Advanced Endometrial CancerPhase 2NCT06046274
GEN1046 in Combination With Anticancer Agents for the Treatment of Advanced Endometrial Cancer
A Phase 2 study testing Pembrolizumab and Acasunlimab in people with Advanced Endometrial Cancer, run by Genmab at 29 sites in 6 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Advanced Endometrial Cancer
- What is being tested?
- Pembrolizumab and Acasunlimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 29 sitesin 6 countries
- Study dates
- 1 Oct 2023to 1 Jun 2028
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
29 sites in 6 countries.
29 sites in 6 countries
South Korea8 sites
Keimyung University Dongsan Medical Center
Daegu
National Cancer Center Korea
Goyang-si
Pusan National University
Pusan
Seoul National University Bundang Hospital
Seongnam
Asan Medical Center
Seoul
Samsung Medical Center
Seoul
Seoul National University Hospital
Seoul
Severance Hospital, Yonsei University Health System|Division of Infectious Diseases
Seoul
Spain7 sites
Hospital Universitari Vall d'Hebron
Barcelona
ICO Girona
Girona
Clínica Universidad de Navarra
Madrid, 28027
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Fundacion Jiménez Díaz
Madrid
Clínica Universidad de Navarra
Pamplona, 31008
Italy5 sites
AOU Policlinico Sant'Orsola Malpighi IRCCS
Bologna
IRCCS Istituto Europeo di Oncologia IEO
Milan
Fondazione G. Pascale
Naples
IRCCS Policlinico Universitario Agostino Gemelli
Roma
Ospedale Mauriziano Umberto I
Torino
Belgium4 sites
Cliniques Universitaires Saint-Luc
Brussels, 1200
Grand Hospital de Charleroi
Charleroi
Universitair Ziekenhuis Ghent
Ghent, 9000
UZ Leuven
Leuven, 3000
Denmark3 sites
Aalborg University Hospital
Aalborg, 9100
Rigshospitalet
Copenhagen
Odense Universitetshospital
Odense
United States2 sites
Rudgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Orlando Health Cancer Institute
Orlando, Florida, 32806
About this study
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
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.
Read the 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
- Being tested
- Pembrolizumab, Acasunlimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Pembrolizumab intravenous (IV) infusion
AcasunlimabBiological
Also called GEN1046, DuoBody®-PD-L1x4-1BB
Acasunlimab IV infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Pembrolizumab; Biological: Acasunlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 4 years
Secondary outcomes (4)
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.
Measured: Up to 4 years
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.
Measured: Up to 4 years
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.
Measured: Up to 4 years
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.
Measured: From first dose date up to 90 days after the study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start1 Oct 2023 (estimated)
- Primary completion1 Apr 2028 (estimated)
- Study completion1 Jun 2028 (estimated)
Why it stopped: Enrollment challenged by availability of other treatment options
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Endometrial CancerStudies of the same condition, open and under way.
- More trials run by GenmabThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genmab
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- BioNTech SE
- Responsible party
- Sponsor
- Investigators
- Study Official, Study director, Genmab
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06046274
- Sponsor's protocol ID
- GCT1046-05
- Other IDs
- 2022-502453-33-00
- Status last verified
- Apr 2024
- First submitted
- 14 Sep 2023
- Last updated
- 30 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06046274
- Acronym / sponsor ID
- GCT1046-05
- Conditions
- Advanced Endometrial Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Enrollment challenged by availability of other treatment options
- Enrolment
- 0 participants (actual)
- Lead sponsor
- GenmabIndustry (pharma, biotech, devices)
- Collaborators
- BioNTech SE
- Study start
- 1 Oct 2023 (estimated)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 21 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: pembrolizumab + acasunlimab | Experimental | Biological: Pembrolizumab, Biological: AcasunlimabPembrolizumab 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. |
| Cohort B: pembrolizumab + acasunlimab | Experimental | Biological: Pembrolizumab, Biological: AcasunlimabPembrolizumab 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabPembrolizumab intravenous (IV) infusion | Biological | Cohort A: pembrolizumab + acasunlimab, Cohort B: pembrolizumab + acasunlimab |
| AcasunlimabAlso: GEN1046, DuoBody®-PD-L1x4-1BBAcasunlimab IV infusion | Biological | Cohort A: pembrolizumab + acasunlimab, Cohort B: pembrolizumab + acasunlimab |
Primary outcome
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.
4 secondary outcomes
Duration of Response (DOR)
Time frame: Up to 4 years
Time to Response (TTR)
Time frame: Up to 4 years
Disease Control Rate (DCR)
Time frame: Up to 4 years
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Official study director
Genmab
29 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Acasunlimab in people with Advanced Endometrial Cancer, run by Genmab at 29 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 30 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in South Korea, Spain, Italy, Belgium, Denmark and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Up to 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2024.