Study of the Effectiveness and Safety of Acasunlimab Alone and With Pembrolizumab to Treat Advanced Melanoma of the Skin That Has Returned After Treatment With an Approved Checkpoint Inhibitor Therapy (ABBIL1TY MELANOMA-07)

Phase 2

Not yet recruiting

• Conditions: Cutaneous Melanoma; Relapsed/Refractory, Locally Advanced Unresectable Melanoma (Stage IIIB, IIIC, or IIID); Metastatic Cutaneous Melanoma (Stage IV)
• Interventions: Biological: Acasunlimab; Biological: Pembrolizumab

• Registration Number: NCT06984328
• Lead Sponsor: Genmab

Brief Summary

The goal of this clinical trial is to learn about the effectiveness and safety of the bispecific antibody acasunlimab (also known as DuoBody®-PD-L1x4-1BB) when given either alone or together with the cancer drug pembrolizumab in participants with locally advanced or metastatic melanoma of the skin. All participants will receive active drugs; no one will be given a placebo.

The trial duration will be approximately 15 months for each participant, including a 28-day screening period and estimated 4-month treatment and 10-month follow-up periods; however, the duration of the treatment and follow-up periods may vary for each participant.

Participants will have regular check-ups while on treatment, with visits every week initially, and then every 3 weeks later in the trial.

Detailed Description

This is a Phase 2, randomized, open-label, multicenter trial evaluating the efficacy and safety of acasunlimab as monotherapy and in combination with pembrolizumab in adult participants with relapsed/refractory, unresectable locally advanced or metastatic cutaneous melanoma who progressed on or after prior checkpoint inhibitor (CPI)-containing therapy. Participants will be randomized in a 1:1 ratio to receive acasunlimab and pembrolizumab or acasunlimab alone.

Eligible participants must have received a minimum of 2 cycles of an approved anti-programmed cell death protein 1 (PD-1) containing therapy. Participants whose tumor harbors a B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600 mutation are eligible for the trial if they have received a BRAF-directed therapy (with or without a mitogen-activated protein kinase \[MEK\] inhibitor) prior to enrollment in the trial, unless the investigator has deemed a BRAF-directed therapy not clinically indicated. BRAF V600 mutational status must be determined by local assessment and documented.

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-14
• Study First Submitted QC: 2025-05-14
• Last Update Submitted: 2025-05-14
• Study First Posted: 2025-05-22
• Last Update Posted: 2025-05-22
• Study Start: 2025-06-30
• Primary Completion: 2027-07-15
• Study Completion: 2029-07-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• Participants ≥ 18 years of age with histologically or cytologically confirmed diagnosis of relapsed/refractory, locally advanced unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, per American Joint Committee on Cancer (8th edition) staging.
• Participant must have radiographic progression based on RECIST v1.1 on or following ≥ 1 prior systemic therapy, according to local and international guidelines, including a programmed cell death protein 1 blocking antibody (anti-PD-1) treatment or combination treatment containing an anti-PD-1.
• Participant must have received a minimum of 2 cycles of an approved anti-PD-1 as monotherapy or a combination therapy containing an anti-PD-1.
• Neoadjuvant and/or adjuvant systemic therapy count as the first line of prior systemic therapy if there is documented disease progression ≤ 6 months after completion of therapy.
• Participants with a BRAF V600 mutation should have received prior BRAF-directed therapy (with or without a MEK inhibitor) prior to enrollment in the trial, unless deemed not clinically indicated by the Investigator due to concurrent medical condition or prior toxicity.
• Participant has an Eastern Cooperative Oncology Group performance status of 0 or 1 within 7 days prior to Cycle 1 Day 1.

Key

Exclusion Criteria

• Participants with non-cutaneous or acral melanoma.
• Participants with newly identified or known unstable or symptomatic central nervous system metastases or history of carcinomatous meningitis.

Note: Other protocol-defined Inclusion and Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acasunlimab in Combination with Pembrolizumab	Acasunlimab	Participants with relapsed/refractory, unresectable locally advanced or metastatic cutaneous melanoma that progressed on/after prior CPI(s) will receive acasunlimab once every 6 weeks (Q6W) in combination with pembrolizumab Q6W.
Acasunlimab in Combination with Pembrolizumab	Pembrolizumab	Participants with relapsed/refractory, unresectable locally advanced or metastatic cutaneous melanoma that progressed on/after prior CPI(s) will receive acasunlimab once every 6 weeks (Q6W) in combination with pembrolizumab Q6W.
Acasunlimab	Acasunlimab	Participants with relapsed/refractory, unresectable locally advanced or metastatic cutaneous melanoma that progressed on/after prior CPI(s) will receive acasunlimab Q6W.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to approximately 12 months	Assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Up to approximately 15 months
Time to Treatment Discontinuation Due to Adverse Events (AEs)	Up to approximately 15 months
Time to Response (TTR)	Up to approximately 15 months	Assessed by the investigator per RECIST v1.1.
Duration of Response (DOR)	Up to approximately 15 months	Assessed by the investigator per RECIST v1.1.
Progression-free Survival (PFS)	Up to approximately 15 months	Assessed by the investigator per RECIST v1.1.
Overall Survival (OS)	Up to approximately 15 months