MK-2870 in Post Platinum and Post Immunotherapy Endometrial Cancer (MK-2870-005)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06132958

Collaborator

(none)

710

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The primary objectives of this study are to compare MK-2870 to Treatment of Physician's Choice (TPC) with respect to progression-free survival (PFS) per RECIST 1.1, as assessed by blinded independent central review (BICR), and overall survival (OS). The primary hypotheses are that MK-2870 is superior to TPC with respect to PFS per RECIST 1.1, as assessed by BICR, and that MK-2870 is superior to TPC with respect to OS.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Cancer	Biological: MK-2870 Drug: Doxorubicin Drug: Paclitaxel	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

710 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Randomized, Active-controlled, Open-label, Multicenter Study to Compare the Efficacy and Safety of MK-2870 Monotherapy Versus Treatment of Physician's Choice in Participants With Endometrial Cancer Who Have Received Prior Platinum-based Chemotherapy and Immunotherapy (MK-2870-005/ENGOT-en23/GOG-3095)

Anticipated Study Start Date :

Dec 12, 2023

Anticipated Primary Completion Date :

Jan 10, 2028

Anticipated Study Completion Date :

Jan 10, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MK-2870 Participants will receive 4 mg/kg of MK-2870 via intravenous (IV) infusion on Day 1 of each 14-day cycle. Additionally, participants receive diphenhydramine (or equivalent), an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of MK-2870. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.	Biological: MK-2870 4 mg/kg of MK-2870 by IV infusion Other Names: SKB264
Active Comparator: Chemotherapy Participants will receive 60 mg/m^2 of doxorubicin by IV infusion on Day 1 of each 21-day cycle; or 80 mg/m^2 of paclitaxel by IV infusion on Days 1, 8, and 15 of each 28-day cycle.	Drug: Doxorubicin 60 mg/m^2 of doxorubicin by IV Infusion Other Names: ADRIAMYCIN® Drug: Paclitaxel 80 mg/m^2 of paclitaxel by IV infusion Other Names: TAXOL®

Arm

Intervention/Treatment

Experimental: MK-2870

Participants will receive 4 mg/kg of MK-2870 via intravenous (IV) infusion on Day 1 of each 14-day cycle. Additionally, participants receive diphenhydramine (or equivalent), an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of MK-2870. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.

Biological: MK-2870

4 mg/kg of MK-2870 by IV infusion

Other Names:

SKB264

Active Comparator: Chemotherapy

Participants will receive 60 mg/m^2 of doxorubicin by IV infusion on Day 1 of each 21-day cycle; or 80 mg/m^2 of paclitaxel by IV infusion on Days 1, 8, and 15 of each 28-day cycle.

Drug: Doxorubicin

60 mg/m^2 of doxorubicin by IV Infusion

Other Names:

ADRIAMYCIN®

Drug: Paclitaxel

80 mg/m^2 of paclitaxel by IV infusion

Other Names:

TAXOL®

Outcome Measures

Primary Outcome Measures

Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR) [Up to approximately 4 years]
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first.
Overall Survival (OS) [Up to approximately 4 years]
OS is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR [Up to approximately 4 years]
ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. based on BICR
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR [Up to approximately 4 years]
For participants who demonstrate confirmed CR or PR per RECIST 1.1 as assessed by BICR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first
Number of Participants Who Experience One or More Adverse Events (AEs) [Up to approximately 4 years]
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention whether or not considered related to the study intervention.
Number of Participants Who Discontinue Study Intervention Due to an AE [Up to approximately 4 years]
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention whether or not considered related to the study intervention.
Change from Baseline in Global Health Status/Quality of Life Score (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 [EORTC QLQ-C30]) [Up to approximately 4 years]
The EORTC QLQ-C30 is a questionnaire to assess the overall health status and quality of life of cancer patients. Participant responses to the questions, "How would you rate your overall health during the past week (Item 29)?" and "How would you rate your overall quality of life during the past week (Item 30)?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status and quality of life. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

Has a histologically-confirmed diagnosis of endometrial carcinoma or carcinosarcoma.
Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST 1.1, as assessed by BICR.
Has received prior platinum-based chemotherapy and anti-programmed cell death 1 protein (PD-1)/anti- programmed cell death ligand 1 (PD-L1) therapy, either separately or in combination.

Exclusion Criteria:

Has neuroendocrine tumors or endometrial sarcoma, including stromal sarcoma, leiomyosarcoma, adenosarcoma, or other types of pure sarcomas.
Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease.
Has had a recurrence of endometrial carcinoma or carcinosarcoma more than 180 days after completing platinum-based therapy administered in the curative-intent or adjuvant setting without any additional platinum-based therapy received in the metastatic or recurrent setting.
Has received more than 3 prior lines of therapy for endometrial carcinoma or carcinosarcoma.