Advanced or Inoperable Gastric Cancer
Conditions
Keywords
BGB-290, PARP inhibitor, Phase 2, maintenance therapy, gastric cancer, oral treatment, PARALLEL 303, PARALLEL, BGB290303, BGB-290-303
Brief summary
This study enrolled participants with previously-treated advanced or inoperable gastric cancer who have responded to first line platinum therapy into two treatment arms. In Arm A participants received BGB-290; in Arm B participants received placebo. The purpose of this study is to show that BGB-290 (pamiparib) (versus placebo) will improve progression-free survival (PFS) in participants with advanced or inoperable gastric cancer.
Detailed description
This is a double-blind, placebo controlled, randomized multicenter global phase 2 study comparing the efficacy and safety of single agent poly (ADP-ribose) polymerase (PARP) inhibitor BGB-290 to placebo as maintenance therapy in participants with advanced gastric cancer who have responded to first line platinum based chemotherapy. Participants are randomized 1:1 to BGB-290 (Arm A) or placebo (Arm B). Randomization will be stratified by geography, biomarker status, and ECOG performance status. Participants will undergo tumor assessments at screening and then every 8 weeks, or as clinically indicated. Administration of BGB-290 or placebo will continue until disease progression, unacceptable toxicity, death, or another discontinuation criterion is met. After end of treatment, long-term follow-up assessments include tumor imaging every 8 weeks for those participants without disease progression, survival status, and new anticancer therapy.
Interventions
DRUGPamiparib
60 mg orally twice daily
DRUGPlacebo
60 mg orally twice daily
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Age ≥ 18 years. 2. Signed informed consent. 3. Histologically confirmed inoperable locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. 4. Received platinum based first line chemotherapy for ≤ 28 weeks. 5. Confirmed partial response (PR) maintained for ≥ 4 weeks or complete response (CR). 6. Able to be randomized to study ≤ 8 weeks after last platinum dose. 7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. 8. Adequate hematologic, renal and hepatic function. 9. Must be able to provide archival tumor tissue for central biomarker assessment. 10. Females of childbearing potential and non-sterile males must agree to use highly effective methods of birth control throughout the course of study and at least up to 6 months after last dosing. Key
Exclusion criteria
1. Unresolved acute effects of prior therapy ≥ Grade 2. 2. Prior treatment with PARP inhibitor. 3. Chemotherapy, biologic therapy, immunotherapy or other anticancer therapy ≤ 14 days prior to randomization. 4. Major surgery or significant injury ≤ 2 weeks prior to start of study treatment. 5. Diagnosis of myelodysplastic syndrome (MDS) 6. Other diagnoses of significant malignancy 7. Leptomeningeal disease or brain metastasis 8. Inability to swallow capsules or disease affecting gastrointestinal function. 9. Active infections requiring systemic treatment. 10. Clinically significant cardiovascular disease 11. Pregnant or nursing females. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) by Investigator Assessment | Approximately 23 months | PFS is defined as the time from randomization to progressive disease (PD) per Response Evaluation Criteria in Solid Tumors ( RECIST) Version 1.1 by investigator assessment or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time To Second Subsequent Treatment (TSST) | Approximately 23 months | TSST is defined as the time from randomization until the second subsequent anticancer therapy or death after next-line therapy |
| Objective Response Rate (ORR) | Approximately 23 months | ORR is defined as the percentage of participants with a best overall response of Complete Response or Partial Response per RECIST Version 1.1 by investigator assessment |
| Overall Survival (OS) | Approximately 23 months | OS is defined as the time from randomization to death due to any cause. |
| Time To Response | Approximately 23 months | Time to response is defined as the time from randomization to the first documented response of Complete Response or Partial Response per RECIST Version 1.1 by investigator assessment |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From start of study treatment until 30 days after the last study drug intake or initiation of new anticancer therapy, whichever occurs first (up to approximately 4 years and 5.5 months) | — |
| Duration of Response (DOR) | Approximately 23 months | DOR is defined as the time from the first documented confirmed response of Complete Response or Partial Response to progressive disease (PD) per RECIST Version 1.1 by investigator assessment or death due to any cause, whichever occurs first |
Countries
Australia, Belgium, China, Czechia, France, Georgia, Hong Kong, Hungary, Japan, Poland, Russia, Singapore, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled in multiple study centers in Asia, Australia, Europe, and North America.
