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Merck Announces MK-1084, an Investigational KRAS G12C Inhibitor, Shows Antitumor Activity in Phase 1 Trial of Patients With Advanced Colorectal Cancer and Non-Small Cell Lung Cancer Whose Tumors Harbor KRAS G12C Mutations

RAHWAY, N.J.--(BUSINESS WIRE) May 30, 2025 -- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today safety and efficacy results from the open-label Phase 1 KANDLELIT-001 study, a clinical trial evaluating MK-1084, an investigational next-generation KRAS G12C inhibitor, alone and in combination with other therapies in certain patients with KRAS G12C-mutant solid tumors, including advanced colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). In patients with advanced KRAS G12C-mutated CRC and NSCLC, a manageable safety profile and antitumor activity were observed with MK-1084 either as a monotherapy or in the combinations.

“We are encouraged by the promising early data from the KANDLELIT-001 study and look forward to further researching the potential for MK-1084, as monotherapy or in combinations, including with KEYTRUDA in certain settings in patients with KRAS mutations, which are among the most prevalent mutations in cancer,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “We are committed to evaluating the potential for innovative approaches to help even more patients with cancer and these results further demonstrate the potential of our robust and differentiated pipeline.”

In CRC, the study assessed MK-1084 as monotherapy, as well as in combination with cetuximab with or without chemotherapy (oxaliplatin and leucovorin plus 5-fluorouracil [mFOLFOX6]). For efficacy, the study evaluated overall response rate (ORR), with the following results for efficacy evaluable patients:

MK-1084 Monotherapy

Previously treated CRC1

N=53

MK-1084 + Cetuximab

Previously treated CRC2

N=39

MK-1084 + Cetuximab + mFOLFOX63

Metastatic CRC with 0-1 lines of prior therapy

N=29

Confirmed response, % (95% CI)

ORR

38% (25-52)

46% (30-63)

38% (21-58)

Unconfirmed response, % (95% CI)

ORR

43% (30-58)

56% (40-72)

66% (46-82)

1 Median follow-up for all advanced CRC patients in these arms = 23.2 months (range, 0.2-37.7)

2 Median follow-up for all patients in this treatment arm = 9.2 months (range, 0.5-15.6)

3 Median follow-up for all patients in this treatment arm = 4.6 months (range, 0.1 -9.5)

In NSCLC, MK-1084 was evaluated as monotherapy, as well as in combination with KEYTRUDA with or without chemotherapy (carboplatin and pemetrexed), with the following ORR results for efficacy evaluable patients:

MK-1084 Monotherapy

Previously treated NSCLC4

N=21

MK-1084 + KEYTRUDA

Untreated metastatic NSCLC whose tumors express PD-L1 tumor proportion score [TPS] ≥1%5

N=69

MK-1084 + KEYTRUDA+ Chemotherapy (carboplatin and pemetrexed)

Untreated metastatic NSCLC6

N =40

ORR, % (95% CI)

38% (18-62)

77% (65-86)

53% (36-69)

4 Median follow-up for all NSCLC patients in these arms = 18.9 months (range, 0.0-36.4)

5 Median follow-up for all patients in this treatment arm = 12.1 months (range, 0.8-33.4)

6 Median follow-up for all patients in this treatment arm = 8.5 months (range, 0.5-16.5)

Across all arms of the KANDLELIT-001 study, MK-1084 had a manageable safety profile. Treatment-related adverse events (TRAEs) occurred in 58% (n=71) of patients in the MK-1084 monotherapy arm, 94% (n=68) of patients in the MK-1084 and KEYTRUDA arm, 93% (n=39) of patients in the MK-1084 in combination with KEYTRUDA and chemotherapy arm, 95% (n=39) of patients in the MK-1084 and cetuximab arm and 97% (n=32) of patients in the MK-1084 with cetuximab and mFOLFOX6 arm.

These KANDLELIT-001 CRC and NSCLC data are being presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #3508 and #8605, respectively).

In addition to KANDLELIT-001, MK-1084 will be investigated in the Phase 3 KANDLELIT-012 study, which is investigating MK-1084 in combination with cetuximab and mFOLFOX6 for the first-line treatment of certain patients with locally advanced unresectable or metastatic CRC who have KRAS G12C-mutated tumors and the Phase 3 KANDLELIT-004 study, which is investigating MK-1084 in combination with KEYTRUDA for the first-line treatment of certain patients with metastatic NSCLC who have KRAS G12C-mutated tumors and express PD-L1 (TPS ≥50%).

MK-1084 is being developed under a collaboration and license agreement with Taiho Pharmaceutical Co. Ltd and Astex Pharmaceuticals (UK), a wholly owned subsidiary of Otsuka Pharmaceutical Co., Ltd.

About KANDLELIT-001

KANDLELIT-001 is a Phase 1, open-label multicenter clinical trial (Clinical Trials.gov, NCT05067283) designed to assess safety, tolerability, pharmacokinetics and efficacy of MK-1084 as monotherapy and in combination with other therapies in patients with KRAS G12C mutated advanced solid tumors. The primary endpoints of the trial were safety and tolerability, as assessed by number of patients who experienced a dose-limiting toxicity, adverse events and treatment discontinuations. Secondary endpoints include objective response rate (ORR) and duration of response.

Merck’s focus on cancer

Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology/.

About Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2024 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Source: Merck & Co., Inc.

Posted: May 2025

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