Favezelimab + Pembrolizumab for Lymphoma

Not currently recruiting at 26 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Steroids, Immunosuppressants, others

Disqualifiers: CNS involvement, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new treatments, favezelimab and pembrolizumab (also known as KEYTRUDA), for individuals with certain blood cancers, such as classical Hodgkin lymphoma, diffuse large B-cell lymphoma, and indolent non-Hodgkin lymphoma. The trial aims to determine the safety and effectiveness of these treatments, either together or alone, in managing these cancers. Participants with a tumor measurable by scans and able to provide a tumor sample might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these new treatments.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have received certain anticancer therapies, monoclonal antibodies, or live vaccines recently. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like systemic steroids or have received certain therapies recently. It's best to discuss your specific medications with the trial team.

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 patients with certain types of lymphoma. Studies have found that patients typically tolerate the treatment well, with side effects similar to those of other treatments in this category.

Patients with classical Hodgkin lymphoma (cHL) who had not previously received anti–PD-1 therapies experienced a manageable safety profile with this combination. Side effects were controllable, allowing patients to continue treatment without major issues.

Overall, while side effects can occur, they are often similar to those seen with other treatments in this category and are usually manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining favezelimab and pembrolizumab for treating lymphoma because they target the immune system in innovative ways. Unlike standard treatments, which often focus on directly attacking cancer cells, these drugs enhance the body's immune response. Pembrolizumab is a well-known checkpoint inhibitor that blocks the PD-1 pathway, helping immune cells recognize and attack cancer cells. Favezelimab adds another layer by targeting the LAG-3 protein, a different checkpoint that can dampen immune activity. This dual approach could potentially lead to more robust and effective immune system attacks on lymphoma, offering hope for improved outcomes compared to existing therapies.

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

Research has shown that combining favezelimab with pembrolizumab is promising. In this trial, participants in certain arms will receive this combination, which has led to better response rates and greater tumor size reduction compared to using pembrolizumab alone in previous studies. For individuals with classical Hodgkin lymphoma (cHL) who haven't responded to prior treatments, this combination has demonstrated significant tumor-fighting activity.

Less information exists about favezelimab alone, but it is being tested in this trial for its potential benefits. Participants in other arms will receive pembrolizumab alone, which has already proven effective, with about 69% of cHL patients responding well in earlier trials. These treatments aim to improve outcomes for individuals with hard-to-treat types of lymphoma. ^{2 6 7 8 9}

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 people with certain blood cancers like Hodgkin's lymphoma and B-cell lymphoma. Participants must be relatively healthy (ECOG performance status of 0 or 1), have measurable disease, and can provide a recent tumor biopsy. They shouldn't have severe leftover side effects from past treatments, active infections, CNS involvement, recent vaccines or immunotherapies, HIV/hepatitis B/C infection, pregnancy/breastfeeding plans within the study period, or a history of LAG-3 antibody treatment.

Inclusion Criteria

I can provide a recent or new tumor biopsy for testing.

I have a tumor that can be measured with a scan and is larger than 15mm long or 10mm wide.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have been treated with an anti-LAG-3 antibody before.

My cancer has spread to my brain or spinal cord.

I have had pneumonitis treated with steroids or have it now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Evaluation of dose-limiting toxicities to determine the recommended Phase 2 dose (RP2D)

3 weeks

1 visit (in-person) per cycle

Efficacy Expansion

Participants receive combination or monotherapy treatment for hematologic malignancies

Up to 24 months

1 visit (in-person) every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Favezelimab
• Pembrolizumab

Trial Overview

The trial tests Favezelimab combined with Pembrolizumab in non-randomized groups for some patients and as monotherapy in randomized groups for others with classical Hodgkin lymphoma. It has two phases: an initial phase to ensure safety by looking at dose-limiting toxicities and then an expansion phase to assess effectiveness.

How Is the Trial Designed?

Group I: Part B: iNHL-Combination Therapy Experimental Treatment 2 Interventions

Participants with iNHL receive 200 mg pembrolizumab by IV infusion followed by the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Group II: Part B: cHL-Combination Therapy Experimental Treatment 2 Interventions

Participants with cHL receive 200 mg pembrolizumab by IV infusion followed by the recommended Phase 2 dose (RP2D) of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Group III: Part B: Randomized cHL-Monotherapy Experimental Treatment 2 Interventions

Participants with cHL receive either pembrolizumab by IV infusion or the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to approximately 2 years).

Group IV: Part B: DLBCL-Combination Therapy Experimental Treatment 2 Interventions

Participants with DLBCL receive 200 mg pembrolizumab by IV infusion followed by the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Group V: Part A: Favezelimab Dose C+Pembrolizumab Experimental Treatment 2 Interventions

Participants receive 200 mg pembrolizumab by IV infusion followed by favezelimab Dose C by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Group VI: Part A: Favezelimab Dose B+pembrolizumab Experimental Treatment 2 Interventions

Participants receive 200 mg pembrolizumab by IV infusion followed by favezelimab Dose B by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Group VII: Part A: Favezelimab Dose A+pembrolizumab Experimental Treatment 2 Interventions

Participants receive 200 mg pembrolizumab by intravenous (IV) infusion followed by favezelimab Dose A by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

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

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. 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, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., 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 II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

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]

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]

The first-in-human study of MK-4830, a novel IgG4 monoclonal antibody targeting the ILT4 receptor, showed it was well tolerated with no dose-limiting toxicities among 84 patients with advanced solid tumors.

In combination with pembrolizumab, MK-4830 demonstrated promising antitumor activity, with 11 out of 34 patients achieving objective responses, including some who had previously progressed on other therapies, suggesting enhanced effectiveness in certain tumor microenvironments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Class Anti-immunoglobulin-like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors. Siu, LL., Wang, D., Hilton, J., et al.[2023]

In a study of 59 patients with relapsed/refractory extranodal natural killer/T-cell lymphoma treated with pembrolizumab, the overall response rate was 40.7%, with 28.8% achieving a complete response, indicating its potential efficacy as a salvage therapy.

While pembrolizumab showed modest effectiveness, it was associated with some grade 3 or 4 adverse events in 20.3% of patients, with neutropenia being the most common, suggesting that while it can be beneficial, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. Lee, JY., Kwon, JH., Hur, JY., 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 is a monoclonal antibody that blocks the PD-1/PD-L1 interaction, which is crucial for preventing the immune system from attacking tumors, making it a key player in cancer immunotherapy.

It has been approved by the FDA for treating patients with advanced melanoma who have not responded to previous treatments, highlighting its efficacy in managing difficult cases of this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. Improta, G., Leone, I., Donia, M., et al.[2020]

Citations

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

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

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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.

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ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7056

A phase 1/2 study of favezelimab in combination with ...

Favezelimab + pembrolizumab continued to demonstrate manageable safety and antitumor activity in pts with heavily pretreated anti–PD-1–refractory cHL.

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msdclinicaltrials.com

msdclinicaltrials.com/trial/nct03598608/

Study to Evaluate the Safety and Efficacy of a Combination of ...

This study will also evaluate the safety and efficacy of pembrolizumab or favezelimab administered as monotherapy in participants with cHL using a 1:1 ...

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ashpublications.org

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Favezelimab in Combination with Pembrolizumab in Patients ...

In the safety lead-in, patients received pembrolizumab 200 mg IV Q3W and favezelimab at a starting dose of 200 mg that was escalated to 800 ...

7.

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.

8.

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 safety profile of the fixed-dose combination was consistent with that observed for favezelimab and pembrolizumab in previously reported ...

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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 ...