Non-small Cell Lung Cancer (NSCLC)
Conditions
Keywords
Oncology, Advanced Non-small Cell Lung Cancer, Inoperable Non-small Cell Lung Cancer, Metastatic, Non-resectable, Epidermal growth factor receptor, EGFR
Brief summary
This study has two parts: dose escalation and dose expansion. The primary objectives are: * For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with osimertinib in the study population * For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle 1 onward). In Dose Expansion, there will be 21-day cycles. The number of treatment cycles is not fixed in this study. Participants will continue study treatment until they decide not to (withdraw consent), their disease gets worse \[progressive disease (PD)\], or side effects become unacceptable (unacceptable toxicity).
Interventions
DRUGDS-1205c
DS-1205c 200 mg capsule
DRUGOsimertinib
Osimertinib 80 mg tablet
Sponsors
Daiichi Sankyo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has histologically or cytologically documented adenocarcinoma NSCLC. 2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation. 3. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011): 1. Historical confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) or 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression (Response Evaluation Criteria in Solid Tumors \[RECIST version 1.1\] or World Health Organization \[WHO\]) while on continuous treatment with an EGFR TKI. 4. Is currently receiving, and is able to discontinue erlotinib, gefinitib, or afatinib; or is currently receiving osimertinib at the prescribed 80 mg dose and is able to interrupt osimertinib. 5. Has been receiving erlotinib, gefitinib, or afatinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period. 6. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib. 7. Has at least one measurable lesion per RECIST version 1.1. 8. Is willing to provide archival tumor tissue from a biopsy performed after progression during treatment with erlotinib, gefitinib, afatinib , or osimertinib OR has at least one lesion not previously irradiated, amenable to core biopsy, and is willing to undergo screening tumor biopsy. 9. Demonstrates absence of EGFR T790M. No EGFR mutation testing is required if treated with osimertinib. 10. Has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, with no deterioration over the previous 2 weeks.
Exclusion criteria
1. Has any evidence of small cell histology, or combined small cell and non-small cell histology, in original tumor biopsy or in screening biopsy performed since progression. 2. Has previously documented evidence of anaplastic lymphoma kinase (ALK) fusion, ROS proto-oncogene 1 (ROS1) fusion, BRAF V600E mutation, rearranged during transfection (RET) rearrangement, human epidermal growth factor receptor 2 (HER2) mutation, or MET exon 14 skipping mutation. No new testing for these genomic alterations is required for Screening. 3. Has received treatment with any of the following: 1. Any cytotoxic chemotherapy, immune checkpoint inhibitor therapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than EGFR TKI), within 14 days of the first dose of study treatment. 2. Immune checkpoint inhibitor therapy within 30 days of first dose of study treatment. 3. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment. 4. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks, or palliative radiation therapy within 2 weeks of the first dose of study drug treatment. 4. Has history of other active malignancy within 3 years prior to enrollment, except: 1. Adequately treated non-melanoma skin cancer OR 2. Superficial bladder tumors (tumor stage a \[Ta\], tumor stage is \[Tis\], tumor stage 1 \[T1\]) OR 3. Curatively treated in situ disease OR 4. Low risk non-metastatic prostate cancer (with Gleason score \< 7, and following local treatment or undergoing active surveillance) 5. Has spinal cord compression or clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (1 week for stereotactic radiotherapy). 6. Presence of retinal disease in the eye that is not due to neovascular age-related macular degeneration (nAMD; eg, significant diabetic retinopathy, glaucomatous retinal atrophy, retinal detachment). 7. Has history of myocardial infarction within the past 6 months. 8. Has symptomatic congestive heart failure (New York Heart Association \[NYHA\] Classes II-IV), unstable angina, or cardiac arrhythmia requiring antiarrhythmic treatment. 9. Has left ventricular ejection fraction (LVEF) \<45% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan. 10. Has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, eg, complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval \>250 milliseconds (ms). 11. Has a mean QT interval corrected using Fridericia's correction (QTcF) prolongation \>470 ms for females and \>450 ms for males in three successive Screening measurements. 12. Unable or unwilling to discontinue concomitant use of drugs that are known to prolong the QT interval. 13. Has any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives. 14. Has any history of interstitial lung disease (pulmonary fibrosis or severe radiation pneumonitis) or is suspected to have such disease by imaging during screening. 15. Has history of pancreatitis within the past 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib | Cycle 0, Day 1 (7-day cycle) to Cycle 1, Day 21 of Dose Escalation (each cycle was 21 days) | A dose-limiting toxicity (DLT) was defined as any TEAE not attributable to disease or disease-related processes that occurred during the DLT-evaluation period (Cycle 0, Day 1 to Cycle 1, Day 21 of Dose Escalation) and was Grade 3 or above, according to NCI-CTCAE Version 5.0. |
| Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Screening; Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 4, 8, and 15; Cycle 2 (21-day cycle), Days 1, 2, and 8; Cycle 3 and beyond (21-day cycles), Day 1; and end-of-treatment, 30 days after last dose, up to 1 year | Treatment-emergent adverse events were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity after the initiating the study drug until 30 days after last dose of the study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year | Progression-free survival is defined as the time from the date of first dose to the earliest date of the first objective documentation of disease progression or death due to any cause. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions. |
| Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib | Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year | Overall survival was defined as the time from the date of first dose to the date of death due to any cause. |
| Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib) | The maximum concentration (Cmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate. |
| Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year | Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined 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. Objective response rate is calculated as the number of participants with best objective response \[complete response (CR) or partial response (PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1\], divided by the number of participants in the analysis population. |
| Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib) | The time to maximum concentration (Tmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate. |
| Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib) | The trough plasma concentration (Ctrough) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate. |
| Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib) | The terminal half-life (t1/2) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate. |
| Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib) | The area under the plasma concentration curve from time 0 until last quantifiable time point (AUClast) and the area under the plasma concentration curve over a dosing interval (AUCtau) of DS-1205c alone and in combination with osimertinib were assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate. |
| Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year | Disease control rate (DCR) is defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined 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. |
Countries
Taiwan
Participant flow
Recruitment details
A total of 13 participants who met all inclusion criteria and no exclusion criteria were enrolled from 10 April 2019 to 04 September 2020 in the study at 7 clinical sites in Taiwan.
Pre-assignment details
In the dose escalation phase, the recommended dose for expansion of DS-1205c in combination with a fixed dose of osimertinib was assessed. The doses of DS-1205c selected for this study were based on nonclinical data and were expressed in doses of DS-1205a (free base).
Participants by arm
| Arm | Count |
|---|---|
| DS-1205c 200 mg + Osimertinib Participants who received DS-1205c 200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle. | 6 |
| DS-1205c 400 mg + Osimertinib Participants who received DS-1205c 400 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 400 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle. | 3 |
| DS-1205c 800 mg + Osimertinib Participants who received DS-1205c 800 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 800 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle. | 3 |
| DS-1205c 1200 mg + Osimertinib Participants who received DS-1205c 1200 mg twice daily (BID) at Cycle 0 monotherapy of a 7-day cycle and DS-1205c 1200 mg BID in combination with 80 mg oral dose of osimertinib daily (QD) at Cycle 1 and beyond of a 21-day cycle. | 1 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Clinical progression | 1 | 0 | 0 | 0 |
| Overall Study | Progressive disease by RECIST version 1.1 | 4 | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | DS-1205c 400 mg + Osimertinib | DS-1205c 800 mg + Osimertinib | DS-1205c 1200 mg + Osimertinib | DS-1205c 200 mg + Osimertinib | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 0 Participants | 4 Participants | 7 Participants |
| Age, Continuous | 73.0 years | 64.0 years | 70 years | 57.5 years | 64.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 1 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 3 participants | 3 participants | 1 participants | 6 participants | 13 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 2 / 6 | 1 / 3 | 2 / 3 | 1 / 1 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib
A dose-limiting toxicity (DLT) was defined as any TEAE not attributable to disease or disease-related processes that occurred during the DLT-evaluation period (Cycle 0, Day 1 to Cycle 1, Day 21 of Dose Escalation) and was Grade 3 or above, according to NCI-CTCAE Version 5.0.
