A Study of Pembrolizumab (MK-3475) in Relapsed or Refractory Classical Hodgkin's Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) (MK-3475-B68)

Hodgkin's Lymphoma Clinical Trial

Official title:

A Phase 2 Study of Pembrolizumab (MK-3475) Every 6 Weeks (Q6W) in Participants With Relapsed or Refractory Classical Hodgkin's Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04875195
• Other study ID #: 3475-B68
• Secondary ID: MK-3475-B682020-
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 7, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to evaluate the objective response rate (ORR), by cohort, rrcHL and rrPMBCL, as assessed by the investigator according to Lugano classification criteria 2014 in participants treated with pembrolizumab Q6W.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 66
• Est. completion date: December 31, 2025
• Est. primary completion date: December 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have a histologically confirmed diagnosis of cHL or PMBCL, according to the World Health Organization (WHO) classification [Swerdlow, S. H., et al 2008].

• 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.

PMBCL-Specific Disease Characteristics:

• Have relapsed or refractory PMBCL and:

• Have relapsed after auto-stem cell transplant (SCT) or have failed to achieve a CR or PR within 60 days of auto-SCT. Participants may have received intervening therapy after auto-SCT for relapsed or refractory disease, in which case they must have relapsed after or be refractory to their last treatment.

OR

• For participants who are ineligible for auto-SCT, have received at least =2 lines of prior therapy and have failed to respond to or relapsed after their last line of treatment. At least 1 of the prior lines of therapy must contain a rituximab-based regimen.

Note: Participants should not need urgent cytoreductive therapy.

• Relapsed Disease: disease progression after achieving an overall response of PR or CR in response to the most recent therapy

• Refractory Disease: failure to achieve CR or PR to the most recent therapy.

cHL-Specific Disease Characteristics:

• Have relapsed or refractory cHL and:

• 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.

OR

• Have received at least =1 line of prior multiagent therapy with/without brentuximab vedotin (excluding radiation) or auto-SCT for cHL and have failed to respond to or relapsed after their last line of treatment.

• Relapsed Disease: disease progression after achieving an overall response of PR or CR to the most recent therapy.

• Refractory Disease: failure to achieve CR or PR to the most recent therapy.

• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

• Is not a woman of child bearing potential (WOCBP). OR

• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), for at least 120 days after the last dose of study intervention.

• Submit an evaluable core lymph node biopsy for biomarker analysis from an archival (>60 days) or newly obtained (within 30 days) core or incisional biopsy at Screening which was not previously irradiated. Note: If no archival tissue is available, 2 new fresh core needle samples are required.

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

• Life expectancy >3 months.

• Adequate organ function.

Exclusion Criteria:

• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic SCT within the last 5 years

• 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

• Has pericardial effusion or clinically significant pleural effusion

• 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

• 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

• 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

• 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)

• Has received prior chimeric antigen receptor T-cell (CAR-T) therapy

• 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

• 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

• Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug

• 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

• 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

• Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma

• Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients

• 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

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

• Has an active infection requiring systemic therapy

• Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority

• Has a known history of Hepatitis B (defined as hepatitis B surface antigen (HBsAg) reactive) or known active Hepatitis C virus infection

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin's Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Primary Mediastinal Large B-cell Lymphoma (PMBCL)

Intervention

Biological:
• Pembrolizumab
Pembrolizumab, 400 mg, Q6W, intravenous (IV) infusion.

Locations

Country	Name	City	State
Brazil	Fundação Pio XII - Hospital de Câncer de Barretos ( Site 1701)	Barretos	Sao Paulo
Brazil	Hospital Erasto Gaertner ( Site 1703)	Curitiba	Parana
Canada	Cross Cancer Institute ( Site 0207)	Edmonton	Alberta
Czechia	Fakultni nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0302)	Brno	Brno-mesto
Czechia	Fakultni nemocnice Hradec Kralove-IV. interni hematologicka klinika ( Site 0304)	Hradec Kralove
Czechia	Fakultni nemocnice Kralovske Vinohrady-Interni hematologicka klinika ( Site 0303)	Prague	Praha 10
France	Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand ( Site 0401)	Dijon	Cote-d Or
France	Gustave Roussy ( Site 0402)	Villejuif	Ile-de-France
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0503)	Napoli
Italy	Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO-EMATOLOGIA I ( Site 0507)	Palermo	Sicilia
Italy	Fondazione IRCCS Policlinico San Matteo ( Site 0509)	Pavia	Lombardia
Poland	Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0063)	Gdansk	Pomorskie
Poland	Pratia MCM Krakow ( Site 0064)	Krakow	Malopolskie
Poland	Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu M-Oddzial Hematologii i Transplantacji S	Poznan	Wielkopolskie
Russian Federation	Moscow City Clinical Hospital S.P. Botkin ( Site 0803)	Moscow	Moskva
Russian Federation	The National Medico-Surgical Center N.I. Pirogov ( Site 0801)	Moscow	Moskva
Russian Federation	Almazov National Medical Research Centre ( Site 0807)	Saint Petersburg	Sankt-Peterburg
South Africa	Groote Schuur Hospital ( Site 0906)	Cape Town	Western Cape
South Africa	Netcare Pretoria East Hospital-Albert Alberts Stem Cell Transplant Centre ( Site 0902)	Centurion	Gauteng
South Africa	Wits Clinical Research ( Site 0904)	Johannesburg	Gauteng
Turkey	Ankara University Department of Hematology, Clinical Research Unit ( Site 1101)	Ankara
Turkey	Ege University Medicine of Faculty ( Site 1105)	Bornova	Izmir
Ukraine	CNPE Regional Center of Oncology ( Site 1305)	Kharkiv	Kharkivska Oblast
Ukraine	National Cancer Institute ( Site 1303)	Kyiv	Kyivska Oblast
United States	Anne Arundel Medical Center-Anne Arundel Oncology and Hematology ( Site 0125)	Annapolis	Maryland
United States	Tulane Medical Center ( Site 0110)	New Orleans	Louisiana
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Czechia,  France,  Italy,  Poland,  Russian Federation,  South Africa,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) per Lugano Classification as Assessed by Investigator	ORR is defined as the percentage of the participants who had complete response (CR) or partial response (PR) and will be evaluated using computed tomography (CT) and metabolic imaging (fluorodeoxyglucose- positron emission tomography (FDG-PET)), and clinical information. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to =5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (=50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). The percentage of participants treated with pembrolizumab Q6W, by cohort, rrcHL and rrPMBCL, who experience CR or PR as assessed by investigator will be presented.	Up to approximately 40 months
Secondary	Objective Response Rate (ORR) per Lugano Classification as Assessed by Blinded Independent Central Review (BICR)	ORR is defined as the percentage of the participants who had complete response (CR) or partial response (PR) and will be evaluated using computed tomography (CT) and metabolic imaging (fluorodeoxyglucose- positron emission tomography (FDG-PET)), and clinical information. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to =5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (=50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). The percentage of participants treated with pembrolizumab Q6W, by cohort, rrcHL and rrPMBCL, who experience CR or PR as assessed by BICR will be presented.	Up to approximately 40 months
Secondary	Duration of Response (DOR) per Lugano Classification as Assessed by Investigator	For participants who demonstrate a CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. Participants will be evaluated using CT and metabolic imaging (FDG-PET), and clinical information. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to =5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (=50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). DOR as assessed by investigator will be presented among participants who demonstrated CR or PR on treatment with pembrolizumab Q6W, by cohort, rrcHL and rrPMBCL.	Up to approximately 40 months
Secondary	Duration of Response (DOR) per Lugano Classification as Assessed by BICR	For participants who demonstrate a CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. Participants will be evaluated using CT and metabolic imaging (FDG-PET), and clinical information. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to =5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (=50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). DOR as assessed by BICR will be presented among participants who demonstrated CR or PR on treatment with pembrolizumab Q6W, by cohort, rrcHL and rrPMBCL.	Up to approximately 40 months
Secondary	Area Under the Curve (AUC) of Pembrolizumab	Area under the plasma-time curve.	Predose 0-4 hours on Cycle1 Day1, Cycle2 Day1, Cycle4 Day1, Cycle5 Day1, Cycle7 Day1, Cycle9 Day1, Cycle13 Day1, Cycle17 Day1 and end of infusion on Cycle1 Day1, Cycle4 Day1 and anytime on Cycle1 Day22 and Cycle4 Day22 (cycle length = 6 weeks)
Secondary	Maximum Serum Concentration (Cmax) of Pembrolizumab	Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.	Predose 0-4 hours on Cycle1 Day1, Cycle2 Day1, Cycle4 Day1, Cycle5 Day1, Cycle7 Day1, Cycle9 Day1, Cycle13 Day1, Cycle17 Day1 and end of infusion on Cycle1 Day1, Cycle4 Day1 and anytime on Cycle1 Day22 and Cycle4 Day22 (cycle length = 6 weeks)
Secondary	Minimum Serum Concentration (Cmin) of Pembrolizumab	Cmin is a measure of the minimum amount of drug in the plasma after the dose is given.	Predose 0-4 hours on Cycle1 Day1, Cycle2 Day1, Cycle4 Day1, Cycle5 Day1, Cycle7 Day1, Cycle9 Day1, Cycle13 Day1, Cycle17 Day1 and end of infusion on Cycle1 Day1, Cycle4 Day1 and anytime on Cycle1 Day22 and Cycle4 Day22 (cycle length = 6 weeks)
Secondary	Antidrug Antibody Levels (ADA) for Pembrolizumab	ADA response to pembrolizumab at the beginning of each of the first 5 cycles will be determined.	Predose 0-4 hours on Cycle1 Day1, Cycle2 Day1, Cycle4 Day1, Cycle5 Day1, Cycle7 Day1, Cycle9 Day1, Cycle13 Day1, Cycle17 Day1 and end of infusion on Cycle1 Day1, Cycle4 Day1 and anytime on Cycle1 Day22 and Cycle4 Day22 (cycle length = 6 weeks)
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 30 months
Secondary	Number of Participants Who Discontinued Study Treatment Due to AE	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 27 months

External Links

•   Merck Clinical Trials Information