Clinical trial of MK-2870 in combination with pembrolizumab in people who have had surgery to treat triple negative breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Jul 2024 → ongoing

Decision date (initial)

2024-06-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-504962-52-00

WHO UTN

U1111-1289-8264

ClinicalTrials.gov

NCT06393374

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Therapy, Safety

To compare MK-2870 plus pembrolizumab to TPC (pembrolizumab or pembrolizumab plus capecitabine) with respect to iDFS per investigator assessment

Secondary objectives 4

1. To compare MK-2870 plus pembrolizumab to TPC with respect to OS
2. To evaluate MK-2870 plus pembrolizumab and TPC with respect to DRFS per investigator assessment
3. To evaluate MK-2870 plus pembrolizumab and TPC with respect to mean change from baseline in health-related QoL using the EORTC QLQ-C30 in all participants
4. To evaluate the safety and tolerability of MK-2870 plus pembrolizumab

Conditions and MedDRA coding

Triple negative breast cancer.

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Has centrally confirmed triple negative breast cancer (TNBC), as defined by the most recent American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines.
2. Has no evidence of locoregional or distant relapse, as assessed by the treating physician.
3. Had neoadjuvant treatment based on the KEYNOTE-522 regimen (pembrolizumab with carboplatin/taxanes and pembrolizumab with anthracycline-based chemotherapy) followed by surgery according to National Comprehensive Cancer Network (NCCN) and/or local treatment guidelines for TNBC.
4. Had adequate excision and surgical removal of all clinically evident disease in the breast and/or lymph nodes and have adequately recovered from surgery.
5. Has non-pathologic complete response at surgery.
6. Is able to continue on adjuvant pembrolizumab.
7. Randomization must be conducted within 16 weeks from surgical resection.
8. Completed adjuvant radiation therapy (if indicated) and recovered before randomization.
9. Has provided tissue from the surgical resection for central laboratory determination of trophoblast cell surface antigen 2 (TROP2) status.
10. If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (120 days for MK-2870 and 95 days for capecitabine [no restriction for pembrolizumab]): agrees to refrain from donating sperm AND is either abstinent and agrees to remain abstinent or uses highly effective contraception
11. For females (assigned at birth), is not pregnant or breastfeeding and ≥1 of the following applies: is not a participant of childbearing potential (POCBP) OR is a POCBP and uses highly effective contraception after the last dose of study intervention (210 days for MK-2870, 120 days for pembrolizumab, and 185 days for capecitabine). Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention.
12. Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline (except alopecia).
13. Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).
14. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before first dose of study treatment.
15. Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.

Exclusion criteria 21

1. Has a known germline breast cancer gene (BRCA) mutation (deleterious or suspected deleterious) and is eligible for adjuvant therapy with olaparib where olaparib is approved and available.
2. Has Grade >2 peripheral neuropathy.
3. History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
4. Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea).
5. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months prior to study intervention.
6. Received prior treatment with a TROP2-directed antibody drug conjugate (ADC) or a topoisomerase I inhibitor-containing ADC.
7. Received anticancer therapy in the adjuvant phase including but not limited to chemotherapy, small molecule anticancer drugs, PARP inhibitors, ADCs, and/or immunotherapy, with the exception of adjuvant radiation therapy.
8. Is currently receiving a strong inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study. The required washout period before starting MK-2870 is 2 weeks.
9. Except for pembrolizumab as neoadjuvant therapy for early-stage TNBC: Received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
10. Except for chemotherapy as neoadjuvant therapy for early-stage TNBC: Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
11. Received prior radiotherapy within 3 weeks of start of study intervention, or required corticosteroids for radiation related toxicities that cannot be discontinued before the first dose of study intervention.
12. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
13. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
14. Known additional malignancy that is progressing or has required active treatment within the past 5 years.
15. 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.
16. Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
17. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
18. Active infection requiring systemic therapy.
19. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.
20. Concurrent active Hepatitis B and Hepatitis C virus infection.
21. History of allogeneic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Invasive Disease-Free Survival (iDFS)

Secondary endpoints 8

1. Overall Survival (OS)
2. Distant Recurrence-Free Survival (DRFS)
3. Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
4. Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score
5. Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Role Functioning (Items 6 and 7) Score
6. Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue (Items 10, 12, 18) Score
7. Number of Participants Who Experience One or More Adverse Events (AEs)
8. Number of Participants Who Discontinue Study Intervention Due to an AE

Investigational products

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

Test 2

Comparator 1

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

Wilbur Pan

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Wilbur Pan

Third parties 9

Locations

15 EU/EEA countries · 121 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 140 files

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

Application history

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