Non-Small Cell Lung Cancer
Conditions
Brief summary
The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of single-agent divarasib or combined with other anti-cancer therapies in participants with previously untreated, advanced or metastatic non-small cell lung cancer (NSCLC).
Interventions
DRUGDivarasib
Participants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
DRUGPembrolizumab
Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.
DRUGCarboplatin
Participants will receive IV carboplatin Q3W for four 21-day cycles.
DRUGCisplatin
Participants will receive IV cisplatin Q3W for four 21-day cycles.
DRUGPemetrexed
Participants will receive IV pemetrexed Q3W.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Cohorts B, C, D, and a subset of Cohort A follow non-randomized allocation; other subsets of Cohort A are randomized.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmation of Biomarker eligibility * Pre-treatment tumor tissue along with an associated pathology report is required for all participants enrolled on study. Representative tumor specimens must be in formalin-fixed, paraffin embedded (FFPE) blocks (preferred) or 15 unstained, freshly cut, serial slides. Although 15 slides are required, if only 10 slides are available, the participant may be eligible for the study following consultation with the Sponsor. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * Histologically or cytologically documented locally advanced unresectable or metastatic NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy * No prior systemic treatment for advanced unresectable or metastatic NSCLC * Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Additionally, for participants in cohort D, measurable brain metastases defined as at least 5 millimeters and twice the slice thickness, but less than 20 mm, that is asymptomatic and does not require local therapy at the time of enrollment.
Exclusion criteria
* Known concomitant second oncogenic driver with available targeted treatment * Squamous cell histology NSCLC * Symptomatic, untreated, or actively progressing CNS metastases (Cohorts A, B, and C) * Prior treatment with a KRAS G12C inhibitor * Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only) * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, active tuberculosis, significant cardiovascular disease within 3 months prior to initiation of study treatment * History of malignancy other than NSCLC within 5 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate more \>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 * Uncontrolled tumor related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia * Co-morbid condition that is an absolute contraindication to treatment with corticosteroids * Inability or unwillingness to take prophylactic treatments such as corticosteroids, anti-emetics, folic acid, or vitamin B12 supplementation. * Participants with brain metastases for whom complete surgical resections is clinically appropriate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants with Adverse Events (AEs) | Baseline until 60 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately 5 years) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Approximately 5 years | The percentage of participants who experience a complete response or partial response, as determined by the investigator, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
| Duration of Response (DOR) | Approximately 5 years | The time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 |
| Progression Free Survival (PFS) | Approximately 5 years | The time from randomization, or date of first treatment for participants enrolled prior to the expansion stage, to the first occurrence of disease progression or death from any cause during the study (whichever occurs first), as determined by the investigator according to RECIST v1.1 |
| Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Side Effects as Assessed Through the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Approximately 5 years | — |
| Change from Baseline in Symptomatic Side Effects, as Assessed Through use of the PRO-CTCAE | Baseline up to approximately 5 years | — |
| Percentage of Participants Reporting "Frequent" or "Almost Constant" Diarrhea During the First Three Cycles of Treatment According to the PRO-CTCAE Criteria | Approximately 5 years | — |
| Percentage of Participants Reporting "Severe" or "Very Severe" Nausea or Vomiting During the First Three Cycles of Treatment According to the PRO-CTCAE | Approximately 5 years | — |
| Frequency of Participant's Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the Single-item European Organisation for Research and Treatment of Cancer (EORTC) Item List 46 (IL46) | Approximately 5 years | — |
| Plasma or CSF Concentration of Divarasib at Specified Timepoints | Approximately 5 years | Optional CSF samples may be collected at the time of disease progression or at any time during the study for participants who have provided written consent and if collection of CSF sample is deemed clinically feasible. Matched optional plasma samples may be drawn at the same time. |
| Identification of Divarasib Recommended Dose | Approximately 5 years | The recommended dose will be based upon the totality of safety, activity, and PK data. |
| Central Nervous System (CNS) Response | Approximately 5 years | Defined as the percentage of participants who experience a complete response or partial response in the brain, as determined by the investigator according to modified RECIST |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Israel, Italy, Japan, Netherlands, Poland, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
CONTACTReference Study ID Number: BO44426 https://forpatients.roche.com/
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed