Favezelimab + Pembrolizumab for Lymphoma

Recruiting in Palo Alto (17 mi)

+25 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Merck Sharp & Dohme LLC

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study will evaluate the safety and efficacy of favezelimab (MK-4280) in combination with pembrolizumab (MK-3475) using a non-randomized study design in participants with the following hematological malignancies: * classical Hodgkin lymphoma (cHL) * diffuse large B-cell lymphoma (DLBCL) * indolent non-Hodgkin lymphoma (iNHL) This study will also evaluate the safety and efficacy of pembrolizumab or favezelimab administered as monotherapy in participants with cHL using a 1:1 randomized study design. The study will have 2 phases: a safety lead-in and an efficacy expansion phase. The recommended Phase 2 dose (RP2D) will be determined in the safety lead-in phase by evaluating dose-limiting toxicities. There is no primary hypothesis for this study.

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.

What data supports the idea that Favezelimab + Pembrolizumab for Lymphoma is an effective treatment?

The available research shows that Pembrolizumab, one of the drugs in the combination, has shown promising results in certain types of lymphoma, particularly those with specific genetic features similar to Hodgkin Lymphoma. While the results for non-Hodgkin Lymphoma are mixed, some subtypes have responded well in early trials. This suggests that Pembrolizumab, when used in combination with other treatments like Favezelimab, could be effective for certain lymphoma patients. However, more research is needed to confirm its effectiveness in broader lymphoma cases. ^{1 2 3 4 5}

What safety data is available for Favezelimab + Pembrolizumab treatment?

Pembrolizumab (Keytruda) has been evaluated in various clinical trials and has received FDA approval for the treatment of metastatic melanoma. Common adverse reactions include fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions can include pneumonitis, colitis, hepatitis, hypophysitis, thyroid disorders, and rare cases of type 1 diabetes mellitus. Safety data from trials indicate that pembrolizumab is associated with immune-related adverse events, which are important considerations for its use in cancer treatment. ^{2 3 6 7 8}

Is the drug Favezelimab + Pembrolizumab a promising treatment for lymphoma?

Yes, the drug Pembrolizumab, which is part of the Favezelimab + Pembrolizumab combination, has shown promising results in treating various cancers, including lymphoma. It has been effective in different types of cancer and has received approval for treating advanced melanoma, indicating its potential as a promising treatment. ^{2 3 4 9 10}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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 another cancer besides skin or early cervical cancer, and it's getting worse or needs treatment.

Treatment Details

Interventions

• Favezelimab (Monoclonal Antibodies)
• Pembrolizumab (Monoclonal Antibodies)

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.

Participant Groups

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).

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Jewish General Hospital ( Site 0105) Montreal, Canada

Texas Oncology-Austin Midtown ( Site 8002) Austin, TX

Fox Chase Cancer Center ( Site 0019) Philadelphia, PA

University of California San Francisco ( Site 0023) San Francisco, CA

More Trial Locations

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4096

Patients Recruited

5,232,000+

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2287

Patients Recruited

4,582,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

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]

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, 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Pembrolizumab: first global approval. [2021]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

New developments in the management of advanced melanoma - role of pembrolizumab. [2020]

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

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

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

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

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

9. United States 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. [2023]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. [2023]