Study of Safety and Efficacy of Pembrolizumab and Chemotherapy in Participants With Newly Diagnosed Classical Hodgkin Lymphoma (cHL) (MK-3475-C11/KEYNOTE-C11)

Merck Sharp & Dohme (MSD)

Status and phase

Completed

Phase 2

Conditions

Classical Hodgkin Lymphoma

Treatments

Drug: Etoposide

Biological: Pembrolizumab

Drug: Doxorubicin

Drug: Dacarbazine

Drug: Bleomycin

Drug: Procarbazine

Drug: Cyclophosphamide

Drug: Prednisone

Drug: Vinblastine

Drug: Vincristine

Study type

Interventional

Funder types

Industry

Identifiers

NCT05008224

3475-C11

MK-3475-C11 (Other Identifier)

2022-501615-14-00 (Registry Identifier)

KEYNOTE-C11 (Other Identifier)

2021-001244-95 (EudraCT Number)

U1111-1281-5347 (Registry Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) monotherapy, followed by chemotherapy, followed by pembrolizumab consolidation. The primary hypothesis of the study is that the complete response (CR) rate at the end of study intervention according to Lugano 2014 response criteria is higher than conventional chemotherapy.

Enrollment

146 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

The main inclusion criteria include, but are not limited to the following:

Has a histologically confirmed diagnosis of Ann Arbor Stage III or IV classical Hodgkin Lymphoma (cHL). Stage I and II participants may be enrolled, but must have at least one National Comprehensive Cancer Network (NCCN) unfavorable risk factor per protocol
Has measurable 2-fluorodeoxyglucose (FDG)-avid disease based on investigator assessment according to Lugano 2014 response criteria
Has not received prior radiation therapy, chemotherapy, immunotherapy, or other systemic therapy for the treatment of cHL before the first dose of study intervention
Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days before the start of study intervention

Exclusion criteria

The main exclusion criteria include, but are not limited to the following:

Has confirmed nodular lymphocyte-predominant Hodgkin Lymphoma (HL)
Has an uncontrolled intercurrent cardiovascular illness
Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 protein (PD-L1), or anti- programmed cell death ligand 2 protein (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
Has received or is expected to receive a live or live-attenuated vaccine within 30 days before the first dose of study intervention
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 or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
Has radiographically detectable central nervous system metastases and/or carcinomatous meningitis
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
Has a history or current evidence of pulmonary fibrosis
Has had an allogenic tissue/solid organ transplant

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Sequential Assignment

Masking

None (Open label)

146 participants in 1 patient group

Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation

Experimental group

Description:

After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan.

Treatment: