Study of MLN2480 in Participants With Relapsed or Refractory Solid Tumors Followed by a Dose Expansion in Participants With Metastatic Melanoma

An Open-Label, Phase 1, Dose Escalation Study of MLN2480 in Patients With Relapsed or Refractory Solid Tumors Followed by a Dose Expansion Phase in Patients With Metastatic Melanoma

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01425008

Enrollment

149

Registered

2011-08-29

Start date

2011-09-15

Completion date

2018-10-16

Last updated

2020-08-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Melanoma, Metastatic Melanoma, Neoplasm, Solid Tumor

Keywords

Drug Therapy

Brief summary

This is a phase 1, multicenter, nonrandomized, open-label, dose escalation study. The study will be conducted in 2 stages, Dose Escalation and Dose Expansion. The Dose Escalation phase will include participants with solid tumors (including melanoma) who have failed or are not candidates for standard therapies or for whom no approved therapy is available. The Dose Expansion phase will include participants with metastatic melanoma.

Interventions

DRUGMLN2480

Dose Escalation Phase: participants will receive MLN2480 orally in escalating doses every other day or once weekly for three weeks of a 28-day cycle. Participants may continue treatment for additional cycles (up to 12 months) until disease progression, unacceptable toxicity, or the participant discontinues for any other reason. If it is determined that a participant would derive benefit from continued therapy beyond 12 months treatment may continue. Dose Expansion Phase: Participants will take MLN2480 at the maximum tolerated dose orally every other day or once weekly for three weeks of a 28-day cycle until disease progression, unacceptable toxicity, or the participant discontinues for any other reason. The maximum duration of treatment is 1 year unless determined that a participant would derive benefit from continued therapy beyond 12 months.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Informed consent. 2. Male or female participants 18 years or older. 3. Dose Escalation phase: Participants with solid tumors (including melanoma) who have failed or are not candidates for standard therapies of for whom no approved therapy is available. 4. Dose Expansion phase: Metastatic melanoma (locally advanced or metastatic melanoma). 5. Dose Expansion phase: At least 1 measurable lesion which has not been treated previously with radiotherapy. A newly arising lesion in a previously irradiated field is acceptable. 6. For participants undergoing biopsy procedures: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) must be within the normal range. 7. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (\<=) 1. 8. Adequate tissue sample from either archival formalin-fixed paraffin-embedded (FFPE) tumor tissue or new biopsy of tumor. 9. Previous chemotherapy, immunotherapy, and hormone therapy must be completed at least 4 weeks prior to the administration of MLN2480 and radiation must be completed at least 3 weeks prior to the administration of MLN2480; all associated toxicity must be resolved to \<=Grade 1. 10. Expected survival time of at least 3 months in the opinion of the investigator. 11. Participants who do not have hypo- or hyperthyroidism. 12. Ability to swallow and retain oral medication. 13. Female participants who are postmenopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 3 months after the last dose of study drug or agree to practice true abstinence. 14. Male participants who, even if surgically sterilized, agree to practice effective barrier contraception through 3 months after the last dose of alisertib or agree to practice true abstinence.

Exclusion criteria

1. History of any major disease that might interfere with safe protocol participation. 2. Dose Expansion phase: Previous treatment with RAF or MEK inhibitors. 3. Laboratory values as specified in study protocol. 4. Current enrollment in any other investigational treatment study. 5. Evidence of current uncontrolled cardiovascular conditions within the past 6 months. 6. Prior investigational agents for malignant or non-malignant disease within 4 weeks prior to Day 1. 7. Active hepatitis or human immunodeficiency virus (HIV) infection. 8. Active bacterial or viral infection. 9. Female participants who are pregnant or currently breastfeeding. 10. Major surgery within 28 days of Day 1. 11. Refractory nausea and vomiting, malabsorption, or significant bowel or stomach resection. 12. Inability to comply with study requirements. 13. Other unspecified reasons that, in the opinion of the investigator or Millennium, make the participant unsuitable for enrollment.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Baseline up to 30 days after last dose, or start of subsequent therapy, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle=22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle=28 days] in Expansion Phase)	—
Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	Cycle 1 (Cycle length= 22 days [Q2D] and 28 days [QW])	Dose limiting AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Dose limiting AEs were defined as any of the following events: Grade 4 neutropenia for more than 7 days under maximum supportive therapy; febrile neutropenia; platelet counts decreased of Grade 3 requiring platelet transfusion or blood platelet decreased of Grade 4; if Course 2 was not initiated within 14 days due to AE related to the protocol treatment; Grade 3 or higher non-hematologic toxicity that was considered clinically significant, except the following cases, Grade 3 gastrointestinal symptoms that could be controlled with supportive therapy (example, appropriate use of antiemetics, antidiarrheals), and Grade 3 or higher electrolyte abnormalities that were not deemed clinically significant.
Number of Participants With TEAEs Related to Physical Examination Findings	Baseline up to 30 days after last dose, or start of subsequent therapy, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle=22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle=28 days] in Expansion Phase)	—
Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline up to EOSV (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle length =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle length =28 days] in Expansion Phase)	—
Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	Baseline up to 30 days after last dose, or start of subsequent therapy, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle=22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle=28 days] in Expansion Phase)	—
Eastern Cooperative Oncology Group (ECOG) Performance Score	at EOSV (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle length =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle length =28 days] in Expansion Phase)	ECOG performance score was measured on 6 point scale to assess participant's performance status, where: 0 (fully active, able to carry on all pre-disease activities without restriction); 1 (restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work); 2 (ambulatory greater than(\>) 50 percent (%) of waking hours), capable of all self-care, unable to carry out any work activities); 3 (capable of only limited self-care, confined to bed or chair \>50% of waking hours); 4(completely disabled, cannot carry on any self-care, totally confined to bed or chair); 5 (dead). A higher score indicated greater functional impairment.
Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Baseline up to 30 days after last dose, or start of subsequent therapy, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle=22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle=28 days] in Expansion Phase)	—

Secondary

Measure	Time frame	Description
Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, CLr: Renal Clearance for TAK-580	Q2D Cohorts: Cycle1 Days 1 and 21 up to 24 hours post-dose (Cycle1 length= 22 days); QW Cohorts: Cycle2 Days 1 and 22 up to 7 hours post-dose (Cycle 2 length= 28 days)	—
Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Cycle 1 Days 1 and 21 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 22 days)	—
Overall Response Rate (ORR)	Baseline up to EOSV (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle length =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle length =28 days] in Expansion Phase)	ORR was defined as the percentage of participants with complete response (CR) or partial response (PR). The ORR assessment was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (\<) 10 millimeter (mm). PR: was at least a 30% decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.
Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Baseline, Cycle 1 Day 21 (Q2D), and Cycle 1 Day 22 (QW) (Cycle length= 22 days [Q2D] and 28 days [QW])	The extent of phosphorylated extracellular signal-regulated kinase (pERK) staining was assessed in the melanoma expansion cohorts. The level of staining was assessed by a pathologist (semi-H scores) and by quantified image analysis (quant H-scores). The H-score scale used to interpret data from the pathologist rating was as follows: 0 to 99 =low staining; 100 to 199= medium staining; 200 to 300 =high staining. The H-score scale used to interpret data from the quantified image analysis was as followed: 0 to 100 =low staining; 100 to 150= medium staining; 150 to 235= high staining.
Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	Baseline, Cycle 1 Day 21 (Q2D), and Cycle 1 Day 22 (QW) (Cycle length= 22 days [Q2D] and 28 days [QW])	The extent of cleaved poly ADP-ribose polymerase (cPARP) and BIM-1 was assessed in the melanoma expansion cohorts. The level of staining was assessed by quantified image analysis (quant H-scores) and by quantified image analysis (quant H-scores). The H-score scale used to interpret data from the pathologist rating was as follows: 0 to 99= low staining; 100 to 199 =medium staining; 200 to 300 =high staining. The H-score scale used to interpret data from the quantified image analysis was as followed in cPARP: 0 to 70= low staining; 70 to 175 =medium staining; 175 to 240 =high staining; BIM-1: 0 to 128= low staining; 128 to 155 =medium staining; 155 to 229 =high staining.
QW Dose Escalation Phase, AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for TAK-580	Cycle 1 Days 1 and 22 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days)	—
Progression-free Survival (PFS)	Baseline up to the date of first document PD, or death due to any cause, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle =28 days] in Expansion Phase)	PFS was the time from first dose date of study drug to date of the first documentation of confirmed progressive disease (PD) or death, whichever occurred first. The PFS assessment was based on RECIST 1.1. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions. PFS was calculated using Kaplan-Meier estimate and presented with 2-sided 95% confidence interval. Participants with no response assessment were censored at the date of first dose.
Duration of Response (DOR)	From the first documented response (CR or PR) up to the date of first documented PD (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle =28 days] in Expansion Phase)	DOR was assessed from the first documented response (CR or PR) to the date of first documented PD and was censored at the date of the last assessment for responders who died without documented PD and for responders who were still alive and had not progressed. DOR assessment was based on RECIST v1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to \<10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. DOR was calculated using Kaplan-Meier estimate.
Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Escalation (Esc.) and Expansion (Exp.) Q2D: C1D1 and 21 pre-dose and at multiple time points (up to 48 hours [h]) post-dose (C=22 days [Esc. Q2D] and 28 days [Exp. Q2D]); Esc. QW: C1D1 and 22 at multiple time-points (up to168 h) post-dose (C=28 days)	—
Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Escalation and Expansion Q2D Cohorts: C1D21 pre-dose (C=22 days [Escalation Q2D] and 28 days [Expansion Q2D]); Escalation QW Cohorts: C1D22 pre-dose (C= 28 days)	—
Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Escalation (Esc.) and Expansion (Exp.) Q2D: C1D1 and 21 pre-dose and at multiple time points (up to 48 h) post-dose (C=22 days [Esc. Q2D] and 28 days [Exp. Q2D]); Esc. QW: C1D1 and 22 at multiple time-points (up to168 h) post-dose (C=28 days)	—
Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, t1/2z: Terminal Phase Disposition Half-life for TAK-580	Escalation (Esc.) and Expansion (Exp.) Q2D: C1D21 pre-dose and at multiple time points (up to 48 h) post-dose (C=22 days [Esc. Q2D] and 28 days [Exp. Q2D]); Esc. QW: C1D22 at multiple time-points (up to168 h) post-dose (C=28 days)	—

Countries

United Kingdom, United States

Participant flow

Recruitment details

Participants took part in the study at 16 investigative sites in the United States and United Kingdom from 13 September 2011 to 16 October 2018.

Pre-assignment details

Participants with relapsed and refractory solid tumors and metastatic melanoma were enrolled in Dose Escalation Phase and Dose Expansion Phase respectively to receive TAK-580 (MLN2480), once every other day (Q2D) or once weekly (QW). Q2D Dose Expansion Phase, TAK-580 (BRAF+) was discontinued due to sponsor's decision of strategic deprioritization.

Participants by arm

Arm	Count
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle) TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	4
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle) TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	3
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle) TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	3
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle) TAK-580 135 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	3
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle) TAK-580 200 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	7
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle) TAK-580 280 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	7
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle) TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	3
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle) TAK-580 400 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	3
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle) TAK-580 600 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	13
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle) TAK-580 800 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	4
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive) TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.	16
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated) TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF mutation-positive cutaneous melanoma, which in response to previous treatment with RAF inhibitors and/or MEK inhibitors had relapsed following an objective response, failed to demonstrate an objective response and/or could not tolerate such a regimen due to unacceptable toxicity.	8
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive) TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with NRAS mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.	16
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated) TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with NRAS mutation-positive cutaneous melanoma, which in response to previous treatment with MEK inhibitors had relapsed following an objective response, failed to demonstrate an objective response and/or could not tolerate such a regimen due to unacceptable toxicity.	1
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF/NRAS mutation-negative cutaneous melanoma (WT), naive to any prior anticancer therapy except ipilimumab, PD-1, and PDL-1 monoclonal antibodies.	6
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF/NRAS mutation-negative melanoma (WT), who had received at least 1 line of prior anticancer therapy.	11
Q2D Dose Expansion Phase: Pharmacokinetic Cohort TAK-580 200 mg, tablets, orally, on Days 1 through 21 in a 28-days treatment Cycle 1, followed by TAK-580 200 mg, tablets, orally, Q2D in each 28-days treatment cycle from Cycle 2 until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with any advanced solid tumor (excluding lymphoma, but including melanoma) who had failed or were not candidates for standard therapies or for whom no approved therapy was available.	20
Q2D Dose Expansion Phase: TAK-580 (BRAF+) TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF-mutation positive cutaneous melanoma.	2
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive TAK-580 600 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49), in participants with NRAS mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.	19
Total	149

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012	FG013	FG014	FG015	FG016	FG017	FG018
Dose Escalation Phase	Adverse Event	2	0	0	0	0	2	0	0	2	0	0	0	0	0	0	0	0	0	0
Dose Escalation Phase	Other	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Dose Escalation Phase	Progressive Disease	2	3	2	3	5	4	0	2	6	2	0	0	0	0	0	0	0	0	0
Dose Escalation Phase	Symptomatic Deterioration	0	0	1	0	0	0	0	0	2	2	0	0	0	0	0	0	0	0	0
Dose Escalation Phase	Unsatisfactory Therapeutic Response	0	0	0	0	1	0	2	1	1	0	0	0	0	0	0	0	0	0	0
Dose Escalation Phase	Withdrawal by Subject	0	0	0	0	1	1	1	0	1	0	0	0	0	0	0	0	0	0	0
Dose Expansion Phase	Adverse Event	0	0	0	0	0	0	0	0	0	0	2	3	3	0	1	1	5	0	3
Dose Expansion Phase	Lost to Follow-up	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Dose Expansion Phase	Other	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2	0	4
Dose Expansion Phase	Progressive Disease	0	0	0	0	0	0	0	0	0	0	10	4	12	1	5	8	9	2	10
Dose Expansion Phase	Symptomatic Deterioration	0	0	0	0	0	0	0	0	0	0	2	1	0	0	0	1	2	0	1
Dose Expansion Phase	Unsatisfactory Therapeutic Response	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dose Expansion Phase	Withdrawal by Subject	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	1	0	0

Baseline characteristics

Characteristic	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Total	QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)
Age, Continuous	71.0 years STANDARD_DEVIATION 10.1	62.5 years STANDARD_DEVIATION 12.47	66.1 years STANDARD_DEVIATION 11.13	50.5 years STANDARD_DEVIATION 0.71	65.1 years STANDARD_DEVIATION 14.67	67.5 years STANDARD_DEVIATION 8.69	56.7 years STANDARD_DEVIATION 17.24	56.0 years	68.4 years STANDARD_DEVIATION 7.86	58.9 years STANDARD_DEVIATION 16.39	54.6 years STANDARD_DEVIATION 12.44	66.8 years STANDARD_DEVIATION 7.5	57.2 years STANDARD_DEVIATION 9.34	54.7 years STANDARD_DEVIATION 13.58	71.0 years STANDARD_DEVIATION 6.24	65.0 years STANDARD_DEVIATION 4.4	58.7 years STANDARD_DEVIATION 14.77	54.7 years STANDARD_DEVIATION 13.65	56.7 years STANDARD_DEVIATION 10.26	66.3 years STANDARD_DEVIATION 8.33
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	16 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	4 Participants	2 Participants	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants	117 Participants	18 Participants	2 Participants	17 Participants	11 Participants	6 Participants	1 Participants	16 Participants	7 Participants	14 Participants	3 Participants	9 Participants	1 Participants	3 Participants	2 Participants	3 Participants	1 Participants	1 Participants	1 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	16 Participants	1 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants	3 Participants	2 Participants	1 Participants	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	5 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	3 Participants	141 Participants	19 Participants	2 Participants	19 Participants	11 Participants	6 Participants	1 Participants	16 Participants	8 Participants	15 Participants	3 Participants	12 Participants	3 Participants	3 Participants	6 Participants	6 Participants	2 Participants	3 Participants	3 Participants
Region of Enrollment United Kingdom	0 Participants	47 Participants	8 Participants	2 Participants	0 Participants	7 Participants	5 Participants	1 Participants	6 Participants	8 Participants	10 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Region of Enrollment United States	4 Participants	102 Participants	11 Participants	0 Participants	20 Participants	4 Participants	1 Participants	0 Participants	10 Participants	0 Participants	6 Participants	4 Participants	13 Participants	3 Participants	3 Participants	7 Participants	7 Participants	3 Participants	3 Participants	3 Participants
Sex: Female, Male Female	3 Participants	73 Participants	9 Participants	2 Participants	8 Participants	6 Participants	3 Participants	1 Participants	6 Participants	5 Participants	6 Participants	2 Participants	8 Participants	1 Participants	2 Participants	4 Participants	1 Participants	2 Participants	2 Participants	2 Participants
Sex: Female, Male Male	1 Participants	76 Participants	10 Participants	0 Participants	12 Participants	5 Participants	3 Participants	0 Participants	10 Participants	3 Participants	10 Participants	2 Participants	5 Participants	2 Participants	1 Participants	3 Participants	6 Participants	1 Participants	1 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk	EG015 affected / at risk	EG016 affected / at risk	EG017 affected / at risk	EG018 affected / at risk
deaths Total, all-cause mortality	1 / 4	0 / 3	1 / 3	0 / 3	0 / 7	1 / 7	0 / 3	0 / 3	2 / 13	1 / 4	0 / 16	2 / 8	2 / 16	0 / 1	0 / 6	0 / 11	1 / 20	1 / 2	0 / 19
other Total, other adverse events	4 / 4	3 / 3	3 / 3	3 / 3	7 / 7	7 / 7	3 / 3	3 / 3	12 / 13	4 / 4	16 / 16	8 / 8	16 / 16	1 / 1	6 / 6	11 / 11	19 / 20	2 / 2	19 / 19
serious Total, serious adverse events	2 / 4	0 / 3	1 / 3	0 / 3	2 / 7	4 / 7	1 / 3	2 / 3	5 / 13	3 / 4	9 / 16	6 / 8	5 / 16	1 / 1	2 / 6	4 / 11	11 / 20	2 / 2	8 / 19

Outcome results

Primary

Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)

Time frame: Baseline up to EOSV (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle length =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle length =28 days] in Expansion Phase)

Population: The safety population included all participants who received at least 1 dose of study drug (TAK-580). Participants who were evaluable for this measure at given time point were included for the assessment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	87.477 kilogram (kg)	Standard Deviation 15.7794
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	7.167 kilogram (kg)	Standard Deviation 16.0315
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-1.693 kilogram (kg)	Standard Deviation 1.4468
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	72.077 kilogram (kg)	Standard Deviation 8.2162
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	67.375 kilogram (kg)	Standard Deviation 17.3371
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	1.542 kilogram (kg)	Standard Deviation 1.1139
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-0.907 kilogram (kg)	Standard Deviation 1.3698
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	77.717 kilogram (kg)	Standard Deviation 4.1695
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	76.963 kilogram (kg)	Standard Deviation 21.9026
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	0.065 kilogram (kg)	Standard Deviation 1.4543
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-0.544 kilogram (kg)	Standard Deviation 3.1033
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	77.695 kilogram (kg)	Standard Deviation 14.3247
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	69.522 kilogram (kg)	Standard Deviation 17.6937
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	0.272 kilogram (kg)	Standard Deviation 1.6037
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-1.225 kilogram (kg)	Standard Deviation 4.5746
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	73.589 kilogram (kg)	Standard Deviation 13.2534
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-1.868 kilogram (kg)	Standard Deviation 4.8255
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	81.054 kilogram (kg)	Standard Deviation 23.6907
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	80.503 kilogram (kg)	Standard Deviation 15.7401
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-1.270 kilogram (kg)	Standard Deviation 0.0005
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-7.825 kilogram (kg)	Standard Deviation 20.1782
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	95.837 kilogram (kg)	Standard Deviation 30.2887
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-1.700 kilogram (kg)	Standard Deviation 6.2386
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	71.288 kilogram (kg)	Standard Deviation 8.657
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	81.312 kilogram (kg)	Standard Deviation 17.4736
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-3.164 kilogram (kg)	Standard Deviation 3.7607
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	57.100 kilogram (kg)	—
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	75.267 kilogram (kg)	Standard Deviation 15.3231
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-3.225 kilogram (kg)	Standard Deviation 2.9826
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	0.201 kilogram (kg)	Standard Deviation 3.7358
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	72.847 kilogram (kg)	Standard Deviation 23.8439
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	79.624 kilogram (kg)	Standard Deviation 16.6098
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-4.292 kilogram (kg)	Standard Deviation 6.5671
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Change at EOSV	-3.189 kilogram (kg)	Standard Deviation 3.969
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	83.298 kilogram (kg)	Standard Deviation 16.3695
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)	Baseline	67.000 kilogram (kg)	—

Primary

Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)

Dose limiting AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Dose limiting AEs were defined as any of the following events: Grade 4 neutropenia for more than 7 days under maximum supportive therapy; febrile neutropenia; platelet counts decreased of Grade 3 requiring platelet transfusion or blood platelet decreased of Grade 4; if Course 2 was not initiated within 14 days due to AE related to the protocol treatment; Grade 3 or higher non-hematologic toxicity that was considered clinically significant, except the following cases, Grade 3 gastrointestinal symptoms that could be controlled with supportive therapy (example, appropriate use of antiemetics, antidiarrheals), and Grade 3 or higher electrolyte abnormalities that were not deemed clinically significant.

Time frame: Cycle 1 (Cycle length= 22 days [Q2D] and 28 days [QW])

Population: The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	2 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	2 Participants

Primary

Eastern Cooperative Oncology Group (ECOG) Performance Score

ECOG performance score was measured on 6 point scale to assess participant's performance status, where: 0 (fully active, able to carry on all pre-disease activities without restriction); 1 (restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work); 2 (ambulatory greater than(\>) 50 percent (%) of waking hours), capable of all self-care, unable to carry out any work activities); 3 (capable of only limited self-care, confined to bed or chair \>50% of waking hours); 4(completely disabled, cannot carry on any self-care, totally confined to bed or chair); 5 (dead). A higher score indicated greater functional impairment.

Time frame: at EOSV (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle length =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle length =28 days] in Expansion Phase)

Arm	Measure	Value (MEAN)	Dispersion
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Eastern Cooperative Oncology Group (ECOG) Performance Score	1.0 score on a scale	Standard Deviation 0
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Eastern Cooperative Oncology Group (ECOG) Performance Score	1.0 score on a scale	Standard Deviation 1
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Eastern Cooperative Oncology Group (ECOG) Performance Score	1.7 score on a scale	Standard Deviation 1.53
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Eastern Cooperative Oncology Group (ECOG) Performance Score	0.3 score on a scale	Standard Deviation 0.58
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Eastern Cooperative Oncology Group (ECOG) Performance Score	1.3 score on a scale	Standard Deviation 0.49
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Eastern Cooperative Oncology Group (ECOG) Performance Score	1.2 score on a scale	Standard Deviation 0.45
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Eastern Cooperative Oncology Group (ECOG) Performance Score	1.0 score on a scale	Standard Deviation 0
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Eastern Cooperative Oncology Group (ECOG) Performance Score	0.7 score on a scale	Standard Deviation 0.58
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Eastern Cooperative Oncology Group (ECOG) Performance Score	1.0 score on a scale	Standard Deviation 0.47
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Eastern Cooperative Oncology Group (ECOG) Performance Score	1.0 score on a scale	Standard Deviation 0
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Eastern Cooperative Oncology Group (ECOG) Performance Score	0.7 score on a scale	Standard Deviation 0.73
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Eastern Cooperative Oncology Group (ECOG) Performance Score	1.5 score on a scale	Standard Deviation 0.58
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Eastern Cooperative Oncology Group (ECOG) Performance Score	0.6 score on a scale	Standard Deviation 0.9
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Eastern Cooperative Oncology Group (ECOG) Performance Score	0.8 score on a scale	Standard Deviation 0.41
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Eastern Cooperative Oncology Group (ECOG) Performance Score	1.2 score on a scale	Standard Deviation 0.98
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Eastern Cooperative Oncology Group (ECOG) Performance Score	0.6 score on a scale	Standard Deviation 0.74
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Eastern Cooperative Oncology Group (ECOG) Performance Score	0.7 score on a scale	Standard Deviation 0.8
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Eastern Cooperative Oncology Group (ECOG) Performance Score	2.0 score on a scale	—

Primary

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths

Time frame: Baseline up to 30 days after last dose, or start of subsequent therapy, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle=22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle=28 days] in Expansion Phase)

Population: The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	4 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	2 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	1 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	3 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	1 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	3 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	1 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	3 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	2 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	7 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	4 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	7 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	1 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	3 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	1 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	3 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	2 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	5 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	2 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	13 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	1 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	4 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	3 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	16 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	9 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	8 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	2 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	6 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	2 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	5 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	16 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	1 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	1 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	2 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	6 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	11 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	4 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	1 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	11 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	20 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	8 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	19 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	TEAEs	2 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	SAEs	2 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Deaths	1 Participants

Primary

Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings

Population: The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	0 Participants

Primary

Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis

Population: The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	1 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	1 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	1 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	1 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	1 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	1 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	8 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	3 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	2 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	3 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	2 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	3 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	2 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	1 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	1 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	5 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	1 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	1 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	3 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	1 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	1 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	1 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	2 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	5 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	3 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	4 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	1 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	2 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	1 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	6 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	3 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	5 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	3 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	1 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	2 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Carbohydrate tolerance analyses (incl diabetes)	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Platelet analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Digestive enzymes	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Coagulation and bleeding analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Pituitary analyses anterior	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	White blood cell analyses	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Skeletal and cardiac muscle analyses	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Cardiac function diagnostic procedures	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Renal function analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Red blood cell analyses	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Tissue enzyme analyses NEC	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Liver function analyses	2 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis	Mineral and electrolyte analyses	1 Participants

Primary

Number of Participants With TEAEs Related to Physical Examination Findings

Population: The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	1 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	1 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	2 Participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	1 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	1 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	1 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	2 Participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	3 Participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	1 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	2 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight increased	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Related to Physical Examination Findings	Breath sounds abnormal	0 Participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Number of Participants With TEAEs Related to Physical Examination Findings	Weight decreased	0 Participants

Secondary

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, CLr: Renal Clearance for TAK-580

Time frame: Q2D Cohorts: Cycle1 Days 1 and 21 up to 24 hours post-dose (Cycle1 length= 22 days); QW Cohorts: Cycle2 Days 1 and 22 up to 7 hours post-dose (Cycle 2 length= 28 days)

Population: CLr of TAK-580 could not be determined since urine samples were collected for a limited duration during a site visit.

Secondary

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580

Time frame: Escalation (Esc.) and Expansion (Exp.) Q2D: C1D1 and 21 pre-dose and at multiple time points (up to 48 hours [h]) post-dose (C=22 days [Esc. Q2D] and 28 days [Exp. Q2D]); Esc. QW: C1D1 and 22 at multiple time-points (up to168 h) post-dose (C=28 days)

Population: The PK-evaluable population included all participants who had sufficient dosing data and TAK-580 concentration-time data to permit calculation of any TAK-580 parameters. PK-evaluable population where data at specified time points was available.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	140.0 nanogram per milliliter (ng/mL)	Standard Deviation 86.61
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 21	301.5 nanogram per milliliter (ng/mL)	Standard Deviation 61.83
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	393.1 nanogram per milliliter (ng/mL)	Standard Deviation 49.81
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 21	759.7 nanogram per milliliter (ng/mL)	Standard Deviation 138.59
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	921.7 nanogram per milliliter (ng/mL)	Standard Deviation 332.4
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 21	2038.8 nanogram per milliliter (ng/mL)	Standard Deviation 1076.99
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	1048.1 nanogram per milliliter (ng/mL)	Standard Deviation 290.91
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 21	3321.5 nanogram per milliliter (ng/mL)	Standard Deviation 1275.83
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	1933.6 nanogram per milliliter (ng/mL)	Standard Deviation 717.03
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 21	3809.1 nanogram per milliliter (ng/mL)	Standard Deviation 466.85
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 21	4063.1 nanogram per milliliter (ng/mL)	Standard Deviation 782.33
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	2675.2 nanogram per milliliter (ng/mL)	Standard Deviation 1296.95
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 21	4588.4 nanogram per milliliter (ng/mL)	Standard Deviation 700.04
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	2072.8 nanogram per milliliter (ng/mL)	Standard Deviation 287.29
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	2934.0 nanogram per milliliter (ng/mL)	Standard Deviation 690.39
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 22	3135.2 nanogram per milliliter (ng/mL)	Standard Deviation 485.7
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	4459.3 nanogram per milliliter (ng/mL)	Standard Deviation 1475.08
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 22	4739.8 nanogram per milliliter (ng/mL)	Standard Deviation 2902.53
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	6774.3 nanogram per milliliter (ng/mL)	Standard Deviation 1082.79
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 22	6460.2 nanogram per milliliter (ng/mL)	Standard Deviation 1632.31
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 1	1606.9 nanogram per milliliter (ng/mL)	Standard Deviation 670.48
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580	Cycle 1 Day 21	3548.8 nanogram per milliliter (ng/mL)	Standard Deviation 1310.21

Secondary

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580

Time frame: Escalation and Expansion Q2D Cohorts: C1D21 pre-dose (C=22 days [Escalation Q2D] and 28 days [Expansion Q2D]); Escalation QW Cohorts: C1D22 pre-dose (C= 28 days)

Arm	Measure	Group	Value (MEAN)	Dispersion
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 21	178.3 ng/mL	Standard Deviation 42.92
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 21	265.5 ng/mL	Standard Deviation 74.25
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 21	1080.0 ng/mL	Standard Deviation 797.75
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 21	1720.0 ng/mL	Standard Deviation 708.87
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 21	1739.7 ng/mL	Standard Deviation 746.88
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 21	2135.0 ng/mL	Standard Deviation 494
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 21	2700.0 ng/mL	Standard Deviation 1088.94
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 22	270.0 ng/mL	Standard Deviation 108
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 22	898.7 ng/mL	Standard Deviation 618.68
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 22	1216.7 ng/mL	Standard Deviation 841.8
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580	Cycle 1 Day 21	2085.0 ng/mL	Standard Deviation 672.26

Secondary

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, t1/2z: Terminal Phase Disposition Half-life for TAK-580

Time frame: Escalation (Esc.) and Expansion (Exp.) Q2D: C1D21 pre-dose and at multiple time points (up to 48 h) post-dose (C=22 days [Esc. Q2D] and 28 days [Exp. Q2D]); Esc. QW: C1D22 at multiple time-points (up to168 h) post-dose (C=28 days)

Population: PK-evaluable population. t1/2z of TAK-580 could not be determined in cancer participants who were on Q2D regimen with a 48-hour dose interval since the duration of plasma PK sample collection within the dose interval was shorter than the anticipated t1/2z of TAK-580. PK-evaluable population where data at specified time points was available.

Arm	Measure	Group	Value (MEDIAN)
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, t1/2z: Terminal Phase Disposition Half-life for TAK-580	Cycle 1 Day 22	50.22 hour
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, t1/2z: Terminal Phase Disposition Half-life for TAK-580	Cycle 1 Day 22	59.06 hour
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, t1/2z: Terminal Phase Disposition Half-life for TAK-580	Cycle 1 Day 22	69.65 hour
Unknown	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, t1/2z: Terminal Phase Disposition Half-life for TAK-580	Cycle 1 Day 1	— hour
Unknown	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, t1/2z: Terminal Phase Disposition Half-life for TAK-580	Cycle 1 Day 21	— hour

Secondary

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580

Time frame: Escalation (Esc.) and Expansion (Exp.) Q2D: C1D1 and 21 pre-dose and at multiple time points (up to 48 h) post-dose (C=22 days [Esc. Q2D] and 28 days [Exp. Q2D]); Esc. QW: C1D1 and 22 at multiple time-points (up to168 h) post-dose (C=28 days)

Arm	Measure	Group	Value (MEDIAN)
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	3.983 hour
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 21	2.000 hour
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	2.150 hour
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 21	3.050 hour
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	2.033 hour
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 21	4.050 hour
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	3.917 hour
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 21	2.000 hour
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	2.050 hour
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 21	2.992 hour
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 21	2.808 hour
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	4.033 hour
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 21	12.792 hour
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	4.000 hour
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	4.150 hour
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 22	3.150 hour
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	3.150 hour
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 22	3.033 hour
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	3.100 hour
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 22	3.950 hour
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 1	3.108 hour
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580	Cycle 1 Day 21	2.192 hour

Secondary

Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points

The extent of cleaved poly ADP-ribose polymerase (cPARP) and BIM-1 was assessed in the melanoma expansion cohorts. The level of staining was assessed by quantified image analysis (quant H-scores) and by quantified image analysis (quant H-scores). The H-score scale used to interpret data from the pathologist rating was as follows: 0 to 99= low staining; 100 to 199 =medium staining; 200 to 300 =high staining. The H-score scale used to interpret data from the quantified image analysis was as followed in cPARP: 0 to 70= low staining; 70 to 175 =medium staining; 175 to 240 =high staining; BIM-1: 0 to 128= low staining; 128 to 155 =medium staining; 155 to 229 =high staining.

Time frame: Baseline, Cycle 1 Day 21 (Q2D), and Cycle 1 Day 22 (QW) (Cycle length= 22 days [Q2D] and 28 days [QW])

Population: PD-evaluable: all participants who had sufficient dosing and PD data, collected within protocol-specified window of sampling time. Participants who were evaluable for this measure at given time point were included. Data for this measure was not planned to be collected and analyzed for Q2D Dose Expansion Phase: Pharmacokinetic Cohort.

Arm	Measure	Group	Value (MEDIAN)
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Quant H-score	265.0 percent change
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Semi H-score	723.5 percent change
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	cPARP Quant H-score	-100.0 percent change
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Quant H-score	136.0 percent change
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	cPARP Semi H-score	-96.0 percent change
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Semi H-score	64.5 percent change
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Quant H-score	158.0 percent change
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	cPARP Quant H-score	317.5 percent change
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	cPARP Semi H-score	-33.0 percent change
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Semi H-score	64.0 percent change
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Semi H-score	-41.0 percent change
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Quant H-score	-52.5 percent change
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	cPARP Quant H-score	-100.0 percent change
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	cPARP Semi H-score	-11.0 percent change
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	cPARP Semi H-score	-48.0 percent change
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Quant H-score	-23.5 percent change
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	cPARP Quant H-score	-33.5 percent change
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Semi H-score	-17.0 percent change
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Quant H-score	35.5 percent change
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Semi H-score	-3.5 percent change
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points	BIM-1 Quant H-score	960.0 percent change

Secondary

Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points

The extent of phosphorylated extracellular signal-regulated kinase (pERK) staining was assessed in the melanoma expansion cohorts. The level of staining was assessed by a pathologist (semi-H scores) and by quantified image analysis (quant H-scores). The H-score scale used to interpret data from the pathologist rating was as follows: 0 to 99 =low staining; 100 to 199= medium staining; 200 to 300 =high staining. The H-score scale used to interpret data from the quantified image analysis was as followed: 0 to 100 =low staining; 100 to 150= medium staining; 150 to 235= high staining.

Time frame: Baseline, Cycle 1 Day 21 (Q2D), and Cycle 1 Day 22 (QW) (Cycle length= 22 days [Q2D] and 28 days [QW])

Population: Pharmacodynamic (PD)-evaluable: all participants who had sufficient dosing and PD data,collected within protocol-specified window of sampling time.Participants who were evaluable for this measure at given time point were included. Data for this measure was not planned to be collected and analyzed for Q2D Dose Expansion Phase:Pharmacokinetic Cohort.

Arm	Measure	Group	Value (MEDIAN)
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Quant H-score	180.0 percent change
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Semi H-score	-94.5 percent change
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Quant H-score	-93.5 percent change
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Semi H-score	-80.5 percent change
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Quant H-score	-82.0 percent change
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Semi H-score	-70.0 percent change
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Quant H-score	-51.0 percent change
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Semi H-score	-24.5 percent change
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Quant H-score	-15.0 percent change
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Semi H-score	-27.0 percent change
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Quant H-score	-8.0 percent change
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Semi H-score	-12.0 percent change
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Quant H-score	-71.0 percent change
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points	Semi H-score	-23.0 percent change

Secondary

Duration of Response (DOR)

DOR was assessed from the first documented response (CR or PR) to the date of first documented PD and was censored at the date of the last assessment for responders who died without documented PD and for responders who were still alive and had not progressed. DOR assessment was based on RECIST v1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to \<10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. DOR was calculated using Kaplan-Meier estimate.

Time frame: From the first documented response (CR or PR) up to the date of first documented PD (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle =28 days] in Expansion Phase)

Population: Analysis population included only a subset of participants (all responders) with response.

Arm	Measure	Value (MEDIAN)
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Duration of Response (DOR)	NA months
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Duration of Response (DOR)	NA months
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Duration of Response (DOR)	6.0 months
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Duration of Response (DOR)	NA months
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Duration of Response (DOR)	1.5 months

Secondary

Overall Response Rate (ORR)

ORR was defined as the percentage of participants with complete response (CR) or partial response (PR). The ORR assessment was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (\<) 10 millimeter (mm). PR: was at least a 30% decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.

Population: Response-evaluable population included all participants with measurable disease who received any amount of TAK-580 and had at least 1 postbaseline response assessment.

