| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| PD-(L)1-refractory, Relapsed or Refractory Classical Hodgkin Lymphoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Relapsed or Refractory Classical Hodgkin Lymphoma |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10080208 |
| E.1.2 | Term | Classical Hodgkin lymphoma |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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.
|
|
| E.2.2 | Secondary objectives of the trial |
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.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 the serum pregnancy result is positive.
- Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention (MK-4280A) or 180 days after bendamustine or gemcitabine.
- Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy.
8. The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. The participant may also provide consent/assent for FBR. However, the participant may participate in the study without participating in FBR.
9. Is eligible to receive at least one of the protocol-defined chemotherapy regimens in the opinion of the investigator in accordance with local and/or institutional guidelines.
10. Has provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Archival tissue must have been collected <5 years before Screening. Details pertaining to tumor tissue submission can be found in the Laboratory Manual.
11.Has submitted pretrial imaging.
12. An ECOG performance status of 0 to 2 assessed within 7 days before the start of study intervention. Participants with ECOG performance status of 2 will be capped at 20%.
13. Adequate organ function. Specimens must be collected within 7 days before the start of study intervention.
|
|
| E.4 | Principal 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 (<6 months before enrollment), myocardial infarction (<6 months before enrollment), unstable angina, congestive heart failure (NYHA Class III or IV), or cardiac arrhythmia requiring medication.
11. Received prior therapy with a LAG-3-targeted therapy.
12. Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
13. Received prior radiotherapy within 2 weeks of start of study intervention or radiationrelated toxicities requiring corticosteroids.
14. Received a live or live attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
15. Has not adequately recovered from major surgical procedure or has ongoing surgical complications.
16. Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
17. Known additional malignancy that is progressing or has required active treatment within the past 3 years.
18. History of HIV infection. HIV testing is not required unless mandated by local health authority.
19. Concurrent active hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
20. History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
21. Has had an allogeneic hematopoietic stem cell or solid organ transplantation within the last 5 years. Participants who have a transplant >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.
|
|
| E.5 End points |
| E.5.1 | 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) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1. Up to approximately 43 months |
|
| E.5.2 | 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) |
|
| E.5.2.1 | 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 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Biomarkers: PD-L1, LAG-3 IHC; RNAseq, WES, Blood for Genetic Analysis for GWAS and baseline WES |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Brazil |
| China |
| Israel |
| Japan |
| Korea, Republic of |
| United States |
| France |
| Poland |
| Sweden |
| Spain |
| Czechia |
| Germany |
| Belgium |
| Turkey |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 9 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 9 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