Participants by arm
| Arm | Count |
|---|---|
| Pamiparib Participants received 60 mg pamiparib orally twice a day until progressive disease, unacceptable toxicity, death, or withdrawal of consent for study treatment, investigator's discretion, start of new anticancer therapy or Sponsor's decision to end the study | 71 |
| Placebo Participants received 60 mg placebo orally twice daily until progressive disease, unacceptable toxicity, death, withdrawal of consent for study treatment, investigator's discretion, start of new anticancer therapy, or Sponsor's decision to end the study | 65 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 42 | 31 |
| Overall Study | Disease progression | 1 | 0 |
| Overall Study | Investigator's Decision | 1 | 2 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Sponsor's Decision | 1 | 0 |
| Overall Study | Sponsor's Decision to End study | 21 | 25 |
| Overall Study | Transfer to Long Term Extension Study | 1 | 0 |
| Overall Study | Treatment Completed | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Placebo | Total | Pamiparib |
|---|---|---|---|
| Age, Continuous | 62.1 years STANDARD_DEVIATION 11.23 | 62.3 years STANDARD_DEVIATION 10.48 | 62.5 years STANDARD_DEVIATION 9.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 9 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 103 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 24 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian | 15 Participants | 35 Participants | 20 Participants |
| Race/Ethnicity, Customized Black or African America | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported/Unknown | 8 Participants | 20 Participants | 12 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 36 Participants | 74 Participants | 38 Participants |
| Sex: Female, Male Female | 20 Participants | 45 Participants | 25 Participants |
| Sex: Female, Male Male | 45 Participants | 91 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 42 / 71 | 31 / 65 |
| other Total, other adverse events | 65 / 71 | 57 / 65 |
| serious Total, serious adverse events | 17 / 71 | 11 / 65 |
Outcome results
Primary
Progression Free Survival (PFS) by Investigator Assessment
PFS is defined as the time from randomization to progressive disease (PD) per Response Evaluation Criteria in Solid Tumors ( RECIST) Version 1.1 by investigator assessment or death due to any cause, whichever occurs first.
Time frame: Approximately 23 months
Population: Intent To Treat (ITT) Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pamiparib | Progression Free Survival (PFS) by Investigator Assessment | 3.7 Months |
| Placebo | Progression Free Survival (PFS) by Investigator Assessment | 2.1 Months |
p-value: =0.1428Log Rank
Secondary
Duration of Response (DOR)
DOR is defined as the time from the first documented confirmed response of Complete Response or Partial Response to progressive disease (PD) per RECIST Version 1.1 by investigator assessment or death due to any cause, whichever occurs first
Time frame: Approximately 23 months
Population: Efficacy Evaluable Analysis Set; Only responders were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pamiparib | Duration of Response (DOR) | 3.6 Months |
| Placebo | Duration of Response (DOR) | NA Months |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From start of study treatment until 30 days after the last study drug intake or initiation of new anticancer therapy, whichever occurs first (up to approximately 4 years and 5.5 months)
Population: Safety Analysis Set includes all participants in the ITT Analysis Set who receive at least one dose of study treatment (pamiparib or placebo).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pamiparib | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With At Least 1 TEAE | 66 Number of participants |
| Pamiparib | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with Serious TEAEs | 17 Number of participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With At Least 1 TEAE | 61 Number of participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with Serious TEAEs | 11 Number of participants |
Secondary
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with a best overall response of Complete Response or Partial Response per RECIST Version 1.1 by investigator assessment
Time frame: Approximately 23 months
Population: Efficacy Evaluable Analysis Set includes all randomized participants who had measurable disease at baseline and had at least one post baseline tumor assessment unless discontinued treatment due to clinical progression or death prior to tumor assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pamiparib | Objective Response Rate (ORR) | 7.7 Percentage of participants |
| Placebo | Objective Response Rate (ORR) | 6.3 Percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Time frame: Approximately 23 months
Population: ITT Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pamiparib | Overall Survival (OS) | 10.2 Months |
| Placebo | Overall Survival (OS) | 12.0 Months |
Secondary
Time To Response
Time to response is defined as the time from randomization to the first documented response of Complete Response or Partial Response per RECIST Version 1.1 by investigator assessment
Time frame: Approximately 23 months
Population: Efficacy Evaluable Analysis Set; Only responders were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pamiparib | Time To Response | 3.68 Months |
| Placebo | Time To Response | 1.87 Months |
Secondary
Time To Second Subsequent Treatment (TSST)
TSST is defined as the time from randomization until the second subsequent anticancer therapy or death after next-line therapy
Time frame: Approximately 23 months
Population: ITT Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pamiparib | Time To Second Subsequent Treatment (TSST) | 9.8 Months |
| Placebo | Time To Second Subsequent Treatment (TSST) | 9.7 Months |