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 Stable Metastatic Colorectal Cancer

RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the Phase 3 KEYFORM-007 trial evaluating the investigational fixed-dose combination of favezelimab, Merck’s anti-LAG-3 antibody, and pembrolizumab (KEYTRUDA®), Merck’s anti-PD-1 therapy, did not meet its primary endpoint of overall survival (OS) for the treatment of patients with previously treated PD-L1 positive microsatellite stable (MSS) metastatic colorectal cancer (mCRC). At the final pre-specified analysis, the favezelimab and pembrolizumab fixed-dose combination did not demonstrate an improvement in OS compared to standard of care (regorafenib or TAS-102 [trifluridine and tipiracil hydrochloride]). The safety profile of the fixed-dose combination was consistent with that observed for favezelimab and pembrolizumab in previously reported studies, with no new safety signals observed.

A full evaluation of the data is ongoing and Merck will work with investigators to share the results with the scientific community.

“Metastatic colorectal cancer continues to be a challenging disease to treat, especially for the majority of patients who have microsatellite stable disease, which has had limited response to immunotherapies,” said Dr. M. Catherine Pietanza, vice president, global clinical development, Merck Research Laboratories. “We are grateful to the patients and investigators for their participation in this study, and we will continue to advance our clinical development program to evaluate KEYTRUDA-based combinations and novel candidates for patients with colorectal cancer in need of new options.”

In the U.S., KEYTRUDA is approved for the treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer as determined by an FDA-approved test. KEYTRUDA is not approved for the treatment of MSS mCRC.

The favezelimab and pembrolizumab fixed-dose combination is also being evaluated in certain hematologic malignancies and multiple solid tumor types. Ongoing studies include KEYFORM-008, a Phase 3 study evaluating the fixed-dose combination in patients with relapsed or refractory classical Hodgkin lymphoma whose disease has progressed following prior anti-PD-1 therapy.

About KEYFORM-007

KEYFORM-007 is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT05064059) evaluating the fixed-dose combination of favezelimab and pembrolizumab (MK-4280A) versus standard of care, regorafenib or TAS-102 (trifluridine and tipiracil), for the treatment of patients with PD-L1 positive MSS mCRC who were previously treated with standard therapies. The primary endpoint is OS, and key secondary endpoints include progression-free survival, objective response rate, duration of response, safety and quality of life. The trial enrolled 441 patients who were randomized (1:1) to receive:

• Favezelimab/pembrolizumab fixed-dose combination (favezelimab 800 mg and pembrolizumab 200 mg intravenously [IV]) on day 1, then every three weeks (Q3W) for 35 cycles, or
• Investigator’s choice of regorafenib orally once daily on days 1-12 of each 28-day cycle or TAS-102 orally twice daily on days 1-5 and days 8-12 of each 28-day cycle.

About colorectal cancer

Colorectal cancer can be referred to as colon cancer or rectal cancer, depending on where the cancer starts. Colorectal cancer often begins with growths on the inner lining of the colon or rectum called polyps, which can change into cancer over time. Colorectal cancer is the third most commonly diagnosed cancer and the second most common cause of cancer-related death worldwide. It is estimated there were nearly 1.9 million patients diagnosed with colorectal cancer and more than 900,000 patient deaths from the disease globally in 2022. In the United States, it is estimated that there will be approximately 107,000 patients diagnosed with colon cancer and approximately 46,000 patients diagnosed with rectal cancer, resulting in more than 53,000 deaths from colorectal cancer in 2024. The five-year relative survival rates in the U.S. for metastatic colon cancer and rectal cancer (stage IV) are estimated to be 13% and 18%, respectively.

About favezelimab

Favezelimab (MK-4280) is an investigational anti-lymphocyte activation gene-3 (LAG-3) antibody. LAG-3 is a cell surface immunomodulatory receptor expressed on various immune cells that down-regulates T cell proliferation and activation. Favezelimab aims to restore T cell effector function by preventing LAG-3 from binding to its primary ligand, major histocompatibility complex (MHC) class II molecules. The fixed-dose combination of favezelimab and pembrolizumab (MK-4280A) is being evaluated across multiple solid tumor types and in patients with relapsed or refractory classical Hodgkin lymphoma whose disease has progressed following prior anti-PD-1 therapy.

About KEYTRUDA® (pembrolizumab) injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.

See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (

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