Favezelimab + Pembrolizumab for Hodgkin Lymphoma

Recruiting at 107 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmune disease, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 18 months

200 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers are looking for a way to treat classical Hodgkin lymphoma (cHL) that is relapsed (the cancer has come back after treatment) or refractory (current treatment has stopped working to slow or stop cancer growth). Researchers want to learn if people who receive coformulated favezelimab/pembrolizumab (MK-4280A) live longer without the cancer getting worse compared to those who receive chemotherapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or other immunosuppressive treatments, you may not be eligible to participate.

What data supports the effectiveness of the drug combination Favezelimab + Pembrolizumab for Hodgkin Lymphoma?

Research shows that Pembrolizumab, part of the drug combination, has a 69% overall response rate in patients with relapsed/refractory classical Hodgkin lymphoma, indicating its effectiveness in improving health outcomes for this condition. ^{1 2 3 4 5}

Is the combination of Favezelimab and Pembrolizumab safe for humans?

Pembrolizumab, used in combination with other treatments, has shown an acceptable safety profile in patients with Hodgkin lymphoma and other conditions. Common side effects include fatigue, nausea, and immune-related reactions like thyroid issues and inflammation of the lungs or liver. In studies, some patients experienced serious side effects, but these were generally manageable. ^{1 6 7 8 9}

What makes the drug combination of Favezelimab and Pembrolizumab unique for treating Hodgkin Lymphoma?

The combination of Favezelimab and Pembrolizumab is unique because it involves two immune checkpoint inhibitors that target different pathways to enhance the body's immune response against Hodgkin Lymphoma. Pembrolizumab targets the PD-1 pathway, which is crucial in Hodgkin Lymphoma, while Favezelimab may target another pathway, potentially offering a novel approach compared to existing treatments. ^{1 5 10 11 12}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with classical Hodgkin Lymphoma that's active despite previous treatments, including anti-PD-(L)1 therapy. They must have a confirmed diagnosis and provide tissue samples. Excluded are those with immunodeficiency, CNS metastases, active autoimmune diseases or infections, recent cancer therapies or surgeries, other malignancies within 3 years, HIV, or past organ transplants.

Inclusion Criteria

My Hodgkin lymphoma is confirmed and shows up on special scans.

My cancer has worsened despite treatment with specific immune therapy.

I can provide a recent (less than 5 years old) tumor sample that hasn't been exposed to radiation.

Exclusion Criteria

I am still recovering from a major surgery.

I have or had lung inflammation that needed steroids.

I have another cancer that is getting worse or was treated in the last 3 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either coformulated favezelimab/pembrolizumab or physician's choice chemotherapy

Up to 18 months

Every 3 weeks for up to 35 infusions or up to 6 cycles of chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 39 months

Treatment Details

Interventions

• Bendamustine
• Favezelimab
• Gemcitabine
• Pembrolizumab

Trial Overview The study tests coformulated favezelimab/pembrolizumab against standard chemotherapy (bendamustine or gemcitabine) in patients whose lymphoma didn't respond to prior treatments. It aims to see if the new drug combo improves survival without disease progression compared to existing chemo options.

Participant Groups

Group I: Favezelimab/Pembrolizumab Experimental Treatment 1 Intervention

Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) by intravenous (IV) infusion on Day 1, then every three weeks (Q3W), for up to 35 infusions.

Group II: Chemotherapy (Bendamustine or Gemcitabine) Active Control 2 Interventions

Participants will receive physician's choice of EITHER bendamustine by IV infusion at a dose between 90 and 120 mg/m\^2 on Day 1 and Day 2 of either a 3- or 4-week cycle for up to 6 cycles OR gemcitabine by IV infusion at a dose between 800 and 1200 mg/m\^2 on Day 1 and Day 8 of a 3-week cycle for up to 6 cycles.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In the KEYNOTE-087 study, pembrolizumab demonstrated a 69% overall response rate in patients with relapsed/refractory classical Hodgkin lymphoma, indicating its efficacy as a treatment option.

