PD-(L)1-refractory, Relapsed or Refractory Classical Hodgkin Lymphoma MedDRA version: 20.1 Level: LLT Classification code 10080208 Term: Classical Hodgkin lymphoma System Organ Class: 100000004864
Conditions
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has histologically confirmed diagnosis of classical Hodgkin lymphoma that is FDG-avid, defined as 4-5 on a 5-point scale. 2. Has radiographically measurable disease per the Lugano response criteria, as assessed locally by the investigator, with at least 1 nodal lesion (nonirradiated) that is >1.5 cm in the long axis, regardless of length of the short axis, AND/OR extranodal lesion of >1.0 cm in the long and short axis. 3. Has relapsed (defined as disease progression after most recent therapy) or refractory (defined as failure to achieve CR or PR to most recent therapy) cHL and exhausted all available treatment options with known clinical benefit, including: a) Have failed to achieve a response or progressed after auto-SCT, or Were unable to achieve a CR or PR to salvage chemotherapy, and therefore did not proceed to auto-SCT or were ineligible for auto-SCT due to age/comorbidities as judged by the treating physician. A minimum of 2 lines of prior therapy is required for participants who were ineligible for auto-SCT. b) Have relapsed after treatment with or failed to respond to BV or was ineligible for BV or who discontinued BV due to toxicity. 4. Has progressed on treatment with an anti-PD-(L)1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies (excluding LAG-3-targeted therapies). PD-1 treatment progression is defined by meeting all of the following criteria: a) Received at least 3 months of therapy (with at least 2 doses) of an approved anti-PD-(L)1 mAb b) Documented disease progression after anti-PD-(L)1 treatment, as defined by Lugano classification. c) Progressive disease has been documented within 12 weeks from the last dose of anti-PD-(L)1 mAb as determined by the investigator. If disease progression was confirmed with a second scan, the initial date of disease progression documentation will be considered the date of disease progression. 5. Is male or female, at least 18 years of age, at the time of providing informed consent. 6. If male, agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: - Bendamustine: 90 days - Gemcitabine: 90 days • Refrains from donating sperm PLUS either: • Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR • Uses contraception unless confirmed to be azoospermic 7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Not a WOCBP OR • A WOCBP and: - Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle. The length of time required to continue contraception for each study intervention is as follows: ? MK-4280A: 120 days ? Bendamustine: 180 days ? Gemcitabine: 180 days - Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours (urine) or 72 hours (serum) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if t
Exclusion criteria
Exclusion criteria: 1. Has severe hypersensitivity (Grade =3) to pembrolizumab, favezelimab and/or any of their excipients. 2. History of Grade =3 immune-related adverse event with prior checkpoint inhibitor therapy. 3. 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 before the first dose of study intervention. 4. History of CNS metastases or active CNS involvement. 5. Active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid). 6. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 7. Has an active infection requiring systemic therapy. 8. History of hemophagocytic lymphohistiocytosis. 9. Has an active seizure disorder that is not well controlled. 10. Has clinically significant (ie, active) cardiovascular disease as follows: cerebral vascular accident/stroke (5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease. Participants with a history of GvHD who have been off immunosuppressive therapy for <2 months are excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.To compare MK-4280A to physician’s choice chemotherapy with respect to PFS per Lugano response criteria by BICR. 2.To compare MK-4280A to physician’s choice chemotherapy with respect to OS. ;Secondary Objective: 1.To compare MK-4280A to physician’s choice chemotherapy with respect to OS 2. To evaluate MK-4280A to physician's choice chemotherapy with respect to ORR per Lugano response criteria by BICR. 3.To evaluate MK-4280A and physician’s choice chemotherapy with respect to DOR per Lugano response criteria by BICR. 4.To evaluate the safety and tolerability of MK-4280A. ;Primary end point(s): 1.Progression-Free Survival (PFS) per Lugano Response Criteria as Assessed by Blinded Independent Central Review (BICR) 2.Overall Survival (OS);Timepoint(s) of evaluation of this end point: 1.Up to approximately 43 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall Survival (OS) 2. Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by BICR 3. Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR 4. Number of Participants Who Experienced At Least One Adverse Event (AE) 5. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE);Timepoint(s) of evaluation of this end point: 1. Up to approximately 105 months 2. Up to approximately 25 months 3. Up to approximately 43 months 4. Up to approximately 27 months 5. Up to approximately 24 months | — |
Countries
Australia, Belgium, Brazil, China, Czechia, France, Germany, Israel, Japan, Korea, Republic of, Poland, Spain, Sweden, Turkey, United Kingdom, United States
Outcome results
None listed