Phase 2 study of Pembrolizumab given every 6 weeks to participants diagnosed with Relapsed or Refractory Classical Hodgkin’s Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)

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

27 May 2021 → 13 Oct 2025

Decision date (initial)

2024-07-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2024-510979-38-00

EudraCT number

2020-005609-20

WHO UTN

U1111-1302-8634

ClinicalTrials.gov

NCT04875195

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. To evaluate objective response rate (ORR), by cohort, rrcHL and rrPMBCL, as assessed by the investigator according to Lugano classification criteria [Cheson, B. D., et al 2014] in individuals treated with pembrolizumab Q6W.

Secondary objectives 5

1. To evaluate objective response rate (ORR), by cohort, rrcHL and rrPMBCL, as assessed by blinded independent central review (BICR) according to Lugano classification criteria [Cheson, B. D., et al 2014] in individuals treated with pembrolizumab Q6W.
2. To evaluate duration of response (DOR), by cohort, rrcHL and rrPMBCL, as assessed by the investigator according to Lugan classification criteria [Cheson, B. D., et al 2014] in individuals treated with pembrolizumab Q6W.
3. To evaluate duration of response (DOR), by cohort, rrcHL and rrPMBCL, as assessed by BICR according to Lugano classification criteria [Cheson, B. D., et al 2014] in individuals treated with pembrolizumab Q6W.
4. To evaluate the pharmacokinetic (PK) profile, immunogenicity of pembrolizumab 400 mg Q6W.
5. To evaluate the safety and tolerability of pembrolizumab Q6W.

Conditions and MedDRA coding

Relapsed or refractory Classical Hodgkins Lymphoma and relapsed or refractory Primary Mediastinal Large B-cell Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Have a histologically confirmed diagnosis of cHL or PMBCL, according to the World Health Organization (WHO) classification
2. Has radiographically measurable cHL or PMBCL disease as per Lugano classification with at least 1 nodal lesion (which has not been previously radiated) that is >15 mm in long axis, regardless of the length of the short axis, and/or extranodal lesion of >10 mm in long and short axis
3. PMBCL-Specific Disease Characteristics: • Have relapsed or refractory PMBCL and: • Have relapsed after auto-stem cell transplant (SCT)
4. cHL-Specific Disease Characteristics: • Have relapsed or refractory cHL • Have relapsed during their last cHL regimen after receiving at least 2 cycles of therapy or within 12 months after completing the last regimen for cHL

Exclusion criteria 20

1. Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic SCT within the last 5 years
2. Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication
3. Has pericardial effusion or clinically significant pleural effusion
4. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers
5. Is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) <3 days prior to the first dose of study intervention. Note: Participants who receive daily steroid replacement therapy are an exception
6. Has 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 adverse event (AEs) due to agents administered more than 4 weeks earlier
7. Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137)
8. Has received prior chimeric antigen receptor T-cell (CAR-T) therapy
9. Has received prior systemic anticancer therapy, or radiotherapy, including investigational agents within 4 weeks prior to the first dose of study intervention. Note: If the participant had a major operation, the participant must have recovered adequately from the procedure and/or any complications from the operation before starting study intervention
10. Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis. Participants must have recovered from all radiation-related toxicities, and not require corticosteroids
11. Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
12. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
13. 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 to the first dose of study medication
14. Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma
15. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
16. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
17. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
18. Has an active infection requiring systemic therapy
19. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
20. Has a known history of Hepatitis B (defined as hepatitis B surface antigen (HBsAg) reactive) or known active Hepatitis C virus infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR) per Lugano Classification as Assessed by Investigator

Secondary endpoints 9

1. Objective Response Rate (ORR) per Lugano Classification as Assessed by Blinded Independent Central Review (BICR)
2. Duration of Response (DOR) per Lugano Classification as Assessed by Investigator
3. Duration of Response (DOR) per Lugano Classification as Assessed by BICR
4. Area Under the Curve (AUC) of Pembrolizumab
5. Maximum Serum Concentration (Cmax) of Pembrolizumab
6. Minimum Serum Concentration (Cmin) of Pembrolizumab
7. Antidrug Antibody Levels (ADA) for Pembrolizumab
8. Number of Participants Who Experienced an Adverse Event (AE)
9. Number of Participants Who Discontinued Study Treatment Due to AE

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 8

Locations

3 EU/EEA countries · 9 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

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