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

Genmab

Status and phase: Enrolling; Phase 3

Conditions: PD-L1-positive Metastatic NSCLC

Treatments: Drug: Pembrolizumab; Drug: Docetaxel; Drug: Acasunlimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06635824

jRCT2051240178 (Registry Identifier)

2024-512998-27-00 (EU Trial (CTIS) Number)

GCT1046-06

Details and patient eligibility

About

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.

Full 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.

Enrollment: 702 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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702 participants in 2 patient groups

Arm A

Experimental group

Description:

Acasunlimab, 100 mg and pembrolizumab, 400 mg will be administered via intravenous (IV) infusion, once every 6 weeks (Q6W) (Cycle length=42 days).

Treatment:

Drug: Acasunlimab

Drug: Pembrolizumab

Arm B

Active Comparator group

Description:

Docetaxel, 75 mg/m\^2 will be administered via IV infusion, once every 3 weeks (Q3W) (Cycle length=21 days).

Treatment:

Drug: Docetaxel