Health-related quality of life assessments showed significant improvements in overall health and functional scores among 206 patients at 12 and 24 weeks, suggesting that pembrolizumab not only helps in treating the disease but also enhances patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in KEYNOTE-087, a phase 2 study of pembrolizumab in patients with classical Hodgkin lymphoma. von Tresckow, B., Fanale, M., Ardeshna, KM., et al.[2020]

In a phase 2 trial involving 30 patients with untreated advanced-stage classic Hodgkin lymphoma, nearly two-thirds achieved complete or near-complete metabolic responses after receiving pembrolizumab alone, and all patients achieved complete responses after subsequent AVD chemotherapy, with a 100% overall survival rate at a median follow-up of 33.1 months.

The study found that all patients had genomic alterations in chromosome 9p24.1 and were positive for PD-L1, indicating that even low levels of PD-L1 expression can lead to effective responses to PD-1 blockade, suggesting a broad applicability of this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma. Allen, PB., Lu, X., Chen, Q., et al.[2023]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

In a phase Ib trial (KEYNOTE-028) involving 43 patients with advanced anal carcinoma, pembrolizumab showed a manageable safety profile, with 64% experiencing treatment-related adverse events, but no treatment-related deaths or discontinuations.

Among patients with PD-L1-positive tumors, pembrolizumab achieved a 17% overall response rate and a 58% disease control rate, indicating promising antitumor activity and supporting further research in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ott, PA., Piha-Paul, SA., Munster, P., et al.[2021]

In patients with relapsed and refractory classical Hodgkin's lymphoma who have previously failed treatment with brentuximab vedotin, pembrolizumab significantly improves progression-free survival (PFS) compared to standard of care, with hazard ratios indicating a much lower risk of disease progression.

The study involved a systematic literature review and comparisons of outcomes from pembrolizumab's KEYNOTE-087 trial against an observational study of standard care, confirming that pembrolizumab is a more effective treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. Keeping, S., Wu, E., Chan, K., et al.[2019]

In a study of 30 patients with untreated classic Hodgkin lymphoma, the combination of pembrolizumab with chemotherapy (AVD) demonstrated a 100% overall response rate and a 90% complete response rate, indicating high efficacy.

The treatment was generally safe, with no significant delays in administration; however, some patients experienced serious adverse events, including febrile neutropenia and immune-related effects, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. Lynch, RC., Ujjani, CS., Poh, C., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase 2 trial involving 30 patients with relapsed follicular lymphoma, the combination of pembrolizumab and rituximab showed a promising overall response rate of 67% and a complete response rate of 50%.

The treatment demonstrated a favorable safety profile, with most adverse events being low-grade; however, 20% of patients discontinued due to treatment-related adverse effects, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma. Nastoupil, LJ., Chin, CK., Westin, JR., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant clinical efficacy in treating Hodgkin Lymphoma and promising early results in certain subtypes of Non-Hodgkin Lymphoma, particularly those with genetic similarities to HL.

Current data suggest that pembrolizumab has a favorable safety profile and efficacy as a single agent in treating diffuse large B cell lymphomas, with future strategies likely to focus on biomarker-driven approaches and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. Sheikh, S., Kuruvilla, J.[2020]

Pembrolizumab, an immune checkpoint inhibitor targeting the PD-1 pathway, significantly improves progression-free survival in patients with relapsed or refractory Classical Hodgkin lymphoma (cHL), particularly in those who have undergone autologous stem cell transplant or have chemotherapy-resistant disease.

While there is promising evidence for combining pembrolizumab with chemotherapy to enhance treatment efficacy, further large-scale randomized studies are necessary to confirm these benefits and to develop predictive biomarkers for patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of pembrolizumab for classical Hodgkin lymphoma. Manji, F., Laister, RC., Kuruvilla, J.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in KEYNOTE-087, a phase 2 study of pembrolizumab in patients with classical Hodgkin lymphoma. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

KEYNOTE-013 4-year follow-up of pembrolizumab in classical Hodgkin lymphoma after brentuximab vedotin failure. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. [2020]

12. England pubmed.ncbi.nlm.nih.gov

An evaluation of pembrolizumab for classical Hodgkin lymphoma. [2022]