Ph2 Study of MK-3475A in Hematologic Malignances in Participants with Relapsed or Refractory Classical Hodgkin Lymphoma or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma

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

30 Sep 2024 → ongoing

Decision date (initial)

2024-12-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2024-510969-42-00

WHO UTN

U1111-1302-8349

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Diagnosis, Pharmacodynamic, Efficacy, Therapy

1. To characterize the pharmacokinetics (PK) profile of pembrolizumab following subcutaneous (SC) injection of MK-3475A (Cycle 1)
2. To evaluate MK-3475A SC by cohort with respect to objective response rate (ORR) as assessed by the investigator according to Lugano classification criteria

Secondary objectives 4

1. To characterize the PK profile of pembrolizumab following SC injection of MK-3475A (steady-state, Cycle 3)
2. To evaluate the development of circulating anti-pembrolizumab antibodies following SC injection of MK-3475A
3. To evaluate the safety and tolerability of MK-3475A SC
4. To evaluate MK-3475A SC by cohort with respect to duration of response (DOR) as assessed by the investigator according to Lugano classification criteria

Conditions and MedDRA coding

Relapsed or Refractory Classical Hodgkin’s Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histologically confirmed diagnosis of classical Hodgkin lymphoma (cHL) or primary mediastinal B-cell lymphoma (PMBCL)
2. Radiographically measurable cHL or PMBCL disease assessed by investigator as per Lugano classification
3. Has a life expectancy of > 3 months
4. Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
5. Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before randomization
6. Participants with history of hepatitis C virus (HCV) infection are eligible if they have completed curative antiviral therapy at least 4 weeks before randomization and HCV viral load is undetectable at screening
7. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before or on the day of the first dose of study intervention

Exclusion criteria 16

1. Has clinically significant (ie, active) cardiovascular disease.
2. Has pericardial effusion or clinically significant pleural effusion
3. Has known additional malignancy that is progressing or has required active treatment within the past 2 years
4. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
5. Received prior monoclonal antibody within 4 weeks prior to first dose of study intervention or has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier
6. Received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor
7. Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
8. Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
9. Received a live or live-attenuated vaccine within 30 days before first dose of study intervention
10. Is receiving systemic antineoplastic chemotherapy, immunotherapy, or biological therapy not specified in this protocol
11. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
12. Active autoimmune disease that has required systemic treatment in the past 2 years
13. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
14. Active infection requiring systemic therapy except certain protocol-specified therapies
15. Concurrent active hepatitis B and hepatitis C virus infection
16. Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplant (SCT) within the last 5 years

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Maximum Concentration (Cmax) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase
2. Lowest Plasma Concentration (Ctrough) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase
3. Area Under the Concentration-Time Curve of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase from Week 0-Week 6 (AUC0-6weeks)
4. Objective Response Rate (ORR) per Lugano Classification Criteria as Assessed by Investigator

Secondary endpoints 7

1. Maximum Concentration (Cmax) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase at Steady-State
2. Lowest Plasma Concentration (Ctrough) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase at Steady-State
3. Area Under the Concentration-Time Curve of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase from Week 0-Week 6 (AUC0-6weeks) at Steady-State
4. Number of Participants with Antidrug Antibodies (ADA) Level of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase
5. Number of Participants Experiencing an Adverse Event (AE)
6. Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE)
7. Duration of Response (DOR) per Lugano Classification Criteria as Assessed by Investigator

Investigational products

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

Test 1

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

Katherine Ryland

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Katherine Ryland

Third parties 4

Locations

3 EU/EEA countries · 7 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 24 files

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

Application history

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