Favezelimab + Pembrolizumab for Hodgkin Lymphoma

Not currently recruiting at 131 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for classical Hodgkin lymphoma (cHL) that has returned after treatment or stopped responding to current therapies. Researchers aim to determine if a combination of two drugs, favezelimab and pembrolizumab, can help patients live longer without their cancer worsening compared to traditional chemotherapy. Favezelimab and pembrolizumab form a new potential drug combination under testing. The trial targets individuals whose cHL has recurred or stopped responding and who have exhausted all other available treatments. Participants will receive either the experimental drug combination or chemotherapy, based on group assignment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining favezelimab and pembrolizumab is generally safe for individuals with classical Hodgkin lymphoma that has returned or stopped responding to treatment. Previous studies found that this treatment combination effectively combats cancer and has manageable side effects. The safety results align with earlier findings, indicating that most individuals tolerate it well. However, responses can vary among individuals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Hodgkin lymphoma?

Unlike the standard chemotherapy options for Hodgkin Lymphoma, which typically include drugs like bendamustine or gemcitabine, the combination of favezelimab and pembrolizumab works by targeting the immune system. Favezelimab is a novel immunotherapy agent that, when combined with pembrolizumab, aims to boost the body's immune response against cancer cells. Researchers are excited because this combination has the potential to offer a more effective and less toxic alternative to traditional chemotherapy, possibly leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for Hodgkin lymphoma?

Research has shown that using favezelimab with pembrolizumab, which participants in this trial may receive, holds promise for treating classical Hodgkin lymphoma that hasn't improved with other treatments. Studies have found that this combination leads to better results and a greater reduction in tumor size compared to using pembrolizumab alone. This combination works well for patients whose cancer doesn't respond to anti-PD-1 treatments, a type of immunotherapy. Early research suggests that favezelimab and pembrolizumab together can help stop the cancer from worsening and are generally safe for patients. Meanwhile, another treatment arm in this trial involves chemotherapy with either bendamustine or gemcitabine, serving as an active comparator. ^{1 2 4 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/bloodadvances/article/9/19/4987/546200/Estimating-efficacy-of-favezelimab-plus

Estimating efficacy of favezelimab plus pembrolizumab ... Favezelimab plus pembrolizumab had a higher response rate and greater reduction in tumor burden vs pembrolizumab alone. Results suggest ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40668662/

Estimating efficacy of favezelimab plus pembrolizumab ... Favezelimab plus pembrolizumab had promising efficacy in anti-programmed cell death protein 1 (PD-1)-refractory classical Hodgkin lymphoma in MK-4280-003; ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03598608

NCT03598608 | Study to Evaluate the Safety and Efficacy ... This study will evaluate the safety and efficacy of favezelimab (MK-4280) in combination with pembrolizumab (MK-3475) using a non-randomized study design.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7055

A phase 1/2 study of favezelimab in combination with ... Favezelimab plus pembrolizumab continued to demonstrate sustained antitumor activity and manageable safety in pts with anti–PD-1–naive R/R cHL.

5. merck.com merck.com/news/merck-provides-update-on-phase-3-keyform-007-trial-evaluating-investigational-fixed-dose-combination-of-favezelimab-and-pembrolizumab-for-patients-with-previously-treated-pd-l1-positive-microsatellite/

Merck Provides Update on Phase 3 KEYFORM-007 Trial ... The Phase 3 KEYFORM-007 trial evaluating the investigational fixed-dose combination of favezelimab, Merck's anti-LAG-3 antibody, and pembrolizumab (KEYTRUDA)

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10431364/

UPDATED RESULTS FROM AN OPEN-LABEL ... Summary/Conclusion: The combination of favezelimab plus pembrolizumab continued to demonstrate antitumor activity and manageable safety in pts with R/R cHL ...