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

Advanced Endometrial Cancer Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT06046274
• Other study ID #: GCT1046-05
• Secondary ID: 2022-502453-33-0
• Status: Withdrawn
• Phase: Phase 2
• Start date: October 1, 2023
• Est. completion date: June 1, 2028

Study information

• Verified date: April 2024
• Source: Genmab
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 1, 2028
• Est. primary completion date: April 1, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Mullerian 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.

Related Conditions & MeSH terms

• Advanced Endometrial Cancer
• Endometrial Neoplasms

Intervention

Biological:
• Pembrolizumab
Pembrolizumab intravenous (IV) infusion
• Acasunlimab
Acasunlimab IV infusion

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussel
Belgium	Grand Hospital de Charleroi	Charleroi
Belgium	Universitair Ziekenhuis Ghent	Ghent
Belgium	UZ Leuven	Leuven
Denmark	Aalborg University Hospital	Aalborg
Denmark	Rigshospitalet	Copenhagen
Denmark	Odense Universitetshospital	Odense
Italy	AOU Policlinico Sant'Orsola Malpighi IRCCS	Bologna
Italy	IRCCS Istituto Europeo di Oncologia IEO	Milano
Italy	Fondazione G. Pascale	Napoli
Italy	IRCCS Policlinico Universitario Agostino Gemelli	Roma
Italy	Ospedale Mauriziano Umberto I	Torino
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	National Cancer Center Korea	Goyang-si
Korea, Republic of	Pusan National University	Pusan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System|Division of Infectious Diseases	Seoul
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	ICO Girona	Girona
Spain	Clínica Universidad de Navarra	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jiménez Díaz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Clínica Universidad de Navarra	Pamplona
United States	Rudgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Orlando Health Cancer Institute	Orlando	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	BioNTech SE

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  Italy,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Duration of Response (DOR)	DOR is defined for responders as the time from initial onset of response to first progression event, defined as radiographic progression or death as per RECIST v1.1.	Up to 4 years
Secondary	Time to Response (TTR)	TTR is defined as the time from first infusion of trial treatment to onset of response as per RECIST v1.1.	Up to 4 years
Secondary	Disease Control Rate (DCR)	DCR is defined as the proportion of participants with a confirmed response of PR or CR or stable disease (SD) according to RECIST v1.1.	Up to 4 years
Secondary	Number of Participants with Treatment Emergent Adverse Events (TEAEs) and as Per Severity	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product as per CTCAE V5.0. TEAE is defined as an AE occurring or worsening between the first dose of study drug and 30 days after the last dose received.	From first dose date up to 90 days after the study treatment