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DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3

DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Itraconazole BID on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3

DS-8201a is provided as a sterile lyophilized powder of DS-8201a in a glass vial, which will be dissolved and administered as an intravenous (IV) solution

DS-8201a

Ritonavir is a OATP1B inhibitor; an antiretroviral tablet for oral administration

Itraconazole is a CYP3A inhibitor; an antifungal tablet for oral administration

Global Clinical Leader

HER2-positive cancer is a cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). HER2 promotes the growth of certain cancer cells. This study will test an experimental drug called DS-8201a that has not been approved by the health authorities yet.

DS-8201a will be tested for safety in patients with advanced solid malignant tumors that test positive for HER2. It also will test how DS-8201a moves within the body (pharmacokinetics).

The expected time from the first subject's enrollment until the last subject's enrollment is approximately 8.5 months. The screening period is 28 days and each cycle of treatment is 21 days.

The data for the primary analysis will cutoff after all subjects have either discontinued the study or completed at least 3 cycles, whichever comes first. After the primary analysis, the main study will be closed and transition to the extension period.

Depending on the preliminary results of Cohort 1, Sponsor may decide whether Cohort 2 will be opened or not.

The number of treatment cycles is not fixed in this study. Subjects who continue to derive clinical benefit from the study drug in the absence of withdrawal of consent, progressive disease (PD), or unacceptable toxicity may continue the study drug.

Study of DS-8201a for Participants With Advanced Solid Malignant Tumors

A Phase 1, Multicenter, Open-label, Single Sequence Crossover Study to Evaluate Drug-drug Interaction Potential of OATP1B/CYP3A Inhibitor on the Pharmacokinetics of DS-8201a in Subjects With HER2-expressing Advanced Solid Malignant Tumors

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody.

Maximum concentration (Cmax) was assessed for MAAA-1181a.

Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) for DS-8201a and total anti-HER2 antibody were assessed.

Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a.

Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for DS-8201a and total anti-HER2 antibody.

Best objective response (BOR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Completed response (CR) was defined as a disappearance of all target lesions, 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 ratio (ORR) was defined as the proportion of participants who achieved CR and PR as assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. 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.

Objective response rate (defined as participants who achieved CR and PR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. 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. ORR with confirmation is Objective Response Rate applying a confirmed response of CR/PR in RECIST version 1.1.

AstraZeneca

Daiichi Sankyo Co., Ltd.

Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily on Day 17 of Cycle 2 until Day 21 of Cycle 3.

Cohort 1: DS-8201a + Ritonavir

Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole BID on Day 17 of Cycle 2 followed by 200 mg QD until Day 21 of Cycle 3.

Cohort 2: DS-8201a + Itraconazole

Total

Age, Continuous

<65 years

≥65 years

Age, Customized

Sex: Female, Male

Race (NIH/OMB)

Demographics were assessed in the Safety Analysis Set.

Contact for Clinical Trial Information

DS-8201a, Cycle 2: DS-8201a only

DS-8201a, Cycle 3: DS-8201a + ritonavir

Total Anti-HER2 antibody, Cycle 2: DS-8201a only

Total Anti-HER2 antibody, Cycle 3: DS-8201a + ritonavir

Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3.

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Treatment With DS-8201a and Ritonavir - Cohort 1

MAAA-1181a, Cycle 2: DS-8201a only

MAAA-1181a, Cycle 3: DS-8201a + ritonavir

Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) For MAAA-1181a Following Treatment With DS-8201a and Ritonavir - Cohort 1

DS-8201a, Cycle 2 (DS-8201a only): AUC17d

DS-8201a, Cycle 2 (DS-8201a only): AUCtau

DS-8201a, Cycle 3 (DS-8201a + ritonavir): AUC17d

DS-8201a, Cycle 3 (DS-8201a + ritonavir): AUCtau

Total Anti-HER2 antibody, Cycle 2 (DS-8201a only): AUC17d

Total Anti-HER2 antibody, Cycle 2 (DS-8201a only): AUCtau

Total Anti-HER2 antibody, Cycle 3 (DS-8201a + ritonavir): AUC17d

Total Anti-HER2 antibody, Cycle 3 (DS-8201a + ritonavir): AUCtau

Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve Following Treatment With DS-8201a and Ritonavir - Cohort 1

MAAA-1181a, Cycle 2 (DS-8201a only): AUC17d

MAAA-1181a, Cycle 2 (DS-8201a only): AUCtau

MAAA-1181a, Cycle 3 (DS-8201a + ritonavir): AUC17d

MAAA-1181a, Cycle 3 (DS-8201a + ritonavir): AUCtau

Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve of MAAA-1181a Following Treatment With DS-8201a and Ritonavir - Cohort 1

Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole twice daily (BID) on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3.

Cohort 1: DS-8201a + Itraconazole

Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Treatment With DS-8201a and Itraconazole - Cohort 2

Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Treatment With DS-8201a and Itraconazole - Cohort 2

Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve Following Treatment With DS-8201a and Itraconazole - Cohort 2

Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve of MAAA-1181a Following Treatment With DS-8201a and Itraconazole - Cohort 2

Complete response (CR)

Partial response (PR)

Stable disease (SD)

Non-CR/Non-PR

Progressive disease (PD)

Non evaluable

Response was assessed in the Efficacy Analysis Set.

Spots Global Cancer Trial Database for unresectable or metastatic solid malignant tumors