GEN1046 in Combination With Anticancer Agents for the Treatment of Advanced Endometrial Cancer

NCT06046274 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: GCT1046-052022-502453-33-00
• Study Type: interventional
• Target: N/A
• Locations: 6 countries
• Sites: 29

Brief Summary

The goal of this clinical study is to learn about the bispecific antibody, acasunlimab (also known as GEN1046) in combination with the cancer drug pembrolizumab for treatment of participants with incurable endometrial cancer (cancer of the womb). The main questions the study aims to answer are:

• How well acasunlimab in combination with pembrolizumab works against endometrial cancer
• What are the potential side effects participants may experience when they are treated with acasunlimab in combination with pembrolizumab Participants will receive both acasunlimab and pembrolizumab. All participants will receive active drug; no one will receive placebo. participants will participate in 1 of 2 cohorts. A participant will receive study treatment up to a maximum of 24 months. The study duration (including screening, treatment, and follow-up) for each participant will be about 39 months.

Conditions

Advanced Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of participants with a confirmed response of partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.

  Up to 4 years

Secondary Outcomes (4)

• Duration of Response (DOR)

  Up to 4 years

• Time to Response (TTR)

  Up to 4 years

• Disease Control Rate (DCR)

  Up to 4 years

• Number of Participants with Treatment Emergent Adverse Events (TEAEs) and as Per Severity

  From first dose date up to 90 days after the study treatment

Study Arms (2)

Cohort A: pembrolizumab + acasunlimab

EXPERIMENTAL

Pembrolizumab will be administered in combination with acasunlimab as second-line (2L) or third-line (3L) therapy for dMMR/MSI-H in checkpoint inhibitor (CPI) naïve participants.

Biological: Pembrolizumab; Biological: Acasunlimab

Cohort B: pembrolizumab + acasunlimab

EXPERIMENTAL

Pembrolizumab will be administered in combination with acasunlimab as 2L or 3L therapy for mismatch repair deficient/ microsatellite instability-high (dMMR/MSI-H) participants who had prior exposure to programmed cell death protein/ programmed death ligand 1 (PD-1/PD-L1) inhibitors.

Biological: Pembrolizumab; Biological: Acasunlimab

Interventions

Pembrolizumab BIOLOGICAL

Pembrolizumab intravenous (IV) infusion

Cohort A: pembrolizumab + acasunlimab; Cohort B: pembrolizumab + acasunlimab

Acasunlimab BIOLOGICAL

Acasunlimab IV infusion

Also known as: GEN1046, DuoBody®-PD-L1x4-1BB

Cohort A: pembrolizumab + acasunlimab; Cohort B: pembrolizumab + acasunlimab

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a histologically confirmed diagnosis of advanced (unresectable, recurrent, and/or metastatic) endometrial carcinoma that is incurable and for which prior standard first-line treatment has failed.
• Prior to Cycle 1 Day 1 (C1D1), documentation of tumor dMMR/MSI-H status must be available based on local testing.
• Must have progressed on or after at least 1 (but no more than 2) prior line(s) of a systemic chemotherapy regimen for unresectable and/or metastatic endometrial cancer of which at least 1 regimen of platinum-based treatment unless participant is ineligible for or intolerant to platinum.
• Cohort A only: Must be treatment naive for CPIs including PD-1 or PD-L1 inhibitors and other immune CPIs (eg, anti-CTLA-4, anti-LAG3, anti-TIGIT).
• Cohort B only: Must have received and progressed on or after prior treatment with a PD-1/PD-L1 inhibitor alone or in combination. Moreover, the participant's duration of CPI containing treatment and best overall response (BOR) is known, and participant has received a minimum of 2 cycles of CPI.

You may not qualify if:

• Histological diagnosis of carcinosarcoma, malignant mixed Műllerian tumor, endometrial leiomyosarcoma, or endometrial stromal sarcomas.
• Ongoing or active infection requiring intravenous treatment with anti-infective therapy, or any ongoing systemic inflammatory condition requiring further diagnostic work-up or management during screening.
• Any prior treatment with any type of antitumor vaccine, or autologous cell immunotherapy.
• Radiotherapy within 14 days prior to first dose of acasunlimab. Note: palliative radiotherapy will be allowed for local pain control under certain conditions.
• Treatment with an anticancer agent, including investigational vaccines within 28 days before or 5 times t1/2, whichever is shorter, prior to the planned first dose of trial treatment or is currently enrolled in an interventional trial.
• Prior treatment with live, attenuated vaccines within 30 days prior to initiation of trial treatment.
• Received granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support within 4 weeks before the planned first dose of trial treatment.
• Cohort A only: Prior exposure to immune CPIs other than anti-PD-1/anti-PD-L1 (eg, anti-CTLA-4, anti-LAG3, anti-TIGIT) or agents directed at costimulatory T-cell receptors (eg, 4-1BB, OX40)
• Cohort B only:
• Known history of Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy treatment
• Exposure to any of the following prior therapies/treatments within the specified timeframes:
• Prior exposure to immune CPIs other than anti-PD-1/anti-PD-L1 (eg, anti-CTLA-4, anti-LAG3, anti-TIGIT) or agents directed at costimulatory T-cell receptors (eg, 4-1BB, OX40)
• PD-1/PD-L1 antibody within 28 days before the planned first dose of trial treatment

Sponsors & Collaborators

• Genmab: lead
• BioNTech SE: collaborator

Study Sites (29)

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

Location

Rudgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Grand Hospital de Charleroi

Charleroi, Belgium

Location

Universitair Ziekenhuis Ghent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Aalborg University Hospital

Aalborg, 9100, Denmark

Location

Rigshospitalet

Copenhagen, Denmark

Location

Odense Universitetshospital

Odense, Denmark

Location

AOU Policlinico Sant'Orsola Malpighi IRCCS

Bologna, Italy

Location

IRCCS Istituto Europeo di Oncologia IEO

Milan, Italy

Location

Fondazione G. Pascale

Napoli, Italy

Location

IRCCS Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

Ospedale Mauriziano Umberto I

Torino, Italy

Location

Keimyung University Dongsan Medical Center

Daegu, South Korea

Location

National Cancer Center Korea

Goyang-si, South Korea

Location

Pusan National University

Pusan, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System|Division of Infectious Diseases

Seoul, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

ICO Girona

Girona, Spain

Location

Clínica Universidad de Navarra

Madrid, 28027, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Fundacion Jiménez Díaz

Madrid, Spain

Location

Clínica Universidad de Navarra

Pamplona, 31008, Spain

Location

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Study Official

  Genmab

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2023
• First Posted: September 21, 2023
• Study Start: October 1, 2023
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 30, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (7); BE (4); DK (3); US (2); IT (5); KR (8)