Time frame: Cycle 0, Day 1 (7-day cycle) to Cycle 1, Day 21 of Dose Escalation (each cycle was 21 days)
Population: Dose-limiting toxicities were assessed in the Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DS-1205c 200 mg + Osimertinib | Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib
Treatment-emergent adverse events were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity after the initiating the study drug until 30 days after last dose of the study drug.
Time frame: Screening; Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 4, 8, and 15; Cycle 2 (21-day cycle), Days 1, 2, and 8; Cycle 3 and beyond (21-day cycles), Day 1; and end-of-treatment, 30 days after last dose, up to 1 year
Population: Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Insomnia | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Any TEAEs | 6 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Upper respiratory tract infection | 2 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Urinary tract infection | 2 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Pneumonia | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Anaemia | 0 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Dizziness | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Headache | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Cough | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Dyspnoea | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Haemoptysis | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Vomiting | 3 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Diarrhoea | 0 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Constipation | 2 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Rash | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Fatigue | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Pyrexia | 0 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Alanine aminotransferase increased | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Aspartate aminotransferase increased | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Blood Creatinine Phosphokinase Increased | 0 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Blood Creatinine Increased | 0 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Ejection Fraction Decreased | 0 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Lipase Increased | 0 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Overdose | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Blood Creatinine Increased | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Vomiting | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Blood Creatinine Phosphokinase Increased | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Fatigue | 2 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Headache | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Diarrhoea | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Anaemia | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Ejection Fraction Decreased | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Rash | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Constipation | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Pneumonia | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Overdose | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Lipase Increased | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Cough | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Dizziness | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Urinary tract infection | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Upper respiratory tract infection | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Dyspnoea | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Insomnia | 2 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Any TEAEs | 3 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Alanine aminotransferase increased | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Haemoptysis | 1 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Aspartate aminotransferase increased | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Pyrexia | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Urinary tract infection | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Insomnia | 1 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Dizziness | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Headache | 1 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Blood Creatinine Phosphokinase Increased | 1 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Cough | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Dyspnoea | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Haemoptysis | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Vomiting | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Blood Creatinine Increased | 1 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Diarrhoea | 2 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Constipation | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Rash | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Fatigue | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Ejection Fraction Decreased | 1 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Pyrexia | 2 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Lipase Increased | 1 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Any TEAEs | 3 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Alanine aminotransferase increased | 1 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Upper respiratory tract infection | 1 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Aspartate aminotransferase increased | 1 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Overdose | 2 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Pneumonia | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Anaemia | 1 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Ejection Fraction Decreased | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Aspartate aminotransferase increased | 1 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Insomnia | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Lipase Increased | 1 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Overdose | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Dyspnoea | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Headache | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Any TEAEs | 1 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Anaemia | 1 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Blood Creatinine Phosphokinase Increased | 1 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Pneumonia | 1 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Upper respiratory tract infection | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Constipation | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Blood Creatinine Increased | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Alanine aminotransferase increased | 1 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Rash | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Diarrhoea | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Vomiting | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Cough | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Fatigue | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Dizziness | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Haemoptysis | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Urinary tract infection | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib | Pyrexia | 0 Participants |
Secondary
Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib
The area under the plasma concentration curve from time 0 until last quantifiable time point (AUClast) and the area under the plasma concentration curve over a dosing interval (AUCtau) of DS-1205c alone and in combination with osimertinib were assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
