Clinical trial NCT02453594: Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (MK-3475-087/KEYNOTE-087)
Official title: A Phase II Clinical Trial of MK-3475 (Pembrolizumab) in Subjects With Relapsed or Refractory (R/R) Classical Hodgkin Lymphoma (cHL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Keywords: PD1
PD-1
PDL1
PD-L1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-05-25
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study of pembrolizumab (MK-3475) for participants with relapsed/refractory classical Hodgkin Lymphoma (RRcHL) who: 1) have failed to achieve a response or progressed after autologous stem cell transplant (auto-SCT) and have relapsed after treatment with or failed to respond to brentuximab vedotin (BV) post auto-SCT or 2) were unable to achieve a Complete Response (CR) or Partial Response (PR) to salvage chemotherapy and did not receive auto-SCT, but have relapsed after treatment with or failed to respond to BV or 3) have failed to achieve a response to or progressed after auto-SCT and have not received BV post auto-SCT.

The primary study hypothesis is that treatment with single agent pembrolizumab will result in a clinically meaningful overall response rate.


Eligibility criteria: Inclusion criteria:

* Relapsed or refractory de novo classical Hodgkin lymphoma
* Participant may have failed to achieve a response to, progressed after, or be ineligible for autologous stem cell transplant (auto-SCT)
* Participant may have failed to achieve a response or progressed after treatment with brentuximab vedotin or may be brentuximab vedotin naïve
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Measurable disease
* Adequate organ function

Exclusion criteria:

* Diagnosis of immunosuppression or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
* Prior monoclonal antibody within 4 weeks prior to study Day 1 or chemotherapy, targeted small molecular therapy, or radiation therapy within 2 weeks prior to study Day 1
* Prior allogeneic hematopoietic stem cell transplantation
* Known clinically active central nervous system involvement
* Known additional malignancy that is progressing or requires active treatment
* Has a known history of Human Immunodeficiency Virus (HIV)
* Has known active Hepatitis B (HBV) or Hepatitis C (HCV)
* Active autoimmune disease requiring systemic treatment in past 2 years
* Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis

Primary outcomes:
measure: Overall Response Rate (ORR) by BICR Based on IWG Criteria
timeFrame: Up to approximately 99 months
measure: Percentage of Participants Experiencing at Least One Adverse Event (AE)
timeFrame: Up to 27 months
measure: Percentage of Participants Discontinuing Study Drug Due to AEs
timeFrame: Up to 24 months
Secondary outcomes:
measure: Overall Response Rate (ORR) by BICR Based on Lugano Criteria
timeFrame: Up to approximately 99 months
measure: Overall Response Rate (ORR) Assessed by Investigator Based on IWG Criteria
timeFrame: Up to approximately 99 months
measure: Complete Remission Rate (CRR) by BICR Based on IWG Criteria
timeFrame: Up to approximately 99 months
measure: Complete Remission Rate (CRR) by BICR Based on Lugano Criteria
timeFrame: Up to approximately 99 months
measure: Complete Remission Rate (CRR) Assessed by Investigator Based on IWG Criteria
timeFrame: Up to approximately 99 months
measure: Progression-free Survival (PFS) Based on BICR
timeFrame: Up to approximately 99 months
measure: Progression-free Survival (PFS) Assessed by the Investigator
timeFrame: Up to approximately 99 months
measure: Duration of Response (DOR) Based on BICR
timeFrame: Up to approximately 99 months
measure: Duration of Response (DOR) Assessed by the Investigator
timeFrame: Up to approximately 99 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 99 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Armand P, Zinzani PL, Lee HJ, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von Tresckow B, Shipp MA, Herrera AF, Lin J, Kim E, Chakraborty S, Marinello P, Moskowitz CH. Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma. Blood. 2023 Sep 7;142(10):878-886. doi: 10.1182/blood.2022019386.
citation: Chen R, Zinzani PL, Lee HJ, Armand P, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von Tresckow B, Shipp MA, Lin J, Kim E, Nahar A, Balakumaran A, Moskowitz CH. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019 Oct 3;134(14):1144-1153. doi: 10.1182/blood.2019000324. Epub 2019 Aug 13.
citation: van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.
citation: von Tresckow B, Fanale M, Ardeshna KM, Chen R, Meissner J, Morschhauser F, Moskowitz C, Zinzani PL, Giezek H, Balakumaran A, Vo TT, Raut M, Brice P. Patient-reported outcomes in KEYNOTE-087, a phase 2 study of pembrolizumab in patients with classical Hodgkin lymphoma. Leuk Lymphoma. 2019 Nov;60(11):2705-2711. doi: 10.1080/10428194.2019.1602262. Epub 2019 Apr 23.
citation: Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von Tresckow B, Shipp MA, Zhang Y, Ricart AD, Balakumaran A, Moskowitz CH; KEYNOTE-087. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol. 2017 Jul 1;35(19):2125-2132. doi: 10.1200/JCO.2016.72.1316. Epub 2017 Apr 25.