Arm	Measure	Value (NUMBER)
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Overall Response Rate (ORR)	0 percentage of participants
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Overall Response Rate (ORR)	0 percentage of participants
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Overall Response Rate (ORR)	0 percentage of participants
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Overall Response Rate (ORR)	0 percentage of participants
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Overall Response Rate (ORR)	0 percentage of participants
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Overall Response Rate (ORR)	0 percentage of participants
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Overall Response Rate (ORR)	0 percentage of participants
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Overall Response Rate (ORR)	0 percentage of participants
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Overall Response Rate (ORR)	13 percentage of participants
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Overall Response Rate (ORR)	33 percentage of participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Overall Response Rate (ORR)	50 percentage of participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Overall Response Rate (ORR)	17 percentage of participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Overall Response Rate (ORR)	7 percentage of participants
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Overall Response Rate (ORR)	0 percentage of participants
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Overall Response Rate (ORR)	0 percentage of participants
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Overall Response Rate (ORR)	0 percentage of participants
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Overall Response Rate (ORR)	0 percentage of participants
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Overall Response Rate (ORR)	0 percentage of participants
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Overall Response Rate (ORR)	0 percentage of participants

Secondary

Progression-free Survival (PFS)

PFS was the time from first dose date of study drug to date of the first documentation of confirmed progressive disease (PD) or death, whichever occurred first. The PFS assessment was based on RECIST 1.1. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions. PFS was calculated using Kaplan-Meier estimate and presented with 2-sided 95% confidence interval. Participants with no response assessment were censored at the date of first dose.

Time frame: Baseline up to the date of first document PD, or death due to any cause, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle =28 days] in Expansion Phase)

Population: The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Arm	Measure	Value (MEDIAN)
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Progression-free Survival (PFS)	1.4 months
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Progression-free Survival (PFS)	1.4 months
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Progression-free Survival (PFS)	1.4 months
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Progression-free Survival (PFS)	1.4 months
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Progression-free Survival (PFS)	1.5 months
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Progression-free Survival (PFS)	1.2 months
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Progression-free Survival (PFS)	NA months
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Progression-free Survival (PFS)	9.2 months
QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	Progression-free Survival (PFS)	1.5 months
QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	Progression-free Survival (PFS)	1.9 months
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	Progression-free Survival (PFS)	5.7 months
Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	Progression-free Survival (PFS)	2.4 months
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	Progression-free Survival (PFS)	1.8 months
Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	Progression-free Survival (PFS)	0.8 months
Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	Progression-free Survival (PFS)	1.9 months
Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	Progression-free Survival (PFS)	1.8 months
Q2D Dose Expansion Phase: Pharmacokinetic Cohort	Progression-free Survival (PFS)	3.6 months
QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	Progression-free Survival (PFS)	2.3 months
Q2D Dose Expansion Phase: TAK-580 (BRAF+)	Progression-free Survival (PFS)	1.7 months

Secondary

Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580

Time frame: Cycle 1 Days 1 and 21 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 22 days)

Arm	Measure	Group	Value (MEAN)	Dispersion
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 1	4799.7 hournanogram per milliliter (hng/mL)	Standard Deviation 2570.95
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 21	10679.2 hournanogram per milliliter (hng/mL)	Standard Deviation 2571.83
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 1	11019.7 hournanogram per milliliter (hng/mL)	Standard Deviation 655.03
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 21	21007.9 hournanogram per milliliter (hng/mL)	Standard Deviation 3501.86
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 1	30562.8 hournanogram per milliliter (hng/mL)	Standard Deviation 16909.2
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 21	43294.2 hournanogram per milliliter (hng/mL)	Standard Deviation 10403.72
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 1	36061.9 hournanogram per milliliter (hng/mL)	Standard Deviation 8904.4
Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 21	99626.7 hournanogram per milliliter (hng/mL)	Standard Deviation 29090.62
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 1	50946.5 hournanogram per milliliter (hng/mL)	Standard Deviation 10597.12
Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 21	125540.2 hournanogram per milliliter (hng/mL)	Standard Deviation 46299.79
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 1	78993.3 hournanogram per milliliter (hng/mL)	Standard Deviation 23713.6
Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 21	156439.3 hournanogram per milliliter (hng/mL)	Standard Deviation 26263.33
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 21	165002.1 hournanogram per milliliter (hng/mL)	Standard Deviation 19899.97
Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 1	66799.2 hournanogram per milliliter (hng/mL)	Standard Deviation 7656.58
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 1	53522.2 hournanogram per milliliter (hng/mL)	Standard Deviation 17337.54
QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580	Day 21	127026.4 hournanogram per milliliter (hng/mL)	Standard Deviation 38244.03

Secondary

QW Dose Escalation Phase, AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for TAK-580

Time frame: Cycle 1 Days 1 and 22 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days)

Arm	Measure	Group	Value (MEAN)	Dispersion
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	QW Dose Escalation Phase, AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for TAK-580	Day 1	184534.4 h*ng/mL	Standard Deviation 50225.97
Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	QW Dose Escalation Phase, AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for TAK-580	Day 22	199210.4 h*ng/mL	Standard Deviation 57957.62
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	QW Dose Escalation Phase, AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for TAK-580	Day 1	278247.9 h*ng/mL	Standard Deviation 128772.92
Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	QW Dose Escalation Phase, AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for TAK-580	Day 22	339244.8 h*ng/mL	Standard Deviation 149201.72
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	QW Dose Escalation Phase, AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for TAK-580	Day 1	431723.3 h*ng/mL	Standard Deviation 106266.4
Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	QW Dose Escalation Phase, AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for TAK-580	Day 22	477700.2 h*ng/mL	Standard Deviation 86620.19

Source: ClinicalTrials.gov · Data processed: Feb 11, 2026

Study of MLN2480 in Participants With Relapsed or Refractory Solid Tumors Followed by a Dose Expansion in Participants With Metastatic Melanoma

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)

Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)

Eastern Cooperative Oncology Group (ECOG) Performance Score

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths

Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings

Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis

Number of Participants With TEAEs Related to Physical Examination Findings

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, CLr: Renal Clearance for TAK-580

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, t1/2z: Terminal Phase Disposition Half-life for TAK-580

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580

Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points

Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points

Duration of Response (DOR)

Overall Response Rate (ORR)

Progression-free Survival (PFS)

Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580

QW Dose Escalation Phase, AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for TAK-580