A clinical study of MK-5684 in people with certain solid tumors (MK-5684-015)

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

2 Sep 2025 → ongoing

Decision date (initial)

2025-08-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2024-519563-18-00

WHO UTN

U1111-1315-5430

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenomic, Efficacy, Pharmacodynamic, Pharmacokinetic, Pharmacogenetic

1. To compare MK-5684 to standard of care (SOC) with respect to 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) in participants with selected solid tumors (All Cohorts).

Secondary objectives 5

1. To evaluate MK-5684 to SOC with respect to overall survival (OS) in participants with selected solid tumors (All Cohorts).
2. To evaluate MK-5684 to SOC with respect to clinical benefit rate (CBR) per RECIST 1.1 as assessed by BICR in participants with breast cancer (Cohort A).
3. To evaluate MK-5684 to SOC with respect to objective response rate (ORR) per RECIST 1.1 as assessed by BICR in participants with selected solid tumors (All Cohorts).
4. To evaluate MK-5684 with respect to duration of response (DOR) per RECIST 1.1 as assessed by BICR in participants with selected solid tumors (All Cohorts).
5. To evaluate the safety and tolerability of MK-5684 in participants with selected solid tumors (All Cohorts).

Conditions and MedDRA coding

Breast cancer, Ovarian cancer, Endometrial 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 10

1. (Cohort A) Has a diagnosis of hormone receptor positive/Human Epidermal Growth Factor Receptor 2 negative invasive breast carcinoma that is either locally advanced disease not amenable to resection with curative intent (herein called unresectable) or metastatic disease not treatable with curative intent.
2. (Cohort A) Has experienced disease progression on or after at least 1 prior endocrine-based therapy in the metastatic setting.
3. (Cohort B) Has histologically confirmed high-grade epithelial (including high-grade serous or predominantly serous, high-grade endometrioid, malignant mixed Müllerian tumors [carcinosarcoma], or clear cell) ovarian, fallopian tube, or primary peritoneal carcinoma.
4. (Cohort B) Has received between 4 to 8 cycles of platinum-based doublet chemotherapy in third-line setting for ovarian cancer.
5. (Cohort C) Histologically confirmed diagnosis of primary advanced or recurrent low-grade endometrioid carcinoma (eg, Federation of Gynecology and Obstetrics [FIGO] Grade 1/2, or well/moderately differentiated).
6. (Cohort C) Treatment naïve or has received up to 1 prior line of platinum-based therapy in either the advanced/metastatic OR adjuvant/neoadjuvant setting.
7. Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline.
8. Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
9. Participants who are Hepatitis B surface antigen positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load.
10. Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.

Exclusion criteria 16

1. (Cohort A) Breast cancer amenable to treatment with curative intent.
2. (Cohort A) Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications, such as lymphangitic lung metastases, radiographic evidence of intratumoral cavitation or invasion/infiltration of a major blood vessel, bone marrow replacement, carcinomatous meningitis, significant symptomatic liver metastases, symptomatic pericardial effusion, symptomatic peritoneal carcinomatosis, or the need to achieve rapid symptom control.
3. (Cohort B) Has nonepithelial cancers (germ cell tumors and sex cord-stromal tumors), borderline tumors (low malignant potential), mucinous, seromucinous that is predominantly mucinous, malignant Brenner’s tumor, low-grade serous, low-grade endometrioid, and undifferentiated carcinoma.
4. (Cohorte B)Has platinum-resistant ovarian cancer (defined as disease that has progressed per radiographic imaging within 180 days after the last dose of first-line [1L] platinum-based therapy) or platinum-refractory ovarian cancer (defined as disease that has progressed per radiographic imaging while receiving or within 28 days of the last dose of 1L platinum based therapy).
5. (Cohort B) Is a candidate for curative-intent surgery or curative-intent radiotherapy for ovarian cancer.
6. (Cohort C) Has high-grade (FIGO Grade 3 or poorly differentiated) endometroid carcinoma and nonendometrioid histologies of any type (including serous, clear cell, mixed, carcinosarcoma), and neuroendocrine tumors are not eligible. Uterine mesenchymal tumors such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas, and adenosarcomas are not eligible.
7. (Cohorte C) Is a candidate for curative-intent surgery or curative-intent radiotherapy.
8. Has confirmed or suspected adrenal metastases.
9. Has known difficulty in tolerating oral medications, unable to swallow orally administered medication, or conditions which would impair absorption of oral medications.
10. Has any prior history or current condition of adrenal insufficiency.
11. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.
12. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
13. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
14. Has known active central nervous system metastases and/or carcinomatous meningitis.
15. Has a history of stem cell/solid organ transplant.
16. Has not adequately recovered from major surgery or has ongoing surgical complications.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival (PFS) – All Cohorts

Secondary endpoints 6

1. Overall Survival (OS) – All Cohorts
2. Clinical Benefit Rate (CBR) – Cohort A
3. Objective Response Rate (ORR) – All Cohorts
4. Duration of Response (DOR) – All Cohorts
5. Number of Participants who Experience One or More Adverse Events (AEs) – All Cohorts
6. Number of Participants who Discontinue Study Intervention Due to an AE – All Cohorts

Investigational products

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

Test 1

Comparator 6

Auxiliary 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, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

​Yingjie Liu

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

​Yingjie Liu

Third parties 8

Locations

1 EU/EEA country · 5 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

Urgent safety measures 1 · Art. 54 CTR

Results and documents

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

Documents 17 files

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

Application history

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