Safety and Efficacy of Pembrolizumab (MK-3475) in Children and Young Adults With Classical Hodgkin Lymphoma (MK-3475-667/KEYNOTE-667)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 2

Conditions: Hodgkin Lymphoma

Treatments: Drug: doxorubicin; Drug: vincristine; Radiation: Radiotherapy (RT); Drug: prednisone/prednisolone; Drug: cyclophosphamide; Biological: pembrolizumab; Drug: vinblastine; Drug: bleomycin; Drug: dacarbazine; Drug: etoposide

Study type: Interventional

Funder types: Industry

Identifiers

NCT03407144

2023-504821-38 (Registry Identifier)

MK-3475-667 (Other Identifier)

3475-667

2017-001123-53 (EudraCT Number)

Details and patient eligibility

About

This study will examine the safety and efficacy of pembrolizumab (MK-3475) in combination with chemotherapy in children and young adults with newly diagnosed classical Hodgkin Lymphoma (cHL) who are slow early responders (SERs) to frontline chemotherapy.

Full description

Group 1 will consist of low-risk participants with cHL Stages IA, IB and IIA without bulky disease. Group 2 will consist of high-risk participants with cHL Stages IIEB, IIIEA, IIIEB, IIIB, IVA and IVB.

Enrollment: 340 estimated patients

Sex: All

Ages: 3 to 25 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Group 1: Must have newly diagnosed, pathologically confirmed classical Hodgkin Lymphoma (cHL) at Stages IA, IB and IIA without bulky disease. Group 2: Must have newly diagnosed, pathologically confirmed cHL at Stages IIEB, IIIEA,IIIEB, IIIB, IVA and IVB
• Has measurable disease per investigator assessment.
• Male participants are eligible to participate if they agree to the following during the intervention period: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent or must agree to use contraception per protocol unless confirmed to be azoospermic.
• Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception during the intervention period and for at least 120 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
• Performance status: Lansky Play-Performance Scale ≥50 for children up to 16 years of age OR Karnofsky score ≥50 for participants ≥ 16 years of age
• Has adequate organ function

Exclusion criteria

• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years
• WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
• Baseline left ventricular ejection fraction value <50% or shortening fraction of <27%
• Has received prior therapy with an anti-Programmed Death (PD)-1, anti-Programmed Death-Ligand 1 (PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a MSD pembrolizumab (MK-3475) clinical study
• Has received any prior systemic anti-cancer therapy,including investigational agents for current diagnosis before randomization
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Has a diagnosis of lymphocyte-predominant Hodgkin Lymphoma (HL)
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab
• Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
• Has radiographically detectable central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator at the time of diagnosis
• Has severe hypersensitivity (≥Grade 3) to any study therapies including any excipients
• An active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (non-infectious) 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
• Has a known history of Hepatitis B or known active Hepatitis C virus infection
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
• Participants who have not adequately recovered from major surgery or have ongoing surgical complications

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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340 participants in 2 patient groups

Pembrolizumab + AVD (Group 1)

Experimental group

Description:

After receiving two 4-week cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) induction therapy, SER participants in Group 1 will receive pembrolizumab 2 mg/kg up to a maximum of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) on Day 1 of each 3-week cycle (Q3W) in combination with two cycles of AVD chemotherapy (doxorubicin 25 mg/m\^2, vinblastine 6 mg/m\^2 and dacarbazine 375 mg/m\^2 on Days 1 and 15; cycle frequency every 4 weeks \[Q4W\]). All SERs in Group 1 will receive radiotherapy (RT) after completing AVD chemotherapy.

Treatment:

Drug: bleomycin

Drug: dacarbazine

Drug: vinblastine

Biological: pembrolizumab

Radiation: Radiotherapy (RT)

Drug: doxorubicin

Pembrolizumab + COPDAC-28 (Group 2)

Experimental group

Description:

After receiving two 4-week cycles of OEPA (vincristine, etoposide/etopophos, prednisone/prednisolone and doxorubicin) induction therapy, SER participants in Group 2 will receive pembrolizumab 2 mg/kg up to a maximum of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) Q3W, in combination with 4 cycles of COPDAC-28 chemotherapy (cyclophosphamide 500 mg/m\^2 on Days 1 and 8, vincristine 1.5 mg/m\^2 with maximum single dose 2 mg on Days 1 and 8, prednisone/prednisolone 40 mg/m\^2/day divided in 3 doses on Days 1 to 15, dacarbazine 250 mg/m\^2 on Days 1 to 3; cycle frequency Q4W). SERs in Group 2 will receive RT if they have a positive Positron Emission Tomography (PET) response after completing COPDAC-28 chemotherapy.

Treatment:

Drug: etoposide

Drug: dacarbazine

Biological: pembrolizumab

Drug: cyclophosphamide

Radiation: Radiotherapy (RT)

Drug: prednisone/prednisolone

Drug: vincristine

Drug: doxorubicin