A Prospective, Open-Label, Randomized, Phase 3 Trial of Acasunlimab (GEN1046) in Combination With Pembrolizumab Versus Docetaxel in Subjects With PD-L1 Positive Metastatic Non-Small Cell Lung Cancer After Treatment With a PD-1/PD-L1 Inhibitor and Platinum-Containing Chemotherapy (ABBIL1TY NSCLC-06)
Overview
- Phase
- Phase 3
- Intervention
- Acasunlimab
- Conditions
- Not specified
- Sponsor
- Genmab
- Enrollment
- 191
- Locations
- 279
- Primary Endpoint
- Overall Survival (OS)
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief Summary
This is a multicenter, randomized, open-label, international, Phase 3 trial to evaluate the efficacy and safety of acasunlimab in combination with pembrolizumab versus docetaxel (standard of care) in participants with locally advanced (unresectable stage IIIB/C) or programmed death ligand 1 (PD-L1)-positive metastatic non-small cell lung cancer (NSCLC) who have been treated with programmed cell death protein 1 (PD-1)/PD-L1 inhibitor and platinum-containing chemotherapy, administered either in combination or sequentially in the locally advanced (unresectable stage IIIB/C) or metastatic setting.
Detailed Description
The goal of this trial is to determine the efficacy and safety of acasunlimab (an experimental antibody also known as GEN1046 or DuoBody® PDL1x4-1BB) in combination with pembrolizumab (an antibody known as KEYTRUDA®) compared to that of docetaxel (a standard of care chemotherapy). During the trial, the participant's quality of life will also be evaluated using industry-standard scales of measurement. To be eligible, participants must have: 1. non-small cell lung cancer that are locally advanced, unresectable stage IIIB/C or has metastasized (spread) 2. tumors that are positive for the PD-L1 protein (a biomarker that may be predictive of response to therapy) 3. been previously treated with a PD-1/PD-L1-inhibitor and a platinum-containing cancer therapy administered in combination or sequentially (irrespective of the order). Other eligibility criteria will also apply. Participants will be assigned to 1 of 2 active therapies, also known as treatment arms, as follows: * Acasunlimab (100 milligrams \[mg\]) and pembrolizumab (400 mg) once every 6 weeks (Q6W), or * Docetaxel 75 milligrams per meter squared (mg/m\^2) once every 3 weeks (Q3W). The estimated trial duration for a participant will vary but may be up to 5 years, consisting of: * An optional 3-month pre-screening period * A 28-day screening period * Up to 2 years of treatment * A 90-day safety follow-up period * Post-treatment follow-up.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant has histologically or cytologically confirmed locally advanced (unresectable stage IIIB/C) or metastatic NSCLC (stage IV) with known subtype.
- •Participant has progressed radiographically on or after receiving:
- •One prior line of therapy (PD-1/PD-L1 inhibitor and platinum-based chemotherapy concomitantly) in the locally advanced (unresectable stage IIIB/C) or metastatic disease setting; OR
- •No more than 2 prior lines of therapy (PD-1/PD-L1 inhibitor and platinum-based chemotherapy sequentially, irrespective of the order) in the locally advanced (unresectable stage IIIB/C) or metastatic disease setting.
- •Participant must have positive tumor PD-L1 expression (tumor cells ≥1%) determined prospectively on a tumor sample from the locally advanced (unresectable stage IIIB/C) or metastatic setting at a sponsor-designated central laboratory.
- •Participant has measurable disease according to RECIST v1.1 as assessed by the investigator at baseline.
- •Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 within 7 days of Cycle 1 Day
- •Participant has a life expectancy of ≥3 months.
- •Participant must have adequate organ and bone marrow function, per laboratory test results within 7 days of trial treatment.
Exclusion Criteria
- •Documentation of known targetable epidermal growth factor receptor (EGFR) sensitizing mutations, anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), ROS proto-oncogene 1; receptor tyrosine kinase (ROS1) rearrangement, Kirsten rat sarcoma virus (KRAS), B-Raf proto-oncogene (BRAF) mutations, and MET proto-oncogene; receptor tyrosine kinase (MET) exon 14 skipping mutations/MET amplification. NOTE: MET amplification testing is optional based on local availability of the test.
- •Participants with known KRAS/BRAF mutations are eligible for the trial if they do not have access to targeted therapies.
- •Participants with newly identified, untreated or unstable or symptomatic central nervous system (CNS) metastases or history of carcinomatous meningitis.
- •Prior treatment with docetaxel for NSCLC.
- •Prior treatment with a 4-1BB (CD137) targeted agent, any type of antitumor vaccine, autologous cell immunotherapy, or any unapproved immunotherapy.
- •Treatment with an anticancer agent within 28 days prior to the first dose of trial treatment.
- •Note: Other protocol-defined inclusion and exclusion criteria may apply.
Arms & Interventions
Arm A
Acasunlimab, 100 mg and pembrolizumab, 400 mg will be administered via intravenous (IV) infusion, once every 6 weeks (Q6W) (Cycle length=42 days).
Intervention: Acasunlimab
Arm A
Acasunlimab, 100 mg and pembrolizumab, 400 mg will be administered via intravenous (IV) infusion, once every 6 weeks (Q6W) (Cycle length=42 days).
Intervention: Pembrolizumab
Arm B
Docetaxel, 75 mg/m\^2 will be administered via IV infusion, once every 3 weeks (Q3W) (Cycle length=21 days).
Intervention: Docetaxel
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Up to approximately 5 years
OS is defined as the time from date of randomization to date of death due to any cause.
Secondary Outcomes
- Progression-Free Survival (PFS)(Up to approximately 5 years)
- Confirmed Overall Response Rate (ORR)(Up to approximately 5 years)
- Duration of Response (DOR)(Up to approximately 5 years)
- Number of Participants With Adverse Events (AEs)(From first dose until the end of the study (approximately 5 years))
- Time to Treatment Discontinuation Due to AE(From first dose until the end of the study (approximately 5 years))
- Change From Baseline in Functional Assessment of Cancer Therapy Item GP5 (FACIT-GP5; Version 4) Score(Baseline up to approximately 2 years)
- Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to approximately 2 years)
- Plasma Concentration of Acasunlimab(Predose and postdose at multiple timepoints in Cycles 1-4 (Cycle length=42 days))
- Number of Participants With Anti-drug Antibodies (ADAs) to Acasunlimab(Predose and postdose at multiple timepoints in Cycles 1-4 (Cycle length=42 days))