Time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DS-1205c 200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 0: Day 7 | 4818 h*ng/mL | Standard Deviation 1772 |
| DS-1205c 200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 0: Day 7 | 4193 h*ng/mL | Standard Deviation 1514 |
| DS-1205c 200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 2: Day 1 | 4596 h*ng/mL | Standard Deviation 1488 |
| DS-1205c 200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 2: Day 1 | 4445 h*ng/mL | Standard Deviation 1389 |
| DS-1205c 200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 0: Day 1 | 1975 h*ng/mL | Standard Deviation 563 |
| DS-1205c 200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 0: Day 1 | 1916 h*ng/mL | Standard Deviation 530 |
| DS-1205c 400 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 2: Day 1 | 6852 h*ng/mL | Standard Deviation 2716 |
| DS-1205c 400 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 0: Day 1 | 2493 h*ng/mL | Standard Deviation 277 |
| DS-1205c 400 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 0: Day 7 | 6496 h*ng/mL | Standard Deviation 2208 |
| DS-1205c 400 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 0: Day 1 | 2557 h*ng/mL | Standard Deviation 257 |
| DS-1205c 400 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 2: Day 1 | 7117 h*ng/mL | Standard Deviation 2883 |
| DS-1205c 400 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 0: Day 7 | 5716 h*ng/mL | Standard Deviation 1931 |
| DS-1205c 800 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 2: Day 1 | 7640 h*ng/mL | Standard Deviation 2918 |
| DS-1205c 800 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 0: Day 7 | 7385 h*ng/mL | Standard Deviation 4562 |
| DS-1205c 800 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 0: Day 1 | 3002 h*ng/mL | Standard Deviation 1472 |
| DS-1205c 800 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 2: Day 1 | 7220 h*ng/mL | Standard Deviation 2629 |
| DS-1205c 800 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 0: Day 1 | 2891 h*ng/mL | Standard Deviation 1398 |
| DS-1205c 800 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 0: Day 7 | 6972 h*ng/mL | — |
| DS-1205c 1200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 2: Day 1 | 9495 h*ng/mL | — |
| DS-1205c 1200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 0: Day 1 | 5050 h*ng/mL | — |
| DS-1205c 1200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUClast, Cycle 0: Day 7 | 8602 h*ng/mL | — |
| DS-1205c 1200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 2: Day 1 | 10000 h*ng/mL | — |
| DS-1205c 1200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 0: Day 1 | 5255 h*ng/mL | — |
| DS-1205c 1200 mg + Osimertinib | Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib | AUCtau, Cycle 0: Day 7 | 10300 h*ng/mL | — |
Secondary
Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
Disease control rate (DCR) is defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined 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.
Time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Population: Disease control rate was assessed in the Full Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DS-1205c 200 mg + Osimertinib | Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | 2 Participants |
| DS-1205c 400 mg + Osimertinib | Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | 3 Participants |
| DS-1205c 800 mg + Osimertinib | Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | 3 Participants |
| DS-1205c 1200 mg + Osimertinib | Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | 1 Participants |
Secondary
Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib
The maximum concentration (Cmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
Time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DS-1205c 200 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 292 ng/mL | Standard Deviation 94.8 |
| DS-1205c 200 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 544 ng/mL | Standard Deviation 176 |
| DS-1205c 200 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 561 ng/mL | Standard Deviation 191 |
| DS-1205c 400 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 413 ng/mL | Standard Deviation 94 |
| DS-1205c 400 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 845 ng/mL | Standard Deviation 328 |
| DS-1205c 400 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 827 ng/mL | Standard Deviation 299 |
| DS-1205c 800 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 1041 ng/mL | Standard Deviation 460 |
| DS-1205c 800 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 499 ng/mL | Standard Deviation 222 |
| DS-1205c 800 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 921 ng/mL | Standard Deviation 260 |
| DS-1205c 1200 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 703 ng/mL | — |
| DS-1205c 1200 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 1150 ng/mL | — |
| DS-1205c 1200 mg + Osimertinib | Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 1070 ng/mL | — |
Secondary
Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined 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. Objective response rate is calculated as the number of participants with best objective response \[complete response (CR) or partial response (PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1\], divided by the number of participants in the analysis population.
Time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Population: Best overall response was assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DS-1205c 200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Partial response (PR) | 0 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Not evaluable (NE) | 1 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Complete response (CR) | 0 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Progressive disease (PD) | 3 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Stable disease (SD) | 2 Participants |
| DS-1205c 200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Overall response rate (ORR) | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Stable disease (SD) | 3 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Complete response (CR) | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Overall response rate (ORR) | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Partial response (PR) | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Not evaluable (NE) | 0 Participants |
| DS-1205c 400 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Progressive disease (PD) | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Stable disease (SD) | 3 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Complete response (CR) | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Partial response (PR) | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Progressive disease (PD) | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Not evaluable (NE) | 0 Participants |
| DS-1205c 800 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Overall response rate (ORR) | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Partial response (PR) | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Overall response rate (ORR) | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Not evaluable (NE) | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Complete response (CR) | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Progressive disease (PD) | 0 Participants |
| DS-1205c 1200 mg + Osimertinib | Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | Stable disease (SD) | 1 Participants |
Secondary
Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib
Overall survival was defined as the time from the date of first dose to the date of death due to any cause.
