Advanced Solid Tumors
Conditions
Keywords
Advanced solid tumors, phase 1, oncology, HER2, Antibody drug conjugate (ADC)
Brief summary
This is an open-label, two-part, multicenter study to evaluate the safety and tolerability of DS-8201a in participants with advanced solid malignant tumors.
Interventions
DRUGDS-8201a (DP1)
DS-8201a to be administered via intravenous (IV) dose. DS-8201a (DP1) was used for the Dose Escalation phase and for Dose expansion Parts 2a, 2b, 2c, and 2d.
DRUGDS-8201a (DP2)
DS-8201a is to be administered via intravenous (IV) dose. DS-8201a (DP2) was used only used for Dose Expansion Part 2e.
DRUGDS-8201a (DP)
DS-8201a (DP) is to be administered via intravenous (IV) dose.
Sponsors
Daiichi Sankyo
AstraZeneca
Daiichi Sankyo Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group performance status( PS) of 0 or 1. * Left Ventricular Ejection Fraction (LVEF) ≥ 50% Part 1: * Advanced/unresectable or metastatic breast cancer or gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2a: * Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. * Treated with ado-trastuzumab emtansine (T-DM1) Part 2b: * Advanced gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. * Treated with trastuzumab Part 2c: * Advanced breast cancer with HER2 low expression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2d: * Satisfy at least one of the following criteria 1. Advanced/unresectable or metastatic solid malignant tumor with HER2 expression other than breast cancer and gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. 2. Advanced/unresectable or metastatic tumor with HER2 mutation that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2e: * Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. * Treated with ado-trastuzumab emtansine (T-DM1) (patients with HER2 overexpression only)
Exclusion criteria
* Has a medical history of symptomatic Congestive Heart Failure (CHF) (NYHA classes II-IV) or serious cardiac arrhythmia. * Has a medical history of myocardial infarction or unstable angina. * Has a QTc prolongation to \> 450 millisecond (ms) in males and \> 470 ms in females. * Has a medical history of clinically significant lung diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | From 6 months postdose of last participant up to 3 years 5 months | Objective response rate (ORR) by independent central review was defined as the proportion of participants who achieve either complete response \[CR\] or partial response \[PR\] per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | From 6 months postdose of last participant up to 3 years 5 months | Best overall response by independent central review was defined as the proportion of participants who achieved either complete response \[CR\], partial response \[PR\], stable disease (SD), progressive disease (PD), or were non-evaluable (NE) as per RECIST v1.1. CR was defined as a disappearance of all target lesions, PR at least a 30% decrease in the sum of diameters of target lesions, and SD as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included 8 participants with salivary/submandibular/parotid gland, 2 breast with HER2-mutation, 2 endometrial, 2 esophageal, 2 Paget's disease, 1 cholangiocarcinoma, 1 extraskeletal myxoide chondrosarcoma, 1 gallbladder, 1 pancreatic, 1 small intestine, 1 uterine cervix, and 1 participant who received 5.4 mg/kg with HER2-low gastric/GEJ cancer. |
| Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | From 6 months postdose of last participant up to 3 years 5 months | Duration of response (DoR) by independent central review was defined as the time between the date of the first complete response (CR) or partial response (PR) until the date of the first documentation of progressive disease (PD) or death due to any cause. CR was defined as a disappearance of all target lesions, PR as at least a 30% decrease in the sum of diameters of target lesions, and PD as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer. |
| Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | From 6 months postdose of last participant up to 3 years 5 months | Time to response (TTR) by independent central review was defined as the time interval between the date of registration until the date at which the criteria were first met for complete response (CR) or partial response (PR). Only participants who achieved CR or PR were included in the TTR analysis. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer. |
| Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | From 6 months postdose of last participant up to 3 years 5 months | Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer. |
| Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | From 6 months postdose of last participant up to 3 years 5 months | Overall survival (OS) by independent central review was defined as the time interval from the date of enrollment to the date of death from any cause. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer. |
| Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | From 6 months postdose of last participant up to 3 years 5 months | Disease control rate (DCR) by independent central review was calculated as the proportion of participants demonstrating complete response (CR), partial response (PR), or stable disease (SD) for a minimum of 6 weeks (±1week) from the first dosing date. CR was defined as a disappearance of all target lesions, PR as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included 8 participants with salivary/submandibular/parotid gland, 2 breast with HER2-mutation, 2 endometrial, 2 esophageal, 2 Paget's disease, 1 cholangiocarcinoma, 1 extraskeletal myxoide chondrosarcoma, 1 gallbladder, 1 pancreatic, 1 small intestine, 1 uterine cervix, and 1 participant who received 5.4 mg/kg with HER2-low gastric/GEJ cancer. |
| Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | Post first dose up to Day 147 | The serum PK parameters Maximum (peak) Observed serum concentration of DS-8201a and its analytes were estimated using standard non-compartmental method. |
| Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | Post first dose up to Day 147 | The serum PK parameters of Time of maximum plasma concentration (Tmax) for DS-8201a and its analytes were estimated using standard non-compartmental methods. |
| Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | Post first dose up to Day 147 | The serum PK parameters of Terminal elimination half-life for DS-8201a and its analytes was estimated using standard non-compartmental methods. |
| Overview of Treatment-emergent Adverse Events | Baseline up to 28 days after the last dose of study drug, up to 3 years 5 months | Treatment-emergent adverse events were graded by Common Terminology Criteria for Adverse Events, v4.03. |
| Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | Post first dose up to Day 147 | The serum PK parameters of DS-8201a and its analytes for area under the concentration-versus-time curve from time 0 to the last quantifiable concentration as calculated by the linear-up log-down trapezoidal method (AUClast) and AUC from time 0 to infinity (AUCinf) elimination rate constant associated with the terminal phase were estimated using standard non-compartmental methods. |
Countries
Japan, United States
Participant flow
Recruitment details
A total of 292 participants who met all inclusion and no exclusion criteria were enrolled at 8 centers in the US and 6 centers in Japan. A total of 27 participants started the Dose Escalation phase and a total of 265 participants in the Dose Expansion phase.
Pre-assignment details
The Dose Escalation was intended to identify the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of DS-8201a with at least 3 participants evaluable for assessment of dose-limiting toxicity per dose level. Since the MTD was not reached, doses of 5.4 mg/kg and 6.4 mg/kg were chosen for evaluation in the Dose Expansion phase.
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg Participants in Cohort 1 received an intravenous 0.8 mg/kg dose of DS-8201a (FL-DP1). | 3 |
| Dose Escalation: Cohort 2, 1.6 mg/kg Participants in Cohort 2 received an intravenous 1.6 mg/kg dose of DS-8201a (FL-DP1). | 3 |
| Dose Escalation: Cohort 3, 3.2 mg/kg Participants in Cohort 3 received an intravenous 3.2 mg/kg dose of DS-8201a (FL-DP1). | 3 |
| Dose Escalation: Cohort 4, 5.4 mg/kg Participants in Cohort 4 received an intravenous 5.4 mg/kg dose of DS-8201a (FL-DP1). | 6 |
| Dose Escalation: Cohort 5, 6.4 mg/kg Participants in Cohort 5 received an intravenous 6.4 mg/kg dose of DS-8201a (FL-DP1). | 6 |
| Dose Escalation: Cohort 6, 8.0 mg/kg Participants in Cohort 6 received an intravenous 8.0 mg/kg dose of DS-8201a (FL-DP1). | 6 |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg Participants with HER2-overexpressing breast cancer received an intravenous 5.4 mg/kg dose of DS-8201a (FL-DP1). | 49 |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg Participants with HER2-overexpressing breast cancer received an intravenous 6.4 mg/kg dose of DS-8201a (FL-DP1). | 62 |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg Participants with HER2-low expressing breast cancer received an intravenous 5.4 mg/kg dose of DS-8201a (FL-DP1). | 20 |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg Participants with HER2-low expressing breast cancer received an intravenous 6.4 mg/kg dose of DS-8201a (FL-DP1). | 33 |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg Participants with HER2-overexpressing gastric or gastroesophageal junction (GEJ) adenocarcinoma received an intravenous 5.4 mg/kg dose of DS-8201a (FL-DP1). | 17 |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg Participants with HER2-overexpressing gastric or gastroesophageal junction (GEJ) adenocarcinoma received an intravenous 6.4 mg/kg dose of DS-8201a (FL-DP1). | 24 |
| Dose Expansion: HER2-expressing NSCLC Tumors Participants with HER2-expressing NSCLC tumors received an intravenous 6.4 mg/kg dose of DS-8201a (FL-DP1). | 18 |
| Dose Expansion: HER2-expressing Colorectal Tumors Participants with HER2-expressing colorectal tumors received an intravenous 6.4 mg/kg dose of DS-8201a (FL-DP1). | 20 |
| Dose Expansion: HER2-expressing Other Solid Tumors Participants with any other HER2-expressing solid tumor other than breast or gastric or any tumor with HER2 mutation received an intravenous 6.4 mg/kg dose of DS-8201a (FL-DP1). | 22 |
| Total | 292 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose Escalation | Adverse Event | 0 | 0 | 0 | 1 | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation | Ongoing | 1 | 0 | 0 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation | Progressive disease per RECIST | 2 | 3 | 3 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Expansion | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 22 | 0 | 11 | 0 | 5 | 2 | 2 | 1 |
| Dose Expansion | Clinical progression | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 12 | 0 | 3 | 2 | 0 | 1 | 3 | 1 |
| Dose Expansion | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 |
| Dose Expansion | Did not receive treatment | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Dose Expansion | Ongoing | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 10 | 11 | 3 | 0 | 0 | 4 | 0 | 6 |
| Dose Expansion | Other | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Dose Expansion | Progressive disease per RECIST | 0 | 0 | 0 | 0 | 0 | 0 | 19 | 17 | 8 | 16 | 13 | 19 | 10 | 13 | 11 |
| Dose Expansion | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Dose Escalation: Cohort 2, 1.6 mg/kg | Dose Escalation: Cohort 3, 3.2 mg/kg | Dose Escalation: Cohort 4, 5.4 mg/kg | Dose Escalation: Cohort 5, 6.4 mg/kg | Dose Escalation: Cohort 6, 8.0 mg/kg | Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Dose Expansion: HER2-expressing NSCLC Tumors | Dose Escalation: Cohort 1, 0.8 mg/kg | Dose Expansion: HER2-expressing Colorectal Tumors | Dose Expansion: HER2-expressing Other Solid Tumors | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 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 |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 4 Participants | 2 Participants | 4 Participants | 16 Participants | 14 Participants | 6 Participants | 8 Participants | 11 Participants | 16 Participants | 6 Participants | 1 Participants | 4 Participants | 6 Participants | 101 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 33 Participants | 48 Participants | 14 Participants | 25 Participants | 6 Participants | 8 Participants | 12 Participants | 2 Participants | 16 Participants | 16 Participants | 191 Participants |
| Age, Continuous | 66.3 years STANDARD_DEVIATION 4.73 | 48.3 years STANDARD_DEVIATION 14.57 | 66.8 years STANDARD_DEVIATION 14.82 | 58.2 years STANDARD_DEVIATION 10.4 | 66.2 years STANDARD_DEVIATION 10.67 | 56.2 years STANDARD_DEVIATION 12.11 | 54.9 years STANDARD_DEVIATION 10.28 | 57.8 years STANDARD_DEVIATION 9.68 | 56.3 years STANDARD_DEVIATION 10.97 | 64.2 years STANDARD_DEVIATION 11 | 66.2 years STANDARD_DEVIATION 8.55 | 57.4 years STANDARD_DEVIATION 15.29 | 59.3 years STANDARD_DEVIATION 7.09 | 59.5 years STANDARD_DEVIATION 9.9 | 58.5 years STANDARD_DEVIATION 10.16 | 58.1 years STANDARD_DEVIATION 11.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 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 | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 6 Participants | 6 Participants | 3 Participants | 25 Participants | 40 Participants | 6 Participants | 23 Participants | 11 Participants | 24 Participants | 9 Participants | 3 Participants | 17 Participants | 14 Participants | 193 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 19 Participants | 19 Participants | 12 Participants | 7 Participants | 5 Participants | 0 Participants | 8 Participants | 0 Participants | 3 Participants | 7 Participants | 83 Participants |
| Region of Enrollment Japan | 3 participants | 3 participants | 6 participants | 6 participants | 3 participants | 19 participants | 37 participants | 4 participants | 22 participants | 12 participants | 24 participants | 8 participants | 3 participants | 17 participants | 13 participants | 180 participants |
| Region of Enrollment United States | 0 participants | 0 participants | 0 participants | 0 participants | 3 participants | 30 participants | 25 participants | 16 participants | 11 participants | 5 participants | 0 participants | 10 participants | 0 participants | 3 participants | 9 participants | 112 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants | 6 Participants | 5 Participants | 48 Participants | 62 Participants | 20 Participants | 33 Participants | 5 Participants | 4 Participants | 13 Participants | 3 Participants | 9 Participants | 9 Participants | 229 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 12 Participants | 20 Participants | 5 Participants | 0 Participants | 11 Participants | 13 Participants | 63 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 3 / 50 | 1 / 66 | 0 / 21 | 0 / 33 | 1 / 19 | 1 / 25 | 5 / 59 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 6 | 6 / 6 | 6 / 6 | 50 / 50 | 66 / 66 | 20 / 21 | 33 / 33 | 19 / 19 | 25 / 25 | 59 / 59 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 6 | 1 / 6 | 1 / 6 | 11 / 50 | 17 / 66 | 3 / 21 | 12 / 33 | 4 / 19 | 7 / 25 | 18 / 59 |
Outcome results
Primary
Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Objective response rate (ORR) by independent central review was defined as the proportion of participants who achieve either complete response \[CR\] or partial response \[PR\] per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Population: ORR was assessed among participants in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 0 percentage of participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 33.3 percentage of participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 0 percentage of participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 83.3 percentage of participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 33.3 percentage of participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 50.0 percentage of participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 51.0 percentage of participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 53.7 percentage of participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 33.3 percentage of participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 39.4 percentage of participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 26.3 percentage of participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 32.0 percentage of participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 55.6 percentage of participants |
| Dose Expansion: HER2-expressing Colorectal Tumors | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 5.0 percentage of participants |
| Dose Expansion: HER2-expressing Other Solid Tumors | Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 30.4 percentage of participants |
Secondary
Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Best overall response by independent central review was defined as the proportion of participants who achieved either complete response \[CR\], partial response \[PR\], stable disease (SD), progressive disease (PD), or were non-evaluable (NE) as per RECIST v1.1. CR was defined as a disappearance of all target lesions, PR at least a 30% decrease in the sum of diameters of target lesions, and SD as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included 8 participants with salivary/submandibular/parotid gland, 2 breast with HER2-mutation, 2 endometrial, 2 esophageal, 2 Paget's disease, 1 cholangiocarcinoma, 1 extraskeletal myxoide chondrosarcoma, 1 gallbladder, 1 pancreatic, 1 small intestine, 1 uterine cervix, and 1 participant who received 5.4 mg/kg with HER2-low gastric/GEJ cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Population: Best overall response was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 3 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 1 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 2 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 1 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 2 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 1 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 1 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 4 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 0 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 0 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 1 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 0 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 1 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 4 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 0 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 0 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 3 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 3 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 0 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 0 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 4 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 2 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 24 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 19 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 2 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 2 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 28 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 28 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 8 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 1 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 0 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 7 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 0 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 3 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 11 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 1 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 13 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 16 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 3 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 0 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 10 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 0 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 5 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 4 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 0 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 7 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 3 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 0 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 1 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 14 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 5 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 10 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 2 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 0 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 1 Participants |
| Dose Expansion: HER2-expressing Colorectal Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 2 Participants |
| Dose Expansion: HER2-expressing Colorectal Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 1 Participants |
| Dose Expansion: HER2-expressing Colorectal Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 15 Participants |
| Dose Expansion: HER2-expressing Colorectal Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 2 Participants |
| Dose Expansion: HER2-expressing Colorectal Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 0 Participants |
| Dose Expansion: HER2-expressing Other Solid Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Non-evaluable | 1 Participants |
| Dose Expansion: HER2-expressing Other Solid Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Progressive disease | 3 Participants |
| Dose Expansion: HER2-expressing Other Solid Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Complete response | 2 Participants |
| Dose Expansion: HER2-expressing Other Solid Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Stable disease | 12 Participants |
| Dose Expansion: HER2-expressing Other Solid Tumors | Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | Partial response | 5 Participants |
Secondary
Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Disease control rate (DCR) by independent central review was calculated as the proportion of participants demonstrating complete response (CR), partial response (PR), or stable disease (SD) for a minimum of 6 weeks (±1week) from the first dosing date. CR was defined as a disappearance of all target lesions, PR as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included 8 participants with salivary/submandibular/parotid gland, 2 breast with HER2-mutation, 2 endometrial, 2 esophageal, 2 Paget's disease, 1 cholangiocarcinoma, 1 extraskeletal myxoide chondrosarcoma, 1 gallbladder, 1 pancreatic, 1 small intestine, 1 uterine cervix, and 1 participant who received 5.4 mg/kg with HER2-low gastric/GEJ cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Population: DCR was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 100.0 percentage of participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 100.0 percentage of participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 66.7 percentage of participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 100.0 percentage of participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 100.0 percentage of participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 100.0 percentage of participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 88.2 percentage of participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 95.5 percentage of participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 85.7 percentage of participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 87.9 percentage of participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 78.9 percentage of participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 88.0 percentage of participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 83.3 percentage of participants |
| Dose Expansion: HER2-expressing Colorectal Tumors | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 80.0 percentage of participants |
| Dose Expansion: HER2-expressing Other Solid Tumors | Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) | 82.6 percentage of participants |
Secondary
Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Duration of response (DoR) by independent central review was defined as the time between the date of the first complete response (CR) or partial response (PR) until the date of the first documentation of progressive disease (PD) or death due to any cause. CR was defined as a disappearance of all target lesions, PR as at least a 30% decrease in the sum of diameters of target lesions, and PD as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Population: DoR was assessed among participants who achieved a CR or PR in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 12.7 months |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 13.6 months |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | NA months |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 10.4 months |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 5.6 months |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 6.9 months |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 10.7 months |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 13.4 months |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | NA months |
Secondary
Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Overall survival (OS) by independent central review was defined as the time interval from the date of enrollment to the date of death from any cause. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Population: OS was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | NA months |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | NA months |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | NA months |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 19.7 months |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 18.9 months |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 26.2 months |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | NA months |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 15.6 months |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 23.4 months |
Secondary
Overview of Treatment-emergent Adverse Events
Treatment-emergent adverse events were graded by Common Terminology Criteria for Adverse Events, v4.03.
Time frame: Baseline up to 28 days after the last dose of study drug, up to 3 years 5 months
Population: Safety events were assessed in the Safety Analysis Set. It was prespecified in the protocol that single patients with unique tumor types would be combined into 1 group for the safety analysis. For the safety overview, TEAEs for HER2-expressing NSCLC, Colorectal, and Other Solid Tumors (excluding 1 HER2-low gastric cancer subject who received 5.4 mg/kg) were combined and reported together.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 3 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 1 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 1 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 0 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 3 Participants |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 3 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 1 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 2 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 0 Participants |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 3 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 2 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 0 Participants |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 0 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 6 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 0 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 3 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 0 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 1 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 6 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 1 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 3 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 2 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 6 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 5 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 2 Participants |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 0 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 1 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 2 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 3 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 4 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 1 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 2 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 6 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 3 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 6 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 1 Participants |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 3 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 2 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 0 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 3 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 1 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 2 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 2 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 3 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 2 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 6 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 6 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 2 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 1 Participants |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 0 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 5 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 5 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 7 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 21 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 15 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 18 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 23 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 3 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 11 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 4 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 50 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 50 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 1 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 4 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 1 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 66 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 42 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 18 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 17 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 18 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 1 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 22 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 28 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 37 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 66 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 11 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 36 Participants |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 21 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 8 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 3 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 0 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 3 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 7 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 0 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 0 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 20 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 2 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 20 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 8 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 0 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 11 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 2 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 20 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 23 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 11 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 13 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 12 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 33 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 9 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 2 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 9 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 8 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 33 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 11 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 2 Participants |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 11 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 8 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 5 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 18 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 5 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 1 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 4 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 0 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 10 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 4 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 9 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 0 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 0 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 19 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 0 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 7 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 9 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 13 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 3 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 11 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 25 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 4 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 25 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 20 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 0 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 16 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 1 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 3 Participants |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 9 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | TEAEs ≥Grade 3 | 37 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose reduction | 14 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | Serious TEAEs (including AEs ending in death) | 18 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with death | 2 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs | 59 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | Drug-related serious TEAEs | 9 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs associated with dose reduction | 13 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | TEAEs associated with discontinuation of drug | 5 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | Treatment-emergent adverse events (TEAEs) | 59 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with dose interruption | 17 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | Related TEAEs associated with drug discontinuation | 5 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | TEAEs associated with dose interruption | 22 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | TEAEs associated with death | 5 Participants |
| Dose Expansion: HER2-expressing NSCLC Tumors | Overview of Treatment-emergent Adverse Events | Drug-related TEAEs ≥Grade 3 | 30 Participants |
Secondary
Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose
The serum PK parameters Maximum (peak) Observed serum concentration of DS-8201a and its analytes were estimated using standard non-compartmental method.
Time frame: Post first dose up to Day 147
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 22.9 ug/mL | Standard Deviation 3.76 |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 36.2 ug/mL | Standard Deviation 4.98 |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 78.2 ug/mL | Standard Deviation 16.1 |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 127 ug/mL | Standard Deviation 17.2 |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 181 ug/mL | Standard Deviation 33.1 |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 221 ug/mL | Standard Deviation 41 |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 126 ug/mL | Standard Deviation 37.7 |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 170 ug/mL | Standard Deviation 53.6 |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 133 ug/mL | Standard Deviation 18.3 |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 155 ug/mL | Standard Deviation 33.2 |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 113 ug/mL | Standard Deviation 30 |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 116 ug/mL | Standard Deviation 21.1 |
| Dose Expansion: HER2-expressing NSCLC Tumors | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 150 ug/mL | Standard Deviation 30.3 |
| Dose Expansion: HER2-expressing Colorectal Tumors | Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose | 155 ug/mL | Standard Deviation 21.4 |
Secondary
Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose
The serum PK parameters of Terminal elimination half-life for DS-8201a and its analytes was estimated using standard non-compartmental methods.
Time frame: Post first dose up to Day 147
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 2.18 days | Standard Deviation 0.671 |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 3.07 days | Standard Deviation 1.22 |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 4.23 days | Standard Deviation 1.24 |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 6.03 days | Standard Deviation 0.603 |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 7.33 days | Standard Deviation 1.64 |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 6.44 days | Standard Deviation 0.793 |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 5.52 days | Standard Deviation 1.23 |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 6.00 days | Standard Deviation 1.22 |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 5.28 days | Standard Deviation 1.49 |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 5.79 days | Standard Deviation 1.01 |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 6.18 days | Standard Deviation 1.18 |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 5.90 days | Standard Deviation 1.57 |
| Dose Expansion: HER2-expressing NSCLC Tumors | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 5.61 days | Standard Deviation 1.29 |
| Dose Expansion: HER2-expressing Colorectal Tumors | Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose | 5.46 days | Standard Deviation 1.02 |
Secondary
Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose
The serum PK parameters of Time of maximum plasma concentration (Tmax) for DS-8201a and its analytes were estimated using standard non-compartmental methods.
Time frame: Post first dose up to Day 147
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 1.95 hours |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 4.03 hours |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 4.12 hours |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 2.02 hours |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 2.06 hours |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 1.97 hours |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 2.00 hours |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 2.08 hours |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 2.16 hours |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 2.00 hours |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 2.03 hours |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 1.95 hours |
| Dose Expansion: HER2-expressing NSCLC Tumors | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 2.02 hours |
| Dose Expansion: HER2-expressing Colorectal Tumors | Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose | 2.05 hours |
Secondary
Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose
The serum PK parameters of DS-8201a and its analytes for area under the concentration-versus-time curve from time 0 to the last quantifiable concentration as calculated by the linear-up log-down trapezoidal method (AUClast) and AUC from time 0 to infinity (AUCinf) elimination rate constant associated with the terminal phase were estimated using standard non-compartmental methods.
Time frame: Post first dose up to Day 147
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 51.7 ug*d/mL | Standard Deviation 13.1 |
| Dose Escalation: Cohort 1, 0.8 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 55.0 ug*d/mL | Standard Deviation 11.9 |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 116 ug*d/mL | Standard Deviation 58.7 |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 121 ug*d/mL | Standard Deviation 58.9 |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 325 ug*d/mL | Standard Deviation 142 |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 340 ug*d/mL | Standard Deviation 150 |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 544 ug*d/mL | Standard Deviation 165 |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 590 ug*d/mL | Standard Deviation 186 |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 1030 ug*d/mL | Standard Deviation 209 |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 901 ug*d/mL | Standard Deviation 155 |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 1100 ug*d/mL | Standard Deviation 259 |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 996 ug*d/mL | Standard Deviation 229 |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 559 ug*d/mL | Standard Deviation 178 |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 602 ug*d/mL | Standard Deviation 203 |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 785 ug*d/mL | Standard Deviation 228 |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 848 ug*d/mL | Standard Deviation 243 |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 589 ug*d/mL | Standard Deviation 145 |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 581 ug*d/mL | Standard Deviation 180 |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 762 ug*d/mL | Standard Deviation 205 |
| Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 693 ug*d/mL | Standard Deviation 178 |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 596 ug*d/mL | Standard Deviation 183 |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 542 ug*d/mL | Standard Deviation 163 |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 563 ug*d/mL | Standard Deviation 151 |
| Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 507 ug*d/mL | Standard Deviation 126 |
| Dose Expansion: HER2-expressing NSCLC Tumors | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 631 ug*d/mL | Standard Deviation 184 |
| Dose Expansion: HER2-expressing NSCLC Tumors | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 683 ug*d/mL | Standard Deviation 209 |
| Dose Expansion: HER2-expressing Colorectal Tumors | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUCinfinity | 753 ug*d/mL | Standard Deviation 118 |
| Dose Expansion: HER2-expressing Colorectal Tumors | Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose | AUClast | 693 ug*d/mL | Standard Deviation 102 |
Secondary
Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Population: PFS was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 13.7 months |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 14.1 months |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | NA months |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 11.1 months |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 4.3 months |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 8.2 months |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 11.3 months |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 4.0 months |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 11.0 months |
Secondary
Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Time to response (TTR) by independent central review was defined as the time interval between the date of registration until the date at which the criteria were first met for complete response (CR) or partial response (PR). Only participants who achieved CR or PR were included in the TTR analysis. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Population: Time to response was assessed among participants who achieved CR or PR in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Cohort 1, 0.8 mg/kg | Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 2.7 months |
| Dose Escalation: Cohort 2, 1.6 mg/kg | Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 2.8 months |
| Dose Escalation: Cohort 3, 3.2 mg/kg | Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 2.6 months |
| Dose Escalation: Cohort 4, 5.4 mg/kg | Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 2.7 months |
| Dose Escalation: Cohort 5, 6.4 mg/kg | Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 1.6 months |
| Dose Escalation: Cohort 6, 8.0 mg/kg | Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 2.2 months |
| Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg | Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 1.4 months |
| Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg | Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 3.0 months |
| Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg | Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases) | 1.6 months |