Clinical trial NCT06046274: GEN1046 in Combination With Anticancer Agents for the Treatment of Advanced Endometrial Cancer
Official title: A Phase 2 Exploratory, Multicenter, Open-Label Trial to Determine the Safety and Preliminary Clinical Activity of GEN1046 in Combination With Anticancer Agents in Subjects With Advanced Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Advanced Endometrial Cancer
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: BioNTech SE
First posted: 2023-09-21
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to 4 years
measure: Time to Response (TTR)
timeFrame: Up to 4 years
measure: Disease Control Rate (DCR)
timeFrame: Up to 4 years
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and as Per Severity
timeFrame: From first dose date up to 90 days after the study treatment
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: New Brunswick
country: United States
facility: Rudgers Cancer Institute of New Jersey
state: New Jersey
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hospital de Charleroi
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Ghent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Bologna
country: Italy
facility: AOU Policlinico Sant'Orsola Malpighi IRCCS
city: Milano
country: Italy
facility: IRCCS Istituto Europeo di Oncologia IEO
city: Napoli
country: Italy
facility: Fondazione G. Pascale
city: Roma
country: Italy
facility: IRCCS Policlinico Universitario Agostino Gemelli
city: Torino
country: Italy
facility: Ospedale Mauriziano Umberto I
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center Korea
city: Pusan
country: Korea, Republic of
facility: Pusan National University
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System|Division of Infectious Diseases
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Girona
country: Spain
facility: ICO Girona
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jiménez Díaz
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: