A Randomized, Phase 2 Study of Pembrolizumab And Chemotherapy With or Without MK-4830 as Neoadjuvant Treatment for High-Grade Serous Ovarian Cancer

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

27 Jul 2022 → 15 Oct 2024

Decision date (initial)

2024-02-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-505005-16-00

EudraCT number

2021-005458-27

WHO UTN

U1111-1290-6634

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacoeconomic, Therapy, Pharmacogenomic, Efficacy, Pharmacodynamic

Among patients with detectable ctDNA at baseline, to evaluate whether the reduction from baseline in circulating tumor DNA at Cycle 3 (ΔctDNA) is larger in participants receiving MK-4830 + pembrolizumab in combination with standard of care (SOC) therapy than in those receiving pembrolizumab + SOC therapy.

Secondary objectives 3

1. Among patients with detectable ctDNA at baseline, to evaluate the association between neoadjuvant ΔctDNA at Cycle 3 from baseline and surgical outcomes.
2. To estimate the difference in pCR and CRS following neoadjuvant treatment between arms.
3. To evaluate the safety and tolerability of the study intervention administered.

Conditions and MedDRA coding

Primary peritoneal cancer/Fallopian tube cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Has histologically-confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV HGSOC, primary peritoneal cancer, or fallopian tube cancer.
2. Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the neoadjuvant and adjuvant setting.
3. Is a candidate for interval debulking surgery.
4. Is able to provide archival tissue or newly obtained core, incisional, or excisional biopsy of a tumor lesion.
5. Has adequate organ functions.

Exclusion criteria 23

1. Has a non-HGSOC histology.
2. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
3. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
4. Has received prior treatment for any stage of OC, including radiation or systemic anticancer therapy.
5. Planned or has been administered intraperitoneal chemotherapy as first-line therapy.
6. Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-immunoglobulin-like transcript 4 (ILT4), or anti-human leukocyte antigen (HLA)-G agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
7. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
8. Is currently participating in or has participated in a study of an investigational agent 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 (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
10. Has known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis.
11. Has severe hypersensitivity to pembrolizumab, carboplatin, paclitaxel (or docetaxel, if applicable),Avastin or biosimilar (if using) and/or any of their excipients.
12. Has an active autoimmune disease that has required systemic treatment in past 2 years.
13. Has an active infection requiring systemic therapy.
14. Has a known history of human immunodeficiency virus (HIV) infection.
15. Has a known history of hepatitis B or known active hepatitis C virus infection.
16. Has received colony-stimulating factors within 4 weeks prior to receiving study intervention on Day 1of Cycle 1.
17. Has had surgery <6 months prior to Screening to treat borderline ovarian tumors, early-stage OC, or early-stage fallopian tube cancer.
18. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
19. Has current, clinically relevant bowel obstruction.
20. Has a history of hemorrhage, hemoptysis, or active gastrointestinal (GI) bleeding within 6 months prior to randomization.
21. Has uncontrolled hypertension.
22. Has had an allogenic tissue/solid organ transplant.
23. Has either had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA)

Secondary endpoints 5

1. Change from Baseline in Neoadjuvant ctDNA
2. Pathological Complete Response (pCR) Rate
3. Chemotherapy Response Score (CRS)
4. Number of Participants Who Experienced an Adverse Event (AE)
5. Number of Participants Who Discontinued Study Treatment Due to an AE

Investigational products

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

Test 2

Auxiliary 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

Steven Townson

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Steven Townson

Third parties 9

Locations

4 EU/EEA countries · 15 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

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

Application history

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