MK-1084 / Merck (MSD), Otsuka - LARVOL DELTA

MK-1084 for KRAS G12C-mutated advanced colorectal cancer (CRC): Updated findings from KANDLELIT-001 (ESMO Asia 2025) - P1 | "In arm 6, pts with advanced CRC and 0-1 prior systemic therapies received MK-1084 (total daily dose 25-100 mg) plus cetuximab 500 mg/m2 Q2W and mFOLFOX6... Updated data continue to show manageable safety profiles and evidence of antitumor activity for MK-1084–based regimens in pts with advanced, KRAS G12C-mutated CRC. The phase 3 KANDLELIT-012 study is evaluating MK-1084 + cetuximab + mFOLFOX as first-line therapy for KRAS G12C-mut advanced CRC."

Metastases • Colorectal Cancer • Oncology • Solid Tumor • KRAS

KANDLELIT-012: Phase 3 study of MK-1084 (a KRAS G12C inhibitor) plus cetuximab and mFOLFOX6 with or without bevacizumab for KRAS G12C-mutant colorectal cancer. (ASCO-GI 2026) - P3 | "Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Clinical Trial Registration Number: NCT06997497 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

KANDLELIT-014: A Clinical Study of MK-1084 in People With Advanced Solid Tumors (MK-1084-014) (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Pan tumor • Oncology • Solid Tumor • KRAS

A Clinical Study of MK-1084 With Rosuvastatin and Metformin in Healthy People (MK-1084-016) (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed

KEYMAKER-U01 Substudy 01J: A Study of Pembrolizumab Plus MK-1084 in Participants With Non-Small Cell Lung Cancer (NSCLC) With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C Mutations (MK-3475-01J/KEYMAKER-U01J) (clinicaltrials.gov) - P2 | N=130 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

A Study of MK-1084 in Participants With Hepatic Impairment and Healthy Volunteers (MK-1084-017) (clinicaltrials.gov) - P1 | N=58 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

A Clinical Study of MK-1084 With Rosuvastatin and Metformin in Healthy People (MK-1084-016) (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open

A Clinical Study of MK-1084 and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007) (clinicaltrials.gov) - P3 | N=675 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

A Clinical Study of MK-1084 With Rosuvastatin and Metformin in Healthy People (MK-1084-016) (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

A Study of MK-1084 in Participants With Hepatic Impairment and Healthy Volunteers (MK-1084-017) (clinicaltrials.gov) - P1 | N=58 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial • Hepatology

A Study to Evaluate the Effect of Formulation and Food on MK-1084 in Healthy Adult Participants (MK-1084-011) (clinicaltrials.gov) - P1 | N=52 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion

MK-1084 monotherapy in participants (Pts) with KRAS G12C–mutated advanced solid tumors: Activity and safety in the phase I KANDLELIT-001 study (ESMO 2025) - P1 | "Enrollment is ongoing. Table: 926MO CRC NSCLC PDAC HBC Various Total Sample size 53 21 15 8 15 112 ORR 38% (95% CI; 24.8–52.1) 38% (95% CI; 18.1–61.6) 27% (95% CI; 7.8–55.1) 75% (95% CI; 34.9–96.8) 20% (95% CI; 4.3–48.1) 37% (95% CI; 27.7–46.2) DCR 83% (95% CI; 70.2–91.9) 76% (95% CI; 52.8–91.8) 47% (95% CI; 21.3–73.4) 88% (95% CI; 47.3–99.7) 80% (95% CI; 51.9–95.7) 77% (95% CI; 67.9–84.2) CRC, colorectal cancer; HBC, hepatobiliary cancer; NSCLC, non–small cell lung cancer; PDAC, Pancreatic ductal adenocarcinoma."

Clinical • Metastases • Monotherapy • P1 data • Biliary Cancer • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

KANDLELIT-014: A Clinical Study of MK-1084 in People With Advanced Solid Tumors (MK-1084-014) (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

Monotherapy • New P2 trial • Pan tumor • Oncology • Solid Tumor • KRAS

A Clinical Study of MK-1084 and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007) (clinicaltrials.gov) - P3 | N=675 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

A Clinical Study of MK-1084 With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012) (clinicaltrials.gov) - P3 | N=477 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Solid Tumor • KRAS

A Clinical Study of MK-1084 With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012) (clinicaltrials.gov) - P3 | N=477 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jun 2031 ➔ Oct 2030

Trial completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Solid Tumor • KRAS

A Study to Evaluate the Effect of Formulation and Food on MK-1084 in Healthy Adult Participants (MK-1084-011) (clinicaltrials.gov) - P1 | N=52 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed

MK-1084 for KRAS G12C-mutated (mut) metastatic non–small-cell lung cancer (mNSCLC): Results from KANDLELIT-001. (ASCO 2025) - P1 | "Pts with previously untreated nonsquamous mNSCLC received MK-1084 50-200 mg/d + pembro 200 mg, carboplatin, and pemetrexed Q3W in arm 4. In pts with KRAS G12C-mut mNSCLC, MK-1084 shows manageable safety and antitumor activity as monotherapy for previously treated disease and in combination with pembro ± chemo as first-line (1L) therapy. The >90% decrease from baseline in KRAS G12C VAF in ctDNA confirms MK-1084 target engagement. The phase 3 KANDLELIT-004 study is evaluating MK-1084 + pembro as 1L therapy for KRAS G12C-mut mNSCLC with PD-L1 TPS ≥50%."

IO biomarker • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

The KRAS G12C inhibitor MK-1084 for KRAS G12C–mutated advanced colorectal cancer (CRC): Results from KANDLELIT-001. (ASCO 2025) - P1 | "Preliminary data suggest that MK-1084 monotherapy, MK-1084 + cetuximab, and MK-1084 + cetuximab + mFOLFOX6 have manageable safety profiles and show evidence of antitumor activity in pts with advanced, KRAS G12C-mutated CRC. Pts continue to be followed, and enrollment continues."

Metastases • Colorectal Cancer • Dermatitis • Dermatology • Febrile Neutropenia • Immunology • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Study to Evaluate the Effect of Formulation and Food on MK-1084 in Healthy Adult Participants (MK-1084-011) (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open

Research on Novel Treatment Approaches and Scientific Advances From Merck’s Broad and Differentiated Oncology Portfolio and Pipeline to be Presented at ASCO 2025 (Merck (MSD) Press Release) - "New and updated data for MK-1084, an investigational KRAS G12C inhibitor, from the colorectal cancer and non-small cell lung cancer cohorts of the Phase 1 KANDLELIT-001 study will be presented; Zilovertamab vedotin and sacituzumab tirumotecan data to highlight progress in Merck’s pipeline of innovative antibody-drug conjugates; Follow-up data for KEYTRUDA (pembrolizumab) and WELIREG (belzutifan), as well as new and updated analyses for KEYTRUDA in earlier stages of cancer, add to the body of evidence supporting the role of these medicines."

Clinical data • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Melanoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Prostate Cancer • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Von Hippel-Lindau Syndrome

A Clinical Study of MK-1084 With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012) (clinicaltrials.gov) - P3 | N=477 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P3 trial • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Solid Tumor • KRAS

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 Harbo (Gurufocus) - P1 | N=830 | KANDLELIT-001 (NCT05067283) | Sponsor: Merck Sharp & Dohme LLC | "Merck...has announced encouraging results from its Phase 1 KANDLELIT-001 trial involving MK-1084, an investigational KRAS G12C inhibitor....In the colorectal cancer cohort, MK-1084 was tested both as a standalone treatment and in combination with cetuximab and mFOLFOX6 chemotherapy. The overall response rate (ORR) for patients receiving MK-1084 in combination with cetuximab and mFOLFOX6 was particularly impressive, reaching 66% (46-82% CI) for unconfirmed responses. Meanwhile, the NSCLC cohort showed a remarkable 77% (65-86% CI) ORR in patients receiving MK-1084 combined with KEYTRUDA, especially those whose tumors express PD-L1 tumor proportion scores of 1% or higher."

P1 data • Colorectal Cancer

A Clinical Study of MK-1084 in Participants With Renal Impairment (MK-1084-010) (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Renal Disease

A Study to Evaluate the Effect of Formulation and Food on MK-1084 in Healthy Adult Participants (MK-1084-011) (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial