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

NCT ID: NCT06046274

Last Updated: 2024-04-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-01
• Study Completion Date: 2028-06-01

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.

Detailed Description

This is an open-label multicenter study in participants with advanced (unresectable and/or metastatic) endometrial cancer to evaluate the safety and clinical activity of acasunlimab (GEN1046) in combination with immunotherapy.

The trial consists of two cohorts:

• Cohort A (cohort closed)
• Cohort B

The study will enroll approximately 80 participants in Cohort A and B (approximately 40 participants in each cohort).

Conditions

Advanced Endometrial Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: pembrolizumab + acasunlimab

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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

Pembrolizumab intravenous (IV) infusion

Acasunlimab

Intervention Type: BIOLOGICAL

Acasunlimab IV infusion

Cohort B: pembrolizumab + acasunlimab

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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

Pembrolizumab intravenous (IV) infusion

Acasunlimab

Intervention Type: BIOLOGICAL

Acasunlimab IV infusion

Interventions

Pembrolizumab

Pembrolizumab intravenous (IV) infusion

Intervention Type: BIOLOGICAL

Acasunlimab

Acasunlimab IV infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

GEN1046; DuoBody®-PD-L1x4-1BB

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

BioNTech SE

INDUSTRY

Sponsor Role: collaborator

Genmab

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Official

Role: STUDY_DIRECTOR

Genmab

Locations

Orlando Health Cancer Institute

Orlando, Florida, United States

Rudgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Grand Hospital de Charleroi

Charleroi, , Belgium

Universitair Ziekenhuis Ghent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

Aalborg University Hospital

Aalborg, , Denmark

Rigshospitalet

Copenhagen, , Denmark

Odense Universitetshospital

Odense, , Denmark

AOU Policlinico Sant'Orsola Malpighi IRCCS

Bologna, , Italy

IRCCS Istituto Europeo di Oncologia IEO

Milan, , Italy

Fondazione G. Pascale

Napoli, , Italy

IRCCS Policlinico Universitario Agostino Gemelli

Roma, , Italy

Ospedale Mauriziano Umberto I

Torino, , Italy

Keimyung University Dongsan Medical Center

Daegu, , South Korea

National Cancer Center Korea

Goyang-si, , South Korea

Pusan National University

Pusan, , South Korea

Seoul National University Bundang Hospital

Seongnam, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

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

Seoul, , South Korea

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

ICO Girona

Girona, , Spain

Clínica Universidad de Navarra

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Fundacion Jiménez Díaz

Madrid, , Spain

Clínica Universidad de Navarra

Pamplona, , Spain

Countries

United States; Belgium; Denmark; Italy; South Korea; Spain

Other Identifiers

2022-502453-33-00

Identifier Type: CTIS

Identifier Source: secondary_id

GCT1046-05

Identifier Type: -

Identifier Source: org_study_id