A Study of MK-1088 as monotherapy and in combination with pembrolizumab in patients with advanced 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

29 Jun 2022 → 7 Sep 2023

Decision date (initial)

2023-02-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-502288-40-00

EudraCT number

2021-006712-93

WHO UTN

U1111-1284-0024

ClinicalTrials.gov

NCT05394350

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacodynamic, Therapy, Efficacy, Safety, Pharmacokinetic

To determine the safety and tolerability and to establish a preliminary maximum tolerated dose/recommended Phase 2 dose of MK-1088 administered as monotherapy and in combination with pembrolizumab infusion in Part 1

Secondary objectives 2

1. To evaluate the PK of MK-1088 administered as monotherapy and in combination with pembrolizumab infusion in Part 1 and in Part 2
2. To evaluate the antitumor activity (objective response rate [ORR] based on PCWG-modified RECIST 1.1 [prostate cancer participants only] or RECIST 1.1 [all other participants]) of MK-1088 as assessed by the investigator when used as monotherapy and in combination with pembrolizumab in Part 1 and in Part 2

Conditions and MedDRA coding

Treatment of advanced/metastatic solid tumors

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Has a histologically- or cytologically-confirmed diagnosis of advanced/metastatic solid tumor by pathology report and have received, have been intolerant to, or have been ineligible for treatment known to confer clinical benefit
2. For metastatic castrate-resistant prostate cancer (mCRPC) only: (1) Must have previously received docetaxel, prior treatment with one other chemotherapy is allowed as well as up to 2 second-generation hormonal manipulations and (2) have prostate cancer progression within 6 months before screening, as determined by the investigator
3. If human immunodeficiency virus (HIV) positive, has well-controlled HIV on anti-retroviral therapy (ART)

Exclusion criteria 18

1. Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention
2. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
3. Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
4. Has an active infection requiring therapy
5. Has a history of interstitial lung disease
6. Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
7. Has an active autoimmune disease that has required systemic treatment in the past 2 years
8. Has concurrent active Hepatitis B and Hepatitis C virus infection
9. Has HIV with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
10. Has not fully recovered from any effects of major surgery without significant detectable infection
11. Has a history or current evidence of a gastrointestinal (GI) condition or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
12. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
13. Has a QTcF >470 msec
14. Has history of an allogeneic stem cell transplant or a solid organ transplant
15. Has received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
16. Has received prior radiotherapy within 2 weeks of start of study intervention, or had radiation-related toxicities requiring corticosteroids
17. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
18. Has a "superscan" bone scan

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
2. Number of Participants Experiencing Adverse Events (AEs
3. Number of Participants Discontinuing Study Treatment Due to AEs

Secondary endpoints 4

1. Area Under the Plasma Concentration-Time Curve (AUC) of MK-1088
2. Maximum Plasma Concentration (Cmax) of MK-1088
3. Minimum Plasma Concentration (Cmin) of MK-1088
4. Objective Response Rate (ORR)

Investigational products

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

Test 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

Julia Wanda Cohen

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Julia Wanda Cohen

Third parties 3

Locations

1 EU/EEA country · 3 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 3 files

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

Application history

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