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.
12345What 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.
23678Is 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.
234910Eligibility 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.
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Participant Groups
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.
7Treatment groups
Experimental Treatment
Group I: Part B: iNHL-Combination TherapyExperimental Treatment2 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 TherapyExperimental Treatment2 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-MonotherapyExperimental Treatment2 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 TherapyExperimental Treatment2 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+PembrolizumabExperimental Treatment2 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+pembrolizumabExperimental Treatment2 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+pembrolizumabExperimental Treatment2 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 NearbySelect 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
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Who Is Running the Clinical Trial?
Merck Sharp & Dohme LLCLead Sponsor
Merck Sharp & Dohme Corp.Lead Sponsor
References
Pembrolizumab for the treatment of diffuse large B-cell lymphoma. [2020]Introduction: Pembrolizumab is a novel monoclonal antibody that targets the interaction between programmed cell death protein 1 (PD-1) and its ligand (PD-L1). Pembrolizumab has shown significant clinical efficacy in Hodgkin Lymphoma (HL), but results in non Hodgkin Lymphoma (NHL) are mixed. Some NHL subtypes, which share certain genetic features with HL, such as alterations in chromosome 9p24.1 and expression of PD-L1, have shown promising responses in early phase trials. Areas covered: In this review, we provide an overview of pembrolizumab as a compound, and present the available clinical efficacy and safety data in the treatment of diffuse large B cell lymphomas. Expert opinion: Current early phase data suggest that single agent pembrolizumab in NHL demonstrates both efficacy and a favorable safety profile. However, it is anticipated that future treatment strategies will be biomarker-driven and incorporate pembrolizumab into combination therapies with chemotherapy and/or immunotherapy agents.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Pembrolizumab: first global approval. [2021]Pembrolizumab [Keytruda(®) (US)], a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of cancer. Pembrolizumab has received its first global approval for the treatment of advanced, unresectable or metastatic malignant melanoma in the US, for use in patients with disease progression after prior treatment with ipilimumab and, for BRAF V600 mutation-positive patients, a BRAF inhibitor. It is the first anti-PD-1 therapy to receive regulatory approval in the US, and is currently under regulatory review in the EU. This article summarizes the milestones in the development of pembrolizumab leading to this first approval for the treatment of malignant melanoma.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
New developments in the management of advanced melanoma - role of pembrolizumab. [2020]Cancer immunotherapy is now recognized to be fundamental in modern oncology, because immune system recruitment may represent a powerful and innovative strategy in cancer therapy. Pembrolizumab, a highly selective humanized monoclonal antibody directly blocking the interaction between programmed cell death-1 expressed by tumor-associated T-cells and its ligand programmed cell death-L1 present on tumor and stromal cells, was recently approved by US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression upon ipilimumab and BRAF inhibitor. This review will focus on the clinical development and use of pembrolizumab in the clinical practice and in the management of advanced melanoma.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]On December 18, 2015, the FDA granted regular approval to pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) for treatment of patients with unresectable or metastatic melanoma based on results of two randomized, open-label, active-controlled clinical trials. In trial PN006, 834 patients with ipilimumab-naïve metastatic melanoma were randomized (1:1:1) to pembrolizumab 10 mg/kg i.v. every 2 or 3 weeks until disease progression or ipilimumab 3 mg/kg every 3 weeks for up to four doses. In trial PN002, 540 patients with ipilimumab-refractory metastatic melanoma were randomized (1:1:1) to pembrolizumab 2 or 10 mg/kg i.v. every 3 weeks or to investigator's choice of chemotherapy. In trial PN006, patients randomized to pembrolizumab demonstrated a statistically significant improvement in overall survival compared with ipilimumab [every-2-week arm: hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.47-0.83; P < 0.001; every-3-week arm: HR = 0.69; 95% CI, 0.52-0.90; P = 0.004]. In both trials, patients receiving pembrolizumab demonstrated statistically significant improvements in progression-free survival. The most common (≥2%) immune-mediated adverse reactions in a pooled safety analysis were hypothyroidism, pneumonitis, and hyperthyroidism. Key considerations for approval were determination of pembrolizumab dose and interpretation of tumor response-based endpoints using RECIST or immune-related RECIST. Clin Cancer Res; 23(19); 5661-5. ©2017 AACR.
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
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]In this first-in-human study (NCT03564691) in advanced solid tumors, we investigated a novel first-in-class human IgG4 monoclonal antibody targeting the immunoglobulin-like transcript 4 (ILT4) receptor, MK-4830, as monotherapy and in combination with pembrolizumab.
Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. [2023]PD-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer (NK)/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers.