Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Irinotecan

Antibodies

Paclitaxel

Albumin-Bound Paclitaxel

Immunoglobulins

Mitogens

Trastuzumab

Trastuzumab deruxtecan

Immunoconjugates

Immunologic Factors

Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease has progressed on two prior regimens, will receive DS-8201a once every 3 weeks.

Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease has progressed on two prior regimens, will receive monotherapy prescribed by the physician before enrollment.

A maximum of 20 non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma will receive DS-8201a once every three weeks.

A maximum of 20 non-randomized patients with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma will receive DS-8201a once every 3 weeks.

DS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration.

DS-8201a

Either:

Irinotecan monotherapy (Starting dosage and usage is 150 mg/m2 biweekly, with dose reduction permitted)

Paclitaxel monotherapy (Starting dosage and usage is 80 mg/m2 weekly, with dose reduction permitted)

Physician's Choice

Global Clinical Leader

The primary purpose of this trial is to compare the efficacy and safety of DS-8201a and physician's choice treatment in HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma patients who have progressed on two prior treatment regimens including fluoropyrimidine agent, platinum agent, and trastuzumab.

Two randomized investigative arms will run in parallel (DS-8201a and Physician's Choice), with participants who have disease progression after two previous regimens.

Two non-randomized exploratory arms will run with HER2 treatment-naive participants.

DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]

A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

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/

The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by independent central imaging review (ICR) based on 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. Unconfirmed ORR (not confirmed by ICR) and confirmed ORR (confirmed by ICR) are reported.

The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by independent central imaging review (ICR) based on RECIST version 1.1. 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 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. Unconfirmed BOR (not confirmed by ICR) and confirmed BOR (confirmed by ICR) are reported.

Duration of survival follow-up (months) was defined as the date of last contact - date of randomization/ registration + 1.Overall Survival (OS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the date of death due to any cause.

Progression-free survival (PFS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.

Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR was measured for responding subjects (PR or CR) only.

Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per RECIST v1.1, 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.

The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Independent Central Review (ICR) based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on RECIST version 1.1. 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 SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions). Confirmed ORR and BOR (confirmed by ICR) are reported.

Time to treatment failure (TTF) was defined as the time from the date of randomization (the date of the registration for Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD), death due to any cause, or treatment discontinuation.

The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on RECIST version 1.1. 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 SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions). Unconfirmed ORR and BOR (not confirmed by Investigator) and confirmed ORR and BOR (confirmed by Investigator) are reported.

Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.

Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.

Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.

Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.

Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The time to maximum serum concentration (Tmax) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.

Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Terminal elimination half-life (t1/2) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.

A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug. Serious adverse events (SAEs) with an onset or worsening 48 days or more after the last dose of study drug, if considered related to the study treatment, are also TEAEs.

A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.

AstraZeneca

Daiichi Sankyo Co., Ltd.

A TEAE is defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug. Serious adverse events (SAEs) with an onset or worsening 48 days or more after the last dose of study drug, if considered related to the study treatment, are also TEAEs.

Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks.

Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment.

Physician's Choice Irinotecan

Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment.

Physician's Choice Paclitaxel

Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment.

Physician's Choice Overall

Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks.

Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a

Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.

Exploratory: Naïve HER2 IHC 1+, DS-8201a

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

South Korea

Japan

Region of Enrollment

Baseline and demographic characteristics were assessed in the Full Analysis Set.

Contact for Clinical Trial Information

Unconfirmed ORR, 25 months (DCO: Nov 8, 2019)

Unconfirmed ORR, 36 months (DCO: Dec 11, 2020)

Confirmed ORR, 25 months (DCO: Nov 8, 2019)

Confirmed ORR, 36 months (DCO: Dec 11, 2020)

Objective response rate was assessed in the Primary Cohort in the Intent-to-Treat Analysis Set.

Percentage of Participants With Objective Response Rate Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

Unconfirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)

Unconfirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)

Unconfirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)

Unconfirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)

Unconfirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)

Unconfirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)

Unconfirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)

Unconfirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)

Unconfirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019)

Unconfirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020)

Confirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)

Confirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)

Confirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)

Confirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)

Confirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)

Confirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)

Confirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)

Confirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)

Confirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019)

Confirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020)

Best overall response was assessed in the Primary Cohort in the Intent-to-Treat Analysis Set.

Percentage of Participants With Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

Duration of survival follow up, 25 months (DCO: Nov 8, 2019)

Duration of survival follow up, 36 months (DCO: Dec 11, 2020)

Overall survival, 25 months (DCO: Nov 8, 2019)

Overall survival, 36 months (DCO: Dec 11, 2020)

Duration of survival and overall survival were assessed in the Intent-to-Treat Analysis Set.

Overall Survival Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

PFS, 25 months (DCO: Nov 8, 2019)

PFS, 36 months (DCO: Dec 11, 2020)

Progression-free survival (PFS) was assessed in the Intent-to-Treat Analysis Set.

Progression-Free Survival Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

Unconfirmed Duration of response (DOR), 25 months (DCO: Nov 8, 2019)

Unconfirmed Duration of response (DOR), 36 months (DCO: Dec 11, 2020)

Confirmed Duration of response (DOR), 25 months (DCO: Nov 8, 2019)

Confirmed Duration of response (DOR), 36 months (DCO: Dec 11, 2020)

Duration of response (DOR) was assessed in the Full Analysis Set.

Duration of Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set)

DCR, 25 months (DCO: Nov 8, 2019)

DCR, 36 months (DCO: Dec 11, 2020)

Disease control rate (DCR) was assessed in the Intent-to-Treat Set.

Disease Control Rate With and Without Confirmation by Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

Confirmed Objective response rate (ORR), 25 months (DCO: Nov 8, 2019)

Confirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020)

Inevaluable, 25 months (DCO: Nov 8, 2019)

Inevaluable, 36 months (DCO: Dec 11, 2020)

Best overall response was assessed in the Exploratory Cohorts in the Intent-to-Treat Analysis Set.

Objective Response Rate and Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

TTF, 25 months (DCO: Nov 8, 2019)

TTF, 36 months (DCO: Dec 11, 2020)

Time to treatment failure (TTF) was assessed in the Full Analysis Set.

Time to Treatment Failure Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set)

Unconfirmed Objective response rate (ORR), 25 months (DCO: Nov 8, 2019)

Unconfirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020)

Objective response rate (ORR) and best overall response (BOR) were assessed in the Response Evaluable Set.

Objective Response Rate and Best Overall Response Based on Investigator Assessment Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Response Evaluable Set)

Cmax: DS-8201a, Cycle 1

Cmax: DS-8201a, Cycle 3

Cmax: Total Anti-HER2 antibody, Cycle 1

Cmax: Total Anti-HER2 antibody, Cycle 3

Ctrough: DS-8201a, Cycle 1

Ctrough: DS-8201a, Cycle 3

Ctrough: Total Anti-HER2 antibody, Cycle 1

Ctrough: Total Anti-HER2 antibody, Cycle 3

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a

Cmax: MAAA-1181a, Cycle 1

Cmax: MAAA-1181a, Cycle 3

Ctrough: MAAA-1181a, Cycle 1

Ctrough: MAAA-1181a Cycle 3

Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of MAAA-1181 Following Treatment With DS-8201a

AUClast: DS-8201a, Cycle 1

AUClast: DS-8201a, Cycle 3

AUClast: Total Anti-HER2 antibody, Cycle 1

AUClast: Total Anti-HER2 antibody, Cycle 3

AUC21d: DS-8201a, Cycle 1

AUC21d: DS-8201a, Cycle 3

AUC21d: Total Anti-HER2 antibody, Cycle 1

AUC21d: Total Anti-HER2 antibody, Cycle 3

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. No patient samples were collected or analyzed for AUClast DS-8201a and total anti-HER2 antibody for Cycle 3 as AUClast was planned to be assessed only for Cycle 1.

Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a

AUClast: MAAA-1181a, Cycle 1

AUClast: MAAA-1181a, Cycle 3

AUC21d: MAAA-1181a, Cycle 1

AUC21d: MAAA-1181a, Cycle 3

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. No patient samples were collected or analyzed for MAAA-1181a for Cycle 3 as AUClast was planned to be assessed only for Cycle 1.

Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of MAAA-1181 Following Treatment With DS-8201a

DS-8201a, Cycle 1

DS-8201a, Cycle 3

Total Anti-HER2 antibody, Cycle 1

Total Anti-HER2 antibody, Cycle 3

MAAA-1181a, Cycle 1

MAAA-1181a, Cycle 3

Pharmacokinetic Parameter of Time to Maximum Serum Concentration (Tmax) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a

Pharmacokinetic parameters were assessed in patients with available data in the Pharmacokinetic Analysis Set.

Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a

Any TEAE, 25 months (DCO: Nov 8, 2019)

Any TEAE, 36 months (DCO: Dec 11, 2020)

Drug-related TEAEs, 25 months (DCO: Nov 8, 2019)

Drug-related TEAEs, 36 months (DCO: Dec 11, 2020)

Serious TEAEs, 25 months (DCO: Nov 8, 2019)

Serious TEAEs, 36 months (DCO: Dec 11, 2020)

Drug-related serious TEAEs, 25 months (DCO: Nov 8, 2019)

Drug-related serious TEAEs, 36 months (DCO: Dec 11, 2020)

TEAEs associated with drug withdrawn, 25 months (DCO: Nov 8, 2019)

TEAEs associated with drug withdrawn, 36 months (DCO: Dec 11, 2020)

Drug-related TEAEs associated with drug withdrawn, 25 months (DCO: Nov 8, 2019)

Drug-related TEAEs associated with drug withdrawn, 36 months (DCO: Dec 11, 2020)

TEAEs associated with dose reduced, 25 months (DCO: Nov 8, 2019)

TEAEs associated with dose reduced, 36 months (DCO: Dec 11, 2020)

Drug-related TEAEs associated with dose reduced, 25 months (DCO: Nov 8, 2019)

Drug-related TEAEs associated with dose reduced, 36 months (DCO: Dec 11, 2020)

TEAEs associated with drug interrupted, 25 months (DCO: Nov 8, 2019)

TEAEs associated with drug interrupted, 36 months (DCO: Dec 11, 2020)

Adverse events were assessed in the Safety Analysis Set.

Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. (Safety Analysis Set)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]	NCT03329690	Neoplasm, Gastr...	DS-8201a Physician's Cho...	20 Years -	Daiichi Sankyo
DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]	NCT03329690	Neoplasm, Gastr...	DS-8201a Physician's Cho...	20 Years -	Daiichi Sankyo

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