A Clinical Trial of Calderasib (MK-1084) and Durvalumab in People With Non-Small Cell Lung Cancer (MK-1084-015/KANDLELIT-015)

A Phase 3, Randomized, Double-blind, Placebo- and Active-Comparator-Controlled Study of MK-1084 Plus Durvalumab Versus Placebo Plus Durvalumab in Participants With Locally Advanced, Unresected KRAS G12C-Mutant Non-Small Cell Lung Cancer Without Disease Progression Following Definitive Platinum-Based Chemoradiotherapy (KANDLELIT-015)

Researchers are looking for new ways to treat locally advanced non-small cell lung cancer (NSCLC) that is unresected and has a gene mutation called KRAS G12C. Researchers want to learn if calderasib (MK-1084) can be given with durvalumab, an immunotherapy, to treat NSCLC after chemotherapy and radiation therapy.

The goal of this trial is to learn if participants who receive calderasib and durvalumab live longer without the cancer growing or spreading compared to participants who receive placebo and durvalumab.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Calderasib; Biological: Durvalumab; Other: Placebo to MK-1084

• Study Type: Interventional
• Enrollment (Estimated): 310
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@msd.com

Study Locations

• South Korea
  • Taegu-Kwangyokshi
    • Daegu, Taegu-Kwangyokshi, South Korea, 42601
      • Recruiting
      • Keimyung University Dongsan Hospital ( Site 2503)
      • Contact: Study Coordinator; Phone Number: +82532586671
• Taiwan
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital ( Site 2601)
    • Contact: Study Coordinator; Phone Number: +886-6-2353535#3120
• Ukraine
  • Odesa Oblast
    • Odesa, Odesa Oblast, Ukraine, 65025
      • Recruiting
      • Municipal non-profit enterprise'Odesa Regional Clinical Hospital'of Odesa Regional Council ( Site 2011)
      • Contact: Study Coordinator; Phone Number: +380972147211
  • Vinnytsia Oblast
    • Vinnytsia, Vinnytsia Oblast, Ukraine, 21029
      • Recruiting
      • Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council" ( Site 2004)
      • Contact: Study Coordinator; Phone Number: +380432511160
• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Recruiting
      • NHO Revive Research Institute LLC ( Site 0118)
      • Contact: Study Coordinator; Phone Number: 402-484-4900

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Has a histological or cytological diagnosis of locally advanced, unresected Stage II (node-positive) to III non-small cell lung cancer (NSCLC) with predominantly nonsquamous histology.
• Has completed definitive platinum-based concurrent chemoradiotherapy (CCRT) prior to enrollment, without disease progression.
• Has provided a tumor tissue sample for central laboratory testing of Kirsten rat sarcoma G12C (KRAS G12C) status, programmed cell death ligand 1 (PD-L1) status, and biomarker research.
• Tumor tissue sample has a demonstrated presence of KRAS G12C mutation and an evaluable PD-L1 status result.
• If human immunodeficiency virus (HIV)-infected, has well-controlled HIV on antiretroviral therapy (ART).
• If hepatitis B surface antigen (HBsAg)-positive, has undetectable hepatitis B virus (HBV) viral load and has received HBV antiviral therapy.
• If has a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load.
• Has a body weight ≥35 kg.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• Has a diagnosis of small cell lung cancer or mixed tumors with small cell elements.
• Has a gastrointestinal disorder affecting absorption or is unable to swallow orally administered medication.
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease.
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
• Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Has received prior treatment (other than definitive CCRT) for NSCLC.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.
• Has a history of, or has current, (noninfectious) pneumonitis/interstitial lung disease that required/requires steroids.
• Has an active infection requiring systemic therapy.
• Has a history of stem cell/solid organ transplant.
• Has not adequately recovered from major surgery or has ongoing surgical complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Calderasib + Durvalumab; Participants will receive calderasib and durvalumab.	Drug: Calderasib; Tablet for oral administration.; Other Names: MK-1084; Biological: Durvalumab; Solution for intravenous (IV) infusion.; Other Names: IMFINZI®
Active Comparator: Placebo + Durvalumab; Participants will receive placebo to calderasib and durvalumab.	Biological: Durvalumab; Solution for intravenous (IV) infusion.; Other Names: IMFINZI®; Other: Placebo to MK-1084; Placebo to MK-1084.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.	Up to approximately 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 9 years
Number of Participants Who Experience an Adverse Events (AEs)	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE will be presented.	Up to approximately 9 years
Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 9 years
Objective Response Rate (ORR)	ORR is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.	Up to approximately 9 years
Duration of Response (DOR)	For participants who demonstrate confirmed CR or PR per RECIST 1.1 as assessed by BICR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.	Up to approximately 9 years
Distant Metastasis-Free Survival (DMFS)	DMFS is defined as the time from randomization to the first diagnosis of a distant metastasis as assessed by investigator, or death due to any cause, whichever occurs first. Distant metastasis refers to cancer that has spread beyond the original (primary) tumor/regional metastases to distant organs or distant lymph nodes.	Up to approximately 9 years
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) (Items 29 & 30) Combined Score	EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The change from baseline in GHS and QoL combined score will be presented.	Baseline and up to approximately 9 years
Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Combined Score	EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score will be presented.	Baseline and up to approximately 9 years
Change from Baseline in Role Functioning (EORTC QLQ-C30 Items 6 & 7) Combined Score	The EORTC QLQ-C30 is a cancer specific health-related quality of life questionnaire. The role functioning score is based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of Items 6 and 7 and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicate better role functioning. The change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) combined score will be reported.	Baseline and up to approximately 9 years

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Estimated): June 5, 2026
• Primary Completion (Estimated): December 15, 2032
• Study Completion (Estimated): August 17, 2037

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 28, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; durvalumab
• Other Study ID Numbers: 1084-015; 2025-522038-29-00 (Registry Identifier: EU CT); U1111-1321-6971 (Registry Identifier: UTN); MK-1084-015 (Other Identifier: MSD); KANDLELIT-015 (Other Identifier: MSD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No