Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06)

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 prot...

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 usi...

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
702
Inclusion Criteria
  • Participant has histologically or cytologically confirmed metastatic NSCLC (stage IV).

  • 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.

  • 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

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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), 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.

  • 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.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm AAcasunlimabAcasunlimab, 100 mg and pembrolizumab, 400 mg will be administered via intravenous (IV) infusion, once every 6 weeks (Q6W) (Cycle length=42 days).
Arm APembrolizumabAcasunlimab, 100 mg and pembrolizumab, 400 mg will be administered via intravenous (IV) infusion, once every 6 weeks (Q6W) (Cycle length=42 days).
Arm BDocetaxelDocetaxel, 75 mg/m\^2 will be administered via IV infusion, once every 3 weeks (Q3W) (Cycle length=21 days).
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
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 AcasunlimabPredose 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 AcasunlimabUp 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) ScoreUp 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 bother...

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 ...

Trial Locations

Locations (5)

Ocala Oncology Center P.L.

🇺🇸

Ocala, Florida, United States

Clinical Research Alliance

🇺🇸

Westbury, New York, United States

Miyagi Cancer Center

🇯🇵

Natori-shi, Japan

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Oncology Hematology West

🇺🇸

Omaha, Nebraska, United States

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