A Phase 2, Open-label, Randomized, Multi-arm Study of BGB-A445 in Combination With Investigational Agents in Non-Small Cell Lung Cancer Patients Previously Treated With Anti-PD-(L)1 Antibody
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 35
- Locations
- 33
- Primary Endpoint
- Overall Response Rate
Study Overview
Brief Summary
The main objective of this study was to evaluate the anti-tumor activity of gimistotug (BGB-A445) plus investigational agents in participants with non-small cell lung cancer (NSCLC).
Detailed Description
This study tested whether gimistotug in combination with other agents could help treat participants with non-small cell lung cancer (NSCLC) who were already treated with other anticancer agents, including anti-programmed cell death protein-1 (anti-PD-1) and anti-programmed cell death protein ligand-1 (anti-PD-L1) antibodies and platinum-based chemotherapy. The main goal of this study was to see if gimistotug could increase participant response to treatment, also called the overall response rate.
Only a portion of patients with advanced solid tumors have a durable response to currently available treatments. This represents an unmet medical need to develop improved therapeutic options. Combining immunotherapies with agents having different mechanism of action might improve outcomes for these patients.
This study was designed as a proof of concept to show that gimistotug-based combination treatment may be able to improve responses and clinical benefit in patients with NSCLC. Treatments in all cohorts was administered up to 36 cycles (approximately 2 years) until participants experienced no benefits, too many side effects, or withdrew consent.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Advanced or metastatic NSCLC (nonsquamous or squamous) that is histologically or cytologically confirmed
- •Participants who have received no more than 2 lines of prior systemic therapies which must include anti-programmed cell death protein ligand-1 (anti-PD-(L)1) treatment and a platinum-based chemotherapy administered in combination with, or sequentially before or after the anti-PD-(L)1 treatment
- •At least 1 measurable lesion as defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Adequate organ function as indicated by laboratory values during screening
Exclusion Criteria
- •With mixed small cell lung cancer
- •Has received prior therapy targeting OX40 or any other T-cell agonists
- •Has received prior therapy containing docetaxel and/or ramucirumab for advanced or metastatic NSCLC
- •Has received any Chinese herbal medicine or Chinese patent medicines used to control cancer ≤ 14 days before the first dose of study drug(s)
- •Active leptomeningeal disease or uncontrolled and untreated brain metastasis
- •NOTE: Other criteria may apply
Arms & Interventions
Gimistotug + Docetaxel
Participants received gimistotug and docetaxel 75 mg/m^2 both by intravenous infusion once every 3 weeks until disease progression, intolerable toxicity, withdrawal of informed consent, or other discontinuation criterion were met.
Intervention: Gimistotug (Drug)
Gimistotug + Docetaxel
Participants received gimistotug and docetaxel 75 mg/m^2 both by intravenous infusion once every 3 weeks until disease progression, intolerable toxicity, withdrawal of informed consent, or other discontinuation criterion were met.
Intervention: Docetaxel (Drug)
Gimistotug + BGB-15025
Participants received gimistotug by intravenous infusion once every 3 weeks and BGB-15025 orally once daily during each 3-week cycle until disease progression, intolerable toxicity, withdrawal of informed consent, or other discontinuation criterion were met.
Intervention: Gimistotug (Drug)
Gimistotug + BGB-15025
Participants received gimistotug by intravenous infusion once every 3 weeks and BGB-15025 orally once daily during each 3-week cycle until disease progression, intolerable toxicity, withdrawal of informed consent, or other discontinuation criterion were met.
Intervention: BGB-15025 (Drug)
Outcomes
Primary Outcomes
Overall Response Rate
Time Frame: Response was assessed every 6 weeks for the first 9 months and every 12 weeks thereafter; maximum time on follow-up was up to 13.5 months
Overall response rate (ORR) is defined as the percentage of participants with best overall response (BOR) of a confirmed complete response (CR) or partial response (PR) as assessed by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1. CR is defined as: * Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. * Disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes must be nonpathological in size (\< 10 mm short axis). * No new lesions. PR is defined as: * At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. * Non-progressive disease with regard to non-target lesions, persistence of 1 or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. * No new lesions.
Secondary Outcomes
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From first dose of study drug to 30 days after last dose. Maximum time on treatment was 11.2 months)
- Duration of Response (DOR)(From first dose to the end of study; maximum time on follow-up was up to 13.5 months.)
- Disease Control Rate (DCR)(From first dose to the end of study; maximum time on follow-up was up to 13.5 months)
- Clinical Benefit Rate (CBR)(Assessed from first dose to the end of the study. Response was assessed every 6 weeks for the first 9 months and every 12 weeks thereafter; maximum time on follow-up was up to 13.5 months)
- Serum Concentrations of Gimistotug(Cycle 1 Day 1 0.5 hours post-dose, Cycle 2 Day 1 predose, Cycle 5 Day 1 pre- and 0.5 hours post-dose, Cycle 9 Day 1 Predose, End of Treatment visit (30 days after last dose))
- Number of Participants With Anti-Drug Antibodies to Gimistotug(Up to 30 days following last dose. Maximum time on treatment was 11.2 months.)
- Plasma Concentrations of BGB-15025(Cycle 1 Day 1 2 hours and 4-6 hours post-dose, Cycle 1 Day 8 pre-dose, Cycle 1 Day 15 pre-dose, Cycle 2 Day 1 pre-dose and 2 hours and 4-6 hours post-dose, Cycle 3 Day 1 pre-dose)