A Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Participants With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lu

Brief Summary
The purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or cisplatin, for the first-line treatment of adult participants with KRAS G12C-mutated, advanced or metastatic non squamous non-small cell lung cancer (NSCLC).
Brief Title
A Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Participants With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer
Central Contacts
Central Contact Role
Contact
Central Contact Phone
888-662-6728 (U.S. and Canada)
Central Contact Email
global-roche-genentech-trials@gene.com
Completion Date
Completion Date Type
Estimated
Conditions
Non-Small Cell Lung Cancer
KRAS G12C Lung Cancer
Eligibility Criteria
Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed diagnosis of advanced or metastatic non squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
* Measurable disease, as defined by RECIST v1.1
* No prior systemic treatment for advanced or metastatic NSCLC
* Documentation of the presence of a KRAS G12C mutation
* Documentation of known PD-L1 expression status in tumor tissue
* Availability of a representative tumor specimen
* Adequate end-organ function
* Eligible to receive a platinum-based chemotherapy regimen

Exclusion Criteria Related to NSCLC:

* Known concomitant second oncogenic driver with available targeted treatment
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>=2 weeks prior to randomization
* History of leptomeningeal disease
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once a month or more frequently)

Exclusion Criteria Related to Current or Prior Treatments:

* Any anti-cancer systemic therapy, including hormonal therapy, within 21 days prior to randomization, or is expected to require any other form of antineoplastic therapy while in the study
* Radiation therapy including palliative RT to bone metastases within 2 weeks prior to randomization and RT to the lung \>30Gy within 6 months prior to randomization
* Prior treatment with KRAS G12C inhibitors or pan-KRAS/RAS inhibitors
* Treatment with systemic immunosuppressive or immunostimulatory medications, including CD137 agonists and immune checkpoint inhibitors
* Current treatment with medications that are well known to prolong the QT interval
* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to randomization
* Prior allogeneic stem cell or solid organ transplantation

Exclusion Criteria Related to General Health:

* History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival \[OS\] rate \>90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
* Individuals with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal surgery including gastric resection, a history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) or any active bowel inflammation (including diverticulitis), malabsorption syndrome, conditions that would interfere with enteral absorption
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography scan
* Significant cardiovascular disease within 3 months prior to screening
Inclusion Criteria
Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed diagnosis of advanced or metastatic non squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
* Measurable disease, as defined by RECIST v1.1
* No prior systemic treatment for advanced or metastatic NSCLC
* Documentation of the presence of a KRAS G12C mutation
* Documentation of known PD-L1 expression status in tumor tissue
* Availability of a representative tumor specimen
* Adequate end-organ function
* Eligible to receive a platinum-based chemotherapy regimen

Gender
All
Gender Based
false
Keywords
Advanced Non-Small Cell Lung Cancer
KRAS G12 Lung Cancer
Advanced Lung Cancer
Metastatic lung cancer
Divarasib
KRAS G12C Inhibitor
KRAS G12C Positive
KRAS Mutation
KRAS G12C Mutation
Lung Cancer Mutation
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06793215
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
CO45042
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase III, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Patients With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer
Primary Outcomes
Outcome Description
PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by blinded independent central review (BICR) according to RECIST v1.1, or death from any cause (whichever occurs first)
Outcome Measure
Progression-Free Survival (PFS)
Outcome Time Frame
Up to approximately 5 years
Outcome Description
OS is defined as the time from randomization to death from any cause
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
Up to approximately 5 years
Secondary Outcomes
Outcome Description
Objective response is defined as complete response (CR) or partial response (PR) on two consecutive occasions \>=4 weeks apart, as determined by BICR according to RECIST v1.1
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Objective Response
Outcome Time Frame
Baseline up to Cycle 5 Day 1 (each cycle is 21 days)
Outcome Measure
Change from Baseline on the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Supplemental Lung Cancer Module (EORTC QLQ-LC13) Cough Scale
Outcome Time Frame
Baseline up to Cycle 5 Day 1 (each cycle is 21 days)
Outcome Measure
Change from Baseline on the EORTC Quality of Life Questionnaire (QLQ-C30) Dyspnea Item and Physical Functioning Scale
Outcome Description
DOR is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by BICR according to RECIST v1.1, or death from any cause (whichever occurs first)
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Duration of Response (DOR)
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Percentage of Participants with Adverse Events (AEs)
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Change from Baseline in the Severity of Selected Symptomatic Treatment Toxicities as Assessed Through use of the NCI PRO-CTCAE
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Frequency of Participants' Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the single-item EORTC Item List (IL46)
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Change from Baseline on the EORTC QLQ-C30 and QLQ-LC13 Functional and Global Health Status Score/Quality of Life Score (GHS/QoL)
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Cancer Related - Please Specify
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
LUNG NEOPLASMS
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
PEMBROLIZUMAB
PEMETREXED
CARBOPLATIN
CISPLATIN
GUANINE
HYPOXANTHINES
PURINONES
PURINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
GLUTAMATES
AMINO ACIDS, ACIDIC
AMINO ACIDS
AMINO ACIDS, PEPTIDES, AND PROTEINS
AMINO ACIDS, DICARBOXYLIC
COORDINATION COMPLEXES
ORGANIC CHEMICALS
CHLORINE COMPOUNDS
INORGANIC CHEMICALS
NITROGEN COMPOUNDS
PLATINUM COMPOUNDS