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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06046274
Recruitment Status : Withdrawn (Enrollment challenged by availability of other treatment options)
First Posted : September 21, 2023
Last Update Posted : April 30, 2024
Sponsor:
Collaborator:
BioNTech SE
Information provided by (Responsible Party):
Genmab

Tracking Information
First Submitted Date  ICMJE September 14, 2023
First Posted Date  ICMJE September 21, 2023
Last Update Posted Date April 30, 2024
Estimated Study Start Date  ICMJE October 1, 2023
Estimated Primary Completion Date April 1, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2023)
Objective Response Rate (ORR) [ Time Frame: Up to 4 years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2023)
  • Duration of Response (DOR) [ Time Frame: Up to 4 years ]
    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.
  • Time to Response (TTR) [ Time Frame: Up to 4 years ]
    TTR is defined as the time from first infusion of trial treatment to onset of response as per RECIST v1.1.
  • Disease Control Rate (DCR) [ Time Frame: Up to 4 years ]
    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.
  • Number of Participants with Treatment Emergent Adverse Events (TEAEs) and as Per Severity [ Time Frame: From first dose date up to 90 days after the study treatment ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE GEN1046 in Combination With Anticancer Agents for the Treatment of Advanced Endometrial Cancer
Official Title  ICMJE 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
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Endometrial Cancer
Intervention  ICMJE
  • Biological: Pembrolizumab
    Pembrolizumab intravenous (IV) infusion
  • Biological: Acasunlimab
    Acasunlimab IV infusion
    Other Names:
    • GEN1046
    • DuoBody®-PD-L1x4-1BB
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Biological: Pembrolizumab
    • Biological: Acasunlimab
  • Experimental: 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.
    Interventions:
    • Biological: Pembrolizumab
    • Biological: Acasunlimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: April 29, 2024)
0
Original Estimated Enrollment  ICMJE
 (submitted: September 14, 2023)
80
Estimated Study Completion Date  ICMJE June 1, 2028
Estimated Primary Completion Date April 1, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Denmark,   Italy,   Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT06046274
Other Study ID Numbers  ICMJE GCT1046-05
2022-502453-33-00 ( EU Trial (CTIS) Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Genmab
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Genmab
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE BioNTech SE
Investigators  ICMJE
Study Director: Study Official Genmab
PRS Account Genmab
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP