Non-small Cell Lung Cancer
Conditions
Brief summary
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.
Interventions
DRUGCalderasib
Tablet for oral administration.
BIOLOGICALDurvalumab
Solution for intravenous (IV) infusion.
OTHERPlacebo to MK-1084
Placebo to MK-1084.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 6 years | PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 9 years | OS is defined as the time from randomization to death due to any cause. |
| Number of Participants Who Experience an Adverse Events (AEs) | Up to approximately 9 years | 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. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 9 years | 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. |
| Objective Response Rate (ORR) | Up to approximately 9 years | 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. |
| Duration of Response (DOR) | Up to approximately 9 years | 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. |
| Distant Metastasis-Free Survival (DMFS) | Up to approximately 9 years | 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. |
| 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 | Baseline and up to approximately 9 years | 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. |
| Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Combined Score | Baseline and up to approximately 9 years | 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. |
| Change from Baseline in Role Functioning (EORTC QLQ-C30 Items 6 & 7) Combined Score | Baseline and up to approximately 9 years | 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. |
Contacts
STUDY_DIRECTORMedical Director
Merck Sharpe & Dohme LLC
Outcome results
None listed