New Phase 3 data evaluating sacituzumab tirumotecan (sac-TMT), an investigational TROP2-directed antibody-drug conjugate, in previously treated locally recurrent or metastatic triple-negative breast cancer

First presentation of Phase 2b three-year follow-up data evaluating mRNA-4157 (V940), an investigational individualized neoantigen therapy, in combination with KEYTRUDA (pembrolizumab) in patients with high-risk stage III/IV melanoma following complete resection

RAHWAY, N.J.--(BUSINESS WIRE)--$MRK #MRK--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that new data for four approved oncology medicines and four pipeline candidates in more than 25 types of cancer will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago from May 31-June 4. New data being shared at the meeting showcase the company's continued progress to advance clinical research for Merck's broad portfolio and diverse pipeline of investigational candidates.

"At ASCO, the breadth of data across multiple types of cancer and stages of disease underscores our efforts to drive innovations that have potential to shape the future of oncology," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "This year's ASCO is also particularly meaningful as we approach 10 years since KEYTRUDA was first approved in the U.S. Reflecting back, it is remarkable to see just how much the oncology treatment landscape has transformed, thanks to the significant contributions from patients, researchers and physicians around the world."

For KEYTRUDA, key presentations include updated and long-term follow-up data in certain advanced gastrointestinal cancers and advanced melanoma, as well as new quality of life and patient-reported outcomes data in metastatic bladder and earlier stage non-small cell lung cancer.

Key data for KEYTRUDA to be presented at ASCO 2024:

• Three-year follow-up data from the Phase 3 KEYNOTE-966 study evaluating KEYTRUDA plus chemotherapy versus chemotherapy alone for patients with advanced biliary tract cancer (BTC) (Abstract #4093; Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary Poster Session).
• Longer-term follow-up results from the Phase 3 KEYNOTE-859 study evaluating KEYTRUDA plus chemotherapy versus chemotherapy alone for advanced human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction cancer (Abstract #4045; Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary Poster Session).
• Patient-reported outcomes (PROs) from the Phase 3 KEYNOTE-A39/EV-302 trial evaluating KEYTRUDA plus enfortumab vedotin versus chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC) (Abstract #4502; Genitourinary Cancer—Kidney and Bladder Oral Abstract Session).¹
• Health-related quality of life (HRQoL) data from the Phase 3 KEYNOTE-671 study evaluating perioperative KEYTRUDA (neoadjuvant KEYTRUDA plus chemotherapy followed by resection and adjuvant KEYTRUDA as a single agent) versus pre-operative chemotherapy for resectable stage II, IIIA or IIIB non-small cell lung cancer (NSCLC) (Abstract #8012; Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers Rapid Oral Abstract Session).
• Updated efficacy and safety data from both cohorts of the Phase 2 KEYNOTE-224 study evaluating KEYTRUDA monotherapy in patients with sorafenib-treated and treatment- naïve advanced hepatocellular carcinoma (HCC) (Abstract #4100; Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary Poster Session).
• Long-term data from the Phase 2 KEYNOTE-629 study evaluating KEYTRUDA for recurrent/metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation (Abstract #9554; Melanoma/Skin Cancers Poster Session).

As Merck continues to build its broad oncology portfolio, the company will also present data at ASCO from its diverse pipeline of investigational candidates, many being evaluated in combination with KEYTRUDA. This includes mRNA-4157 (V940), an investigational individualized neoantigen therapy (INT) being developed in collaboration with Moderna, in combination with KEYTRUDA; vibostolimab/pembrolizumab, an investigational coformulation of vibostolimab, an anti-TIGIT therapy, and KEYTRUDA; sacituzumab tirumotecan (sac-TMT; formerly MK-2870/SKB264), an investigational anti-TROP2 antibody-drug conjugate (ADC) being developed in collaboration with Kelun-Biotech; and patritumab deruxtecan (HER3-DXd), a HER3-directed ADC being developed in collaboration with Daiichi Sankyo.

Key data from Merck's pipeline to be presented at ASCO 2024:

• First presentation of three-year follow-up data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial evaluating mRNA-4157 (V940) in combination with KEYTRUDA as adjuvant treatment for resected high-risk melanoma (Abstract #LBA9512; Melanoma/Skin Cancers Rapid Oral Abstract Session).²
• Data from a Phase 3 study conducted in China, independently led by Kelun-Biotech, evaluating sac-TMT versus chemotherapy as treatment for previously treated locally recurrent or metastatic TNBC (Abstract #104; Next-Generation Antibody–Drug Conjugates: The Revolution Continues Clinical Science Symposium Session).³
• First-time data from a Phase 2 study conducted in China, independently led by Kelun-Biotech, evaluating sac-TMT in combination with KL-A167 (a PD-L1 antibody) as first-line treatment for advanced NSCLC (Abstract #8502; Lung Cancer—Non-Small Cell Metastatic Oral Abstract Session).³
• Data from cohort B1 of the Phase 2 KeyVibe-005 study evaluating vibostolimab/pembrolizumab in patients with previously treated advanced mismatch repair-deficient (dMMR) endometrial cancer (Abstract #5502; Gynecologic Cancer Oral Abstract Session).

Merck investor event
Merck will hold an Oncology Investor Event to coincide with the 2024 ASCO Annual Meeting on Monday, June 3, 2024, 6 p.m. CT, at which senior management will provide an update on the company's oncology strategy and program. The event will take place in Chicago, Ill., and will be accessible via webcast. Investors, analysts, members of the media and the general public are invited to listen to a webcast of the presentation via this weblink.

Details on abstracts listed above and additional key abstracts for Merck

¹ In collaboration with Pfizer and Astellas
² Led by Moderna
³ Independent study led by Kelun-Biotech
⁴ Sponsored by Georgetown University, in collaboration with BioXcel Therapeutics, Inc.
⁵ In collaboration with Eisai

About Merck's early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with more than 25 ongoing registrational studies across multiple types of cancer.

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.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.

Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

• stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
• metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.

Urothelial Carcinoma
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:

• who are not eligible for any platinum-containing chemotherapy, or
• who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

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.

Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.

Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract carcinoma (BTC).

Endometrial Carcinoma
KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) as determined by an FDA-approved test or not MSI-H, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) 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 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis
KEYTRUDA as a Single Agent
KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA With Axitinib
KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment.

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