Phase 3 study of pembrolizumab vs chemotherapy in dMMR advanced or recurrent endometrial carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Apr 2022 → ongoing

Decision date (initial)

2023-12-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506361-56-00

EudraCT number

2021-003185-12

WHO UTN

U1111-1292-6057

ClinicalTrials.gov

NCT05173987

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Therapy, Safety, Pharmacogenomic, Efficacy

1. To compare pembrolizumab to chemotherapy with respect to PFS per RECIST 1.1 as assessed by BICR
2. To compare pembrolizumab to chemotherapy with respect to OS

Secondary objectives 7

1. To compare pembrolizumab to chemotherapy with respect to ORR per RECIST 1.1 by BICR in participants with measurable disease at study entry
2. To compare pembrolizumab to chemotherapy with respect to DCR per RECIST 1.1 by BICR in participants with measurable disease at study entry
3. To compare pembrolizumab to chemotherapy with respect to DOR per RECIST 1.1 by BICR in participants with measurable disease at study entry
4. To compare pembrolizumab to chemotherapy with respect to PFS per RECIST 1.1 as assessed by the investigator
5. To compare pembrolizumab to chemotherapy with respect to PFS2 per RECIST 1.1 as assessed by the investigator
6. To compare the safety and tolerability of pembrolizumab to chemotherapy
7. To compare pembrolizumab to chemotherapy with respect to change from baseline score in the EORTC QLQ-C30 GHS/QoL

Conditions and MedDRA coding

Endometrial cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Has a histologically confirmed diagnosis of inoperable, Stage III or IV or recurrent Endometrial Carcinoma (EC) or carcinosarcoma (mixed Mullerian tumor) that is centrally confirmed as dMMR.
2. Has radiographically evaluable disease, either measurable or non-measurable per RECIST 1.1, as assessed by the investigator. Note: primary Stage IVB that has undergone surgical resection is allowed regardless of presence of measurable or evaluable disease.
3. Has received no prior systemic therapy for EC except for the following: a. May have received 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy in the setting of curative-intent resection if the recurrence occurred ≥6 months after the last dose of chemotherapy. b. May have received prior radiation with or without radiosensitizing chemotherapy if >2 weeks before the start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease. c. c. May have received prior hormonal therapy for treatment of EC, provided that it was discontinued ≥1 week prior to randomization.
4. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization.
5. Is not pregnant or breastfeeding and agrees to not donate eggs and use a highly effective contraceptive method for 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapy if a woman of childbearing potential (WOCBP)
6. Has a negative highly sensitive pregnancy test (urine or serum) within 24 hours for urine or 72 hours for serum before the first dose of study intervention if a WOCBP
7. Provides an archival tumor tissue sample or newly obtained (core, incisional, or excisional) biopsy of a tumor lesion not previously irradiated for verification of dMMR status and histology
8. Is Hepatitis B surface antigen (HBsAg) positive but has received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load prior to randomization
9. Has a history of Hepatitis C virus (HCV) infection but has undetectable HCV viral load at screening.

Exclusion criteria 17

1. Has uterine mesenchymal tumor such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas. Adenosarcomas and neuroendocrine tumors are not allowed.
2. Has EC of any histology that is proficient mismatch repair (pMMR).
3. Is a candidate for curative-intent surgery or curative-intent radiotherapy
4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137]).
5. Has received prior systemic anticancer therapy including investigational agents for any advanced or metastatic EC. (Note: Prior chemotherapy administered as adjuvant therapy, neoadjuvant therapy, and/or concurrently with radiation is permitted.
6. Has had a major operation and has not recovered adequately from the procedure and/or any complications from the operation before starting study intervention.
7. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
8. Is currently participating in or has participated in a study of an investigational agent for EC, has participated in a study of an investigational agent for non-EC within 4 weeks before the first dose of study intervention, or has used an investigational device within 4 weeks before the first dose of study intervention
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
10. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (excluding carcinoma in situ of the bladder) that have undergone potentially curative therapy are not excluded
11. Has known active CNS metastases and/or carcinomatous meningitis
12. Has a known intolerance to any study intervention and/or any of its excipients
13. Has an active autoimmune disease that has required systemic treatment in past 2 years
14. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
15. Has an active infection, requiring systemic therapy
16. Has a known history of human immunodeficiency virus (HIV) infection
17. Has had an allogenic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
2. Overall survival (OS)

Secondary endpoints 8

1. Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR
2. Disease Control Rate (DCR) per RECIST 1.1 as Assessed by BICR
3. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
4. PFS per RECIST 1.1 as Assessed by Investigator
5. Progression-Free Survival 2 (PFS2) per RECIST 1.1 as Assessed by Investigator
6. Number of Participants Who Experience at Least One Adverse Event (AE)
7. Number of Participants Who Discontinue Study Treatment Due to an AE
8. Change From Baseline in European Organization for Research And Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS) (Item 29) And Quality of Life (QoL) (Item 30) Combined Score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Vivek Khemka

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Vivek Khemka

Third parties 8

Locations

13 EU/EEA countries · 56 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 146 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications