A Phase 2 Study of MK-4280A for the Treatment of Selected Solid Tumors

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

27 Mar 2024 → 13 Mar 2026

Decision date (initial)

2023-10-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-505022-34-00

WHO UTN

U1111-1290-7288

ClinicalTrials.gov

NCT06036836

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

1. Cohort A: To evaluate clinical benefit in participants treated with MK-4280A or pembrolizumab

2. Cohort B: To evaluate lenvatinib in combination with MK-4280A or pembrolizumab with respect to objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator

Secondary objectives 5

1. Cohort A: To evaluate pathologic complete response (pCR) rate of MK-4280A or pembrolizumab as assessed by local pathology review
2. Cohort A: To evaluate Major Pathologic Response (mPR) rate as assessed by local pathology review
3. Cohort A: To evaluate the OR rate of participants treated with MK-4280A or pembrolizumab per RECIST 1.1 as assessed by investigator prior to surgical resection
4. Cohort A: To evaluate the safety and tolerability of MK-4280A followed by surgery
5. Cohort B: To evaluate the safety and tolerability of MK-4280A in combination with lenvatinib

Conditions and MedDRA coding

Neoplasm malignant

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Histologically confirmed diagnosis of resectable cutaneous squamous cell carcinoma cSCC as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted) - Cohort A
2. Stage II to Stage IV disease without M1. cSCC tumors arising in the head and neck will be staged according to AJCC Ed. 8 and cSCC tumors arising in non-head and neck locations will be staged according to UICC Ed. 8. - Cohort A
3. Is systemic treatment naïve. - Cohort A
4. Archival tumor tissue sample, or newly obtained surgical resection, or biopsy sample of a tumor lesion not previously irradiated has been provided - Cohort A
5. Is an individual of any sex/gender, at least 18 years of age at the time of providing the informed consent - Cohort A
6. Histologically confirmed diagnosis of EC that is not dMMR (pMMR) as documented by a local test report. - Cohort B
7. Documented evidence of stage IVB (per 2009 International Federation of Gynecology and Obstetrics (FIGO) staging), recurrent, or metastatic EC, and are not candidates for curative surgery or radiation - Cohort B
8. Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC in any setting - Cohort B
9. Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) by investigator (before first dose of study intervention) - Cohort B
10. Is assigned female sex at birth, at least 18 years of age at the time of providing the informed consent - Cohort B
11. Has adequately controlled blood pressure without antihypertensive medication - Cohort B
12. Agrees to follow contraception guidelines if a participant of childbearing potential
13. Has a life expectancy >3 years per investigator assessment
14. Has adequate organ function
15. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
16. If positive for hepatitis B, has received antiviral therapy for ≥4 weeks and undetectable viral load prior to randomization
17. If positive for hepatitis C, has undetectable viral load at screening
18. If positive for human immunodeficiency virus (HIV), has well-controlled HIV on a stable highly active antiretroviral therapy

Exclusion criteria 10

1. Has known hypersensitivity to active substances or their excipients including previous clinically significant hypersensitivity reaction to treatment with other monocloncal antibody (mAb)
2. History of allogeneic tissue/solid organ transplant
3. Received prior radiotherapy to the index lesion (in-field lesion) - Cohort A
4. Participants for whom the primary site of cSCC was anogenital area (penis, scrotum, vulva, perianal region) are not eligible - Cohort A
5. Has had major surgery within 3 weeks prior to first dose of study interventions - Cohort B
6. Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula - Cohort B
7. Has urine protein ≥1 g/24 hours - Cohort B
8. Has a left ventricle ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO) - Cohort B
9. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation - Cohort B
10. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention - Cohort B

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Clinical Benefit - Cohort A
2. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Investigator – Cohort B

Secondary endpoints 7

1. Pathologic Complete Response (pCR) – Cohort A
2. Major Pathologic Response (mPR) - Cohort A
3. ORR per RECIST 1.1 as assessed by Investigator - Cohort A
4. Number of participants with an adverse event (AE) - Cohorts A and B
5. Number of participants discontinuing from study therapy due to AE - Cohorts A and B
6. Number of participants experiencing perioperative complications - Cohort A
7. Number of participants with an AE that precludes surgery - Cohort A

Investigational products

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

Test 1

Comparator 3

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

Roman Groisberg

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Roman Groisberg

Third parties 7

Locations

4 EU/EEA countries · 14 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 43 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