Time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Population: Overall survival was assessed in the Full Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DS-1205c 200 mg + Osimertinib | Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib | 46.9 weeks |
| DS-1205c 400 mg + Osimertinib | Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib | NA weeks |
| DS-1205c 800 mg + Osimertinib | Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib | NA weeks |
| DS-1205c 1200 mg + Osimertinib | Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib | NA weeks |
Secondary
Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
Progression-free survival is defined as the time from the date of first dose to the earliest date of the first objective documentation of disease progression or death due to any cause. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions.
Time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Population: Progression-free survival was assessed in the Full Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DS-1205c 200 mg + Osimertinib | Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | 7.1 weeks |
| DS-1205c 400 mg + Osimertinib | Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | NA weeks |
| DS-1205c 800 mg + Osimertinib | Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | 22.0 weeks |
| DS-1205c 1200 mg + Osimertinib | Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib | 12.4 weeks |
Secondary
Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib
The terminal half-life (t1/2) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
Time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Population: The pharmacokinetic parameter of terminal half-life (t1/2) was assessed in the Pharmacokinetic Analysis Set, except for 1 patient (Cohort 1) who did not have an available sample.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DS-1205c 200 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 9.8 hours | Standard Deviation 3.3 |
| DS-1205c 200 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 11.6 hours | Standard Deviation 6.7 |
| DS-1205c 200 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 6.98 hours | Standard Deviation 1.89 |
| DS-1205c 400 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 7.9 hours | Standard Deviation 0.8 |
| DS-1205c 400 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 5.3 hours | Standard Deviation 1 |
| DS-1205c 400 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 7.1 hours | Standard Deviation 1 |
| DS-1205c 800 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 6.9 hours | — |
| DS-1205c 800 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 4.7 hours | Standard Deviation 0.6 |
| DS-1205c 800 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 7.0 hours | Standard Deviation 1.3 |
| DS-1205c 1200 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 11.7 hours | — |
| DS-1205c 1200 mg + Osimertinib | Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 3.3 hours | — |
Secondary
Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib
The time to maximum concentration (Tmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
Time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DS-1205c 200 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 4.1 hours |
| DS-1205c 200 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 4.1 hours |
| DS-1205c 200 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 4.0 hours |
| DS-1205c 400 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 4.0 hours |
| DS-1205c 400 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 4.0 hours |
| DS-1205c 400 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 4.0 hours |
| DS-1205c 800 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 4.0 hours |
| DS-1205c 800 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 3.9 hours |
| DS-1205c 800 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 2.1 hours |
| DS-1205c 1200 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 1 | 6.2 hours |
| DS-1205c 1200 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 3.9 hours |
| DS-1205c 1200 mg + Osimertinib | Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 4.0 hours |
Secondary
Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib
The trough plasma concentration (Ctrough) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
Time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DS-1205c 200 mg + Osimertinib | Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 376 ng/mL | Standard Deviation 143 |
| DS-1205c 200 mg + Osimertinib | Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 359 ng/mL | Standard Deviation 137 |
| DS-1205c 400 mg + Osimertinib | Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 576 ng/mL | Standard Deviation 275 |
| DS-1205c 400 mg + Osimertinib | Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 460 ng/mL | Standard Deviation 219 |
| DS-1205c 800 mg + Osimertinib | Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 688 ng/mL | Standard Deviation 631 |
| DS-1205c 800 mg + Osimertinib | Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 722 ng/mL | Standard Deviation 406 |
| DS-1205c 1200 mg + Osimertinib | Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 0: Day 7 | 816 ng/mL | — |
| DS-1205c 1200 mg + Osimertinib | Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib | Cycle 2: Day 1 | 903 ng/mL | — |