Adenocarcinoma Gastric Stage IV With Metastases, Adenocarcinoma - GEJ
Conditions
Keywords
Human epidermal receptor 2 positive, Unresectable or metastatic, HER2, Prior treatment regimen included trastuzumab
Brief summary
This study will find out if trastuzumab deruxtecan is safe and works for participants with gastric or gastroesophageal junction cancer. They must have human epidermal growth factor receptor 2 (HER2)-positive gastric or gastro-esophageal junction (GEJ) cancer: * that cannot be removed surgically * that has moved to other parts of the body * that got worse during or after treatment that included trastuzumab The study will enroll about 80 participants. Sites will be in North America and the European Union.
Interventions
DRUGTrastuzumab deruxtecan
Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion
Sponsors
AstraZeneca
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
* Men or women ≥18 years old (local regulatory guidelines apply) * Has pathologically documented HER2-positive gastric or GEJ cancer that is unresectable or metastatic, and that progressed during or after treatment regimen containing trastuzumab * Has at least one measurable lesion per RECIST v1.1, as confirmed by investigator review * If of reproductive potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug
Exclusion criteria
* Has had anticancer therapy after first-line treatment regimen containing trastuzumab * Has uncontrolled cardiovascular disease, including any of the following: history of myocardial infarction (MI) within 6 months of first dose or symptomatic congestive heart failure (New York Heart Association Class II to IV), troponin levels consistent with MI as defined according to the manufacturer within 28 days of first dose, or corrected QT interval (QTc) prolongation to \>470 ms (females) or \>450 ms (male) based on screening triplicate 12-lead electrocardiogram (ECG) * Has history of non-infectious interstitial lung disease (ILD)/pneumonitis that required corticosteroid therapy, or current ILD/pneumonitis that cannot be ruled out at screening * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the first dose, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy. * Has pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART) * Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms (Note: participants with clinically inactive brain metastases may be included in the study as well as participants with treated brain metastases who are no longer symptomatic and no longer require treatment with corticosteroids or anticonvulsants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | Up to 16 months (data cut-off) | The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee 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. Confirmed ORR based on ICR is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | Up to 16 months (data cut-off) | Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. |
| Progression-Free Survival (PFS) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | Up to 16 months (data cut-off) | Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. |
| Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | Up to 16 months (data cut-off) | The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment 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. Confirmed ORR based on investigator assessment is reported. |
| Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | Up to 16 months (data cut-off) | Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause. |
| Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | Up to 16 months (data cut-off) | 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 based on independent central review. |
Countries
Belgium, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 79 participants who met all inclusion criteria and no exclusion criteria were enrolled and treated at clinic centers in United States, Spain, Italy, United Kingdom, and Belgium.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Deruxtecan Participants who have centrally confirmed HER2-positive gastric or gastro-esophageal junction cancer treated with trastuzumab deruxtecan by intravenous (IV) infusion every 3 weeks, until progression of disease or withdrawal from treatment for other reasons. | 79 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 15 |
| Overall Study | Clinical Progression | 4 |
| Overall Study | Death | 2 |
| Overall Study | Miscellaneous | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Progressive Disease | 53 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Trastuzumab Deruxtecan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 33 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants |
| Age, Continuous | 58.8 years STANDARD_DEVIATION 11.78 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 69 Participants |
| Region of Enrollment Belgium | 4 participants |
| Region of Enrollment Italy | 20 participants |
| Region of Enrollment Spain | 4 participants |
| Region of Enrollment United Kingdom | 17 participants |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 46 / 79 |
| other Total, other adverse events | 79 / 79 |
| serious Total, serious adverse events | 37 / 79 |
Outcome results
Primary
Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee 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. Confirmed ORR based on ICR is reported.
Time frame: Up to 23 months (data cut-off)
Population: Objective response rate was assessed in the Full Analysis Set at data cut-off date of 08 Nov 2021.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Deruxtecan | Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | 41.8 Percentage of Participants |
Primary
Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee 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. Confirmed ORR based on ICR is reported.
Time frame: Up to 16 months (data cut-off)
Population: Objective response rate was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Deruxtecan | Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | 38.0 Percentage of Participants |
Secondary
Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
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 based on independent central review.
Time frame: Up to 23 months (data cut-off)
Population: Duration of Response (DOR) was assessed in the Full Analysis Set at data cut-off date of 08 Nov 2021.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan | Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | 8.1 months |
Secondary
Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
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 based on independent central review.
Time frame: Up to 16 months (data cut-off)
Population: Duration of Response (DOR) was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan | Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | 8.1 months |
Secondary
Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment 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. Confirmed ORR based on investigator assessment is reported.
Time frame: Up to 23 months (data cut-off)
Population: Objective response rate was assessed in the Full Analysis Set at data cut-off date of 08 Nov 2021.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Deruxtecan | Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | 36.7 Percentage of Participants |
Secondary
Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment 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. Confirmed ORR based on investigator assessment is reported.
Time frame: Up to 16 months (data cut-off)
Population: Objective response rate was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Deruxtecan | Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | 34.2 Percentage of Participants |
Secondary
Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.
Time frame: Up to 16 months (data cut-off)
Population: Overall survival (OS) was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan | Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | NA months |
Secondary
Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.
Time frame: Up to 23 months (data cut-off)
Population: Overall survival (OS) was assessed in the Full Analysis Set at data cut-off date of 08 Nov 2021.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan | Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | 12.1 months |
Secondary
Progression-Free Survival (PFS) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time frame: Up to 23 months (data cut-off)
Population: Progression-free survival (PFS) was assessed in the Full Analysis Set data at cut-off date of 08 Nov 2021
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan | Progression-Free Survival (PFS) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | 5.6 months |
Secondary
Progression-Free Survival (PFS) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time frame: Up to 16 months (data cut-off)
Population: Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan | Progression-Free Survival (PFS) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | 5.5 months |
Secondary
Progression-Free Survival (PFS) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma
Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time frame: Up to 16 months (data cut-off)
Population: Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan | Progression-Free Survival (PFS) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | 5.5 months |