Clinical trial NCT04875195: 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)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hodgkin's Lymphoma
Primary Mediastinal Large B-cell Lymphoma (PMBCL)
Keywords: PD1
PD-1
PDL1
PD-L1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-05-06
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 every six weeks (Q6W).


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR) Per Lugano Classification as Assessed by Investigator
timeFrame: Up to approximately 30 months
Secondary outcomes:
measure: ORR Per Lugano Classification as Assessed by Blinded Independent Central Review (BICR)
timeFrame: Up to approximately 30 months
measure: Duration of Response (DOR) Per Lugano Classification as Assessed by Investigator
timeFrame: Up to approximately 54 months
measure: DOR Per Lugano Classification as Assessed by BICR
timeFrame: Up to approximately 54 months
measure: Area Under the Curve (AUC) Early Cycle of Pembrolizumab
timeFrame: Predose on Day 1 and Day 42 of Cycle 1 (cycle length=6 weeks)
measure: Area Under the Curve (AUC) Steady State of Pembrolizumab
timeFrame: Predose on Day 1 and Day 42 of Cycle 4 (cycle length=6 weeks)
measure: Maximum Serum Concentration (Cmax) Early Cycle of Pembrolizumab
timeFrame: Predose on Day 1 of Cycle 1 and end of infusion on Day 1 of Cycle 1 (cycle length = 6 weeks)
measure: Maximum Serum Concentration (Cmax) Steady State of Pembrolizumab
timeFrame: Predose on Day 1 of Cycle 4, and end of infusion on Day 1 of Cycle 4 (cycle length = 6 weeks)
measure: Trough Serum Concentration (Ctrough) Early Cycle of Pembrolizumab
timeFrame: Predose on Day 1 of Cycle 1 and Day 42 of Cycle 1 (cycle length = 6 weeks)
measure: Trough Serum Concentration (Ctrough) Steady State of Pembrolizumab
timeFrame: Predose on Day 1 of Cycle 1 and Day 42 of Cycle 4 (cycle length = 6 weeks)
measure: Antidrug Antibody Levels (ADA) for Pembrolizumab
timeFrame: 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)
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 54 months
measure: Number of Participants Who Discontinued Study Treatment Due to AE
timeFrame: Up to approximately 54 months
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site
state: California
city: New Orleans
country: United States
facility: Tulane Medical Center ( Site 0110)
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Medical Center-Anne Arundel Oncology and Hematology ( Site 0125)
state: Maryland
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner ( Site 1703)
state: Parana
city: Barretos
country: Brazil
facility: Fundação Pio XII - Hospital de Câncer de Barretos ( Site 1701)
state: Sao Paulo
city: Edmonton
country: Canada
facility: Cross Cancer Institute ( Site 0207)
state: Alberta
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0302)
state: Brno-mesto
city: Prague
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady-Interni hematologicka klinika ( Site 0303)
state: Praha 10
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove-IV. interni hematologicka klinika ( Site 0304)
city: Dijon
country: France
facility: Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand ( Site 0401)
state: Cote-d Or
city: Villejuif
country: France
facility: Gustave Roussy ( Site 0402)
state: Ile-de-France
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo ( Site 0509)
state: Lombardia
city: Palermo
country: Italy
facility: Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO-EMATOLOGIA I ( Site 0507)
state: Sicilia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0503)
city: Krakow
country: Poland
facility: Pratia MCM Krakow ( Site 0064)
state: Malopolskie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0063)
state: Pomorskie
city: Poznan
country: Poland
facility: Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu M-Oddzial Hematologii i Transplantacji S
state: Wielkopolskie
city: Moscow
country: Russian Federation
facility: The National Medico-Surgical Center N.I. Pirogov ( Site 0801)
state: Moskva
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital S.P. Botkin ( Site 0803)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre ( Site 0807)
state: Sankt-Peterburg
city: Centurion
country: South Africa
facility: Netcare Pretoria East Hospital-Albert Alberts Stem Cell Transplant Centre ( Site 0902)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Clinical Research ( Site 0904)
state: Gauteng
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital ( Site 0906)
state: Western Cape
city: Bornova
country: Turkey
facility: Ege University Medicine of Faculty ( Site 1105)
state: Izmir
city: Ankara
country: Turkey
facility: Ankara University Department of Hematology, Clinical Research Unit ( Site 1101)
city: Kharkiv
country: Ukraine
facility: CNPE Regional Center of Oncology ( Site 1305)
state: Kharkivska Oblast
city: Kyiv
country: Ukraine
facility: National Cancer Institute ( Site 1303)
state: Kyivska Oblast
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: