Phase 1b study to evaluate MK 0482 for Relapsed/Refractory AML/CMML

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

16 May 2023 → 12 Dec 2023

Decision date (initial)

2023-07-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-503580-42-00

EudraCT number

2022-003740-27

WHO UTN

U1111-1287-5269

ClinicalTrials.gov

NCT05038800

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic, Pharmacokinetic, Safety, Efficacy

To determine the safety and tolerability and to determine a preliminary recommended Phase 2 dose of MK-0482 monotherapy

Secondary objectives 2

1. To characterize the pharmacokinetic (PK) profile of MK-0482 monotherapy
2. To evaluate antileukemia activity of MK-0482 monotherapy in acute myeloid leukemia (AML)

Conditions and MedDRA coding

Active CNS leukemia.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Has confirmed diagnosis of Acute Myeloid Leukemia (AML) with myelomonocytic or monoblastic/monocytic differentiation per World Health Organization (WHO) 2016 criteria and with confirmed refractory or relapsed disease (i.e., ≥5% blast in bone marrow or in peripheral blood) after treatment with available therapies known to benefit participant's AML subtypes or has a known diagnosis of Chronic Myelomonocytic Leukemia (CMML) per WHO criteria [2017] with confirmed refractory or released disease after treatment with available therapies known to be active for CMML.

Exclusion criteria 17

1. Has active central nervous system (CNS) leukemia.
2. Has isolated extramedullary disease, i.e., no leukemic involvement in bone marrow or peripheral blood.
3. Has diagnosis of acute promyelocytic leukemia or participants with known Philadelphia chromosome positive (Ph+) AML.
4. Has received previous allogeneic stem cell transplant or organ transplant within 60 days of the start of study treatment.
5. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 1 year.
6. Has a history of any of the following cardiovascular conditions within 6 months of screening: myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, coronary artery bypass graft, or pulmonary embolism; has New York Heart Association (NYHA) Class III or IV congestive heart failure.
7. Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAB) and or any components of the study intervention, MK-0482.
8. Has an active uncontrolled infection requiring directed therapy.
9. Has immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, or disseminated intravascular coagulation.
10. Has known human immunodeficiency virus (HIV) and/or hepatitis B or C infections, or is known to be positive for HBsAg/ Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) or hepatitis C antibody or Ribonucleic acid (RNA).
11. Has known psychiatric or substance abuse disorders (verbally reported) that would interfere with the participant's ability to cooperate with the requirements of the study.
12. Is pregnant or breast feeding 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 intervention.
13. Has received systemic anticancer therapy, radiotherapy, or surgery within 2 weeks before the start of study treatment.
14. Has received hematopoietic cytokines (Granulocyte Colony Stimulating Factor (G-CSF), Granulocyte Macrophage (GM)-CSF, or erythropoietin) within 2 weeks prior to start of study treatment.
15. Has received a live or live attenuated vaccine within 30 days before the first dose of study medication.
16. Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 14 days of administration of MK-0482.
17. Has a 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Number of participants who experience a dose-limiting toxicity (DLT)
2. Number of participants who experience at least one adverse event (AE)
3. Number of participants who discontinue study treatment due to an AE

Secondary endpoints 5

1. Maximum plasma concentration (Cmax)
2. Trough plasma concentration (Ctrough)
3. Complete remission (CR) rate
4. Composite CR rate
5. 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

Mei Chen

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Mei Chen

Third parties 7

Locations

1 EU/EEA country · 1 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