Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06)
Purpose
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.
Condition
- PD-L1-positive, Locally Advanced (Unresectable Stage IIIB/C) or Metastatic NSCLC
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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 1. - 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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 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). |
|
|
Active Comparator Arm B |
Docetaxel, 75 mg/m^2 will be administered via IV infusion, once every 3 weeks (Q3W) (Cycle length=21 days). |
|
Recruiting Locations
More Details
- NCT ID
- NCT06635824
- Status
- Active, not recruiting
- Sponsor
- Genmab
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.