PD-L1-positive, Locally Advanced (Unresectable Stage IIIB/C) or Metastatic NSCLC
Conditions
Keywords
Lung Cancer, Solid Tumors, PD-L1, 4-1BB
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.
Interventions
Sponsors
Genmab
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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. Key
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 5 years | OS is defined as the time from date of randomization to date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 5 years | PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause, whichever occurs first based on response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by the investigator. |
| Confirmed Overall Response Rate (ORR) | Up to approximately 5 years | Confirmed ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on RECIST v1.1 as assessed by the investigator. |
| Duration of Response (DOR) | Up to approximately 5 years | DOR is defined as the time from the onset date of response to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by the investigator. |
| 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) | — |
| 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) | Serum samples will be analyzed using validated, specific, and sensitive immunoassay method. Samples will be screened for ADAs binding to acasunlimab and the titer of confirmed positive/negative samples will be reported. |
| Change From Baseline in Functional Assessment of Cancer Therapy Item GP5 (FACIT-GP5; Version 4) Score | Baseline up to approximately 2 years | Participant's global assessment of treatment tolerability will be assessed by FACIT-GP5. FACIT-GP5 asks participants to rate their agreement with the following statement, "I am bothered by side effects of treatment" in the past 7 days. Responses will be captured on a 5-point Likert scale ranging from 0 to 4 indicating 0 as not at all to 4 as very much bothered by side effects. |
| Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Up to approximately 2 years | The PRO-CTCAE allows participants to report on the frequency, severity, and interference of patient-reported symptoms. For each AE, there are between one and three items to assess the frequency, severity, and/or interference with activities related to that AE. All PRO-CTCAE responses will be scored from 0 to 4 for frequency indicating (0= never to 4= almost constantly), severity (0= none to 4= very severe) and interference with usual or daily activities (0= not at all to 4= very much). |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Croatia, Estonia, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Netherlands, Poland, Portugal, Puerto Rico, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Official
Genmab
Outcome results
None listed