Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06)
- Conditions
- PD-L1-positive Metastatic NSCLC
- Interventions
- Registration Number
- NCT06635824
- Lead Sponsor
- Genmab
- 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 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 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:
1. must have lung cancer that has metastasized (spread)
2. have tumors that are positive for the PD-L1 protein (a biomarker that may be predictive of response to therapy)
3. will have been previously treated with a PD-1/PD-L1-inhibitor and a platinum-containing cancer therapy administered in combination or sequentially.
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 mg) and pembrolizumab (400 mg) once every 6 weeks (Q6W), or
* Docetaxel 75 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 56-day 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 702
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Participant has histologically or cytologically confirmed metastatic NSCLC (stage IV).
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Participant has progressed on or after receiving:
- One prior line of therapy (PD-1/PD-L1 inhibitor and platinum-based chemotherapy concomitantly) in the 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 metastatic disease setting.
-
Participant must have positive tumor PD-L1 expression (tumor cells ≥1%) determined prospectively on a tumor sample from the metastatic setting at a sponsor-designated central laboratory.
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Participant has measurable disease according to RECIST v1.1 as assessed by the investigator at baseline.
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Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 within 7 days of Cycle 1 Day 1.
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Participant has a life expectancy of ≥3 months.
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Participant must have adequate organ and bone marrow function, per laboratory test results within 7 days of trial treatment.
Key
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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), BRAF mutations, and 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 approved targeted therapies.
-
Participants with newly identified or known unstable or symptomatic central nervous system (CNS) metastases or history of carcinomatous meningitis.
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Prior treatment with docetaxel for NSCLC.
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Prior treatment with a 4-1BB (CD137) targeted agent, any type of antitumor vaccine, autologous cell immunotherapy, or any unapproved immunotherapy.
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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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Acasunlimab Acasunlimab, 100 mg and pembrolizumab, 400 mg will be administered via intravenous (IV) infusion, once every 6 weeks (Q6W) (Cycle length=42 days). Arm A Pembrolizumab Acasunlimab, 100 mg and pembrolizumab, 400 mg will be administered via intravenous (IV) infusion, once every 6 weeks (Q6W) (Cycle length=42 days). Arm B Docetaxel Docetaxel, 75 mg/m\^2 will be administered via IV infusion, once every 3 weeks (Q3W) (Cycle length=21 days).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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) Plasma Concentration of Acasunlimab Predose and postdose at multiple timepoints in Cycles 1-4, then every other cycle starting Cycle 5 (Cycle length=42 days) Number of Participants With Anti-drug Antibodies (ADAs) to Acasunlimab Up to approximately 5 years 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 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).
Trial Locations
- Locations (32)
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes, France
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
MHAT for women's health - Nadezhda, OOD
🇧🇬Sofia, Bulgaria
CHU Angers - Hôpital Larrey
🇫🇷Angers, France
Hôpital Ambroise Paré
🇫🇷Boulogne Billancourt, France
Hôpital Privé du Confluent
🇫🇷Nantes, France
NHO Kyushu Cancer Center
🇯🇵Fukuoka-shi, Japan
Antoni van Leeuwenhoek
🇳🇱Amsterdam, Netherlands
Guy's Hospital
🇬🇧London, United Kingdom
Oncology Hematology West
🇺🇸Omaha, Nebraska, United States
Clinical Research Alliance
🇺🇸Westbury, New York, United States
NHO Hokkaido Cancer Center
🇯🇵Hokkaido, Japan
Cancer Institute Hospital of JFCR
🇯🇵Koto City, Japan
NHO Nagoya Medical Center
🇯🇵Nagoya, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Osaka Medical and Pharmaceutical University Hospital
🇯🇵Osaka, Japan
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Pan American Oncology Trials, LLC
🇵🇷San Juan, Puerto Rico
National Cancer Center Korea
🇰🇷Goyang-si, Korea, Republic of
Auxilio Mutuo Cancer Center
🇵🇷San Juan, Puerto Rico
Barts Hospital
🇬🇧London, United Kingdom
Ocala Oncology Center P.L.
🇺🇸Ocala, Florida, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
University of Tennessee Medical Center Cancer Institute
🇺🇸Knoxville, Tennessee, United States
Nippon Medical School Hospital
🇯🇵Bunkyo-ku, Japan
Miyagi Cancer Center
🇯🇵Natori-shi, Japan
Ajou University Hospital
🇰🇷Suwon, Gyeonggi-do, Korea, Republic of
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of