MK-4280 and Pembrolizumab in Hematologic Malignancies

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

20 Mar 2019 → 28 Jan 2026

Decision date (initial)

2023-10-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-503587-17-00

EudraCT number

2018-001461-16

WHO UTN

U1111-1287-5405

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. To determine the safety and tolerability and to establish a preliminary recommended Phase2 dose (RP2D) of MK-4280 when used in combination with pembrolizumab.
2. To determine the safety and tolerability of MK-4280 monotherapy.
3. To determine the safety and tolerability of pembrolizumab monotherapy.

Secondary objectives 3

1. To evaluate the objective response rate (ORR) of MK-4280 as assessed by the investigator when used in combination with pembrolizumab. Assessment will be based on the International Working Group (IWG) 2007 (Cheson) Lymphoma Disease Response criteria.
2. To evaluate the ORR of MK-4280 monotherapy as assessed by the investigator. Assessment will be based on Lugano.
3. To evaluate the ORR of pembrolizumab monotherapy as assessed by the investigator. Assessment will be based on Lugano.

Conditions and MedDRA coding

Hematologic malignancies

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Has measurable disease, defined as ≥1 lesion that can be accurately measured in 2 dimensions with diagnostic quality cross sectional anatomic imaging (computed tomography or magnetic resonance imaging). Minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis
2. Is able to provide a core or excisional tumor biopsy for biomarker analysis from an archival (within 3 months) or newly obtained biopsy at screening
3. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)

Exclusion criteria 17

1. Has known clinically active central nervous system (CNS) involvement
2. Has received prior therapy with an anti-lymphocyte activation gene-3 (LAG-3) antibody
3. Has received chimeric antigen receptors (CAR)-T-cell therapy for classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) Cohorts
4. Has received prior anticancer therapy or thoracic radiation therapy within 14 days before the first dose of study treatment
5. Has ≥Grade 2 non-hematological residual toxicities from prior therapy
6. Has had a prior anticancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to agents administered ≥4 weeks earlier
7. Has received a live vaccine within 30 days prior to first dose of study treatment. Administration of killed vaccines are allowed
8. Has received an investigational agent or used an investigational device within 4 weeks prior to intervention administration
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
10. Has a known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
11. Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
12. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
13. Has an active infection requiring intravenous systemic therapy
14. Has a known history of human immunodeficiency virus (HIV) infection
15. Has known, active hepatitis B or hepatitis C infection
16. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
17. Has had an allogeneic hematopoetic stem cell/solid organ transplantation within the last 5 years

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)
2. Percentage of Participants Experiencing an Adverse Event (AE)
3. Percentage of Participants with Treatment Discontinuations Due to an AE

Secondary endpoints 1

1. Objective Response Rate (ORR)

Investigational products

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

Test 2

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

Pallavi Pillai

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Pallavi Pillai

Third parties 5

Locations

4 EU/EEA countries · 10 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 36 files

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

Application history

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