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

Calderasib (MK-1084), alone or in combination, for KRAS G12C-mutant metastatic non-small cell lung cancer (mNSCLC) (ESMO 2026) - No abstract available

Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Calderasib Monotherapy in Various KRAS G12C–Mutated Advanced Solid Tumors: Results from the Phase 1 KANDLELIT-001 Study (ESMO 2026) - No abstract available

Metastases • Monotherapy • P1 data • Oncology • Solid Tumor • KRAS

Theoretical study of KRAS G12C secondary mutations influencing inhibitor resistance. (PubMed, Biophys Physicobiol) - "In this study, we investigated the impact of secondary mutations (Y96D, Y96S, G13D, and Q99L) on the binding efficacy of sotorasib, adagrasib, and the next-generation inhibitor (MK-1084) using molecular dynamics simulations, binding free energy calculations, and dynamic protein-ligand interaction analysis. Our analyses revealed that Y96 mutations directly disrupt inhibitor binding, conferring high resistance to all three inhibitors, whereas G13D and Q99L indirectly alter the binding environment by influencing other residues, resulting in variable resistance profiles. This study provides detailed molecular insights into resistance mechanisms to support the rational design of more robust KRAS G12C-targeted therapies."

Journal • Oncology • KRAS

Updated results for MK-1084 + pembrolizumab in KRAS G12C-mutated (mut) metastatic non-small cell lung cancer (mNSCLC) enrolled in KANDLELIT-001 (ELCC 2026) - P1 | "Pts in arm 4 had untreated nonsquamous mNSCLC and received MK-1084 50-200 mg/d + pembro 200 mg, carboplatin, and pemetrexed Q3W. Legal entity responsible for the study Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Funding Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA."

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

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=140 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jan 2033 ➔ May 2032 | Trial primary completion date: Jan 2033 ➔ Nov 2029

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • KRAS

KEYMAKER-U01F: Umbrella Study of Novel Therapies in Previously Treated Advanced/Metastatic Nonsquamous KRAS G12C-Mutant NSCLC (IASLC-WCLC 2026) - P1/2 | "The phase 1b/2 KEYMAKER-U01 substudy F (NCT07286149) will evaluate calderasib in combination with novel therapies, including the HER3-directed antibody-drug conjugate patritumab deruxtecan (HER3-DXd; MK-1022), the TROP2-directed antibody-drug conjugate sacituzumab tirumotecan (sac-TMT; MK-2870), and cetuximab in previously treated advanced or metastatic nonsquamous KRAS G12C-mutant NSCLC. Secondary endpoints include DOR and PFS per RECIST v1.1 by BICR and pharmacokinetic parameters including area under the curve, maximum plasma concentration, and minimum observed concentration. The study is currently enrolling at an anticipated 61 global sites."

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

Calderasib (MK-1084) for KRAS G12C-mutated (mut) advanced colorectal cancer (CRC): Results from KANDLELIT-001 (ESMO-GI 2026) - P1 | "Cal + cetuximab + mFOLFOX6 is being evaluated in 1L KRAS G12C-mutant CRC in the phase 3 KANDLELIT-012 study. Table: 6RO a Pts with ≥1 cal dose ≥7 wk before data cutoff. b Pts with confirmed CR or PR."

Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

Phase 3 Study of Adjuvant Subcutaneous MK-3475A Plus Calderasib or Placebo in Resected Stage IIA-IIIB (N2), KRAS G12Cm NSCLC (IASLC-WCLC 2026) - P3 | "MK-3475A is pembrolizumab with berahyaluronidase alfa (MK-5180), a variant of human hyaluronidase developed and manufactured by Alteogen Inc (Daejeon, South Korea) for subcutaneous (SC) administration. The phase 3 KANDLELIT-013 study (NCT07431827) evaluates adjuvant calderasib in combination with pembrolizumab SC in participants with completely resected, stage IIA-IIIB (N2), KRAS G12C-mutated NSCLC following receipt of neoadjuvant pembrolizumab plus chemotherapy or adjuvant chemotherapy...Secondary endpoints include OS, distant metastasis-free survival per investigator, lung cancer-specific survival, patient reported outcomes, and safety. Enrollment is projected to start in April 2026 at 210 global sites."

Clinical • IO biomarker • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • KRAS • PD-L1

Nursing Management of KRAS G12C Inhibitor Toxicities in Thoracic Malignancy: A Canadian Perspective (IASLC-WCLC 2026) - "Unlike cell-surface receptor targeting-tyrosine kinase inhibitors (TKIs), such as osimertinib and alectinib, which are familiar to thoracic oncology nurses, KRAS G12C inhibitors act upon an intracellular downstream signaling pathway...While first-in-class inhibitors sotorasib and adagrasib are approved, next-generation agents including divarasib, olomorasib, and calderasib are demonstrating more favourable safety profiles in ongoing trials...As KRAS G12C inhibitors expand beyond NSCLC to broader solid tumour indications, proactive, evidence-informed, and standardized nursing management is essential to optimizing patient outcomes and ensuring equitable access to precision oncology care globally. This requires that nurses be equipped with the education and clinical tools for informed, evidence-based symptom management across geographically diverse healthcare systems."

Hepatology • Interstitial Lung Disease • Liver Failure • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Thoracic Cancer • 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

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

From KRASG12D to pan-KRAS inhibitors – a journey enabled by synthetic innovation and structure-based drug design (ACS-Fall 2026) - "We previously disclosed Calderasib (MK-1084), an orally bioavailable, low-dose, covalent KRASG12C inhibitor now in phase III clinical trials...Utilizing high-throughput experimentation (HTE), we further expanded the design of warheads suitable for targeting pan-KRAS inhibition. To deepen our understanding of KRAS pharmacology, we advanced a KRASG12D inhibitor and two pan-KRAS inhibitors into efficacy models, demonstrating robust tumor growth inhibition and establishing their utility as in-vivo tool compounds."

KRAS

A Study of Calderasib (MK-1084) in Participants With Hepatic Impairment and Healthy Volunteers (MK-1084-017) (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Completed | N=58 ➔ 32

Enrollment change • Trial completion • Hepatology

A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F) (clinicaltrials.gov) - P1/2 | N=140 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial primary completion date: Aug 2031 ➔ Aug 2029

Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

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

KANDLELIT-014: A Clinical Study of Calderasib (MK-1084) in People With Advanced Solid Tumors (MK-1084-014) (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Merck Sharp & Dohme LLC

Monotherapy • Pan tumor • Trial initiation date • 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 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

Monotherapy • New P2 trial • Pan tumor • Oncology • 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 | 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

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 primary completion date: Aug 2029 ➔ Mar 2029

Trial primary completion date • 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 | 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 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 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 Calderasib (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 | N=218 ➔ 675

Enrollment change • Trial initiation date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

A clinical trial of MK-1084 and durvalumab in people with non-small cell lung cancer (MK-1084-015) (clinicaltrialsregister.eu) - P2/3 | N=27 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2/3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1