A Study Comparing Divarasib plus Pembrolizumab with Standard Treatment (Pembrolizumab plus Chemotherapy) in People with Untreated Non-Small Cell Lung Cancer with a Change in a Gene Called KRAS G12C that Has Spread
Descrizione riassuntiva dello studio
Non-small cell lung cancer is the most common form of lung cancer. It typically develops in the tissues lining the lungs and can spread to nearby lymph nodes and other organs. The standard first treatment for non-small cell lung cancer that has spread includes a drug that helps the body's immune system attack cancer cells (an immunotherapy). An immunotherapy, such as Pembrolizumab, is usually given along with platinum-based chemotherapy. About 1 in 10 people with non-small cell lung cancer has a specific change (mutation) in the KRAS gene, known as a KRAS-G12C mutation. This change causes cancer cells to grow uncontrollably. Combining an immunotherapy with a treatment that targets this mutation may work better than the current standard treatment for this type of mutation. This study investigates a combination of Divarasib with Pembrolizumab. It is being developed as a treatment option for untreated non-small cell lung cancer that has spread. Divarasib is a targeted therapy that may work well in non-small cell lung cancer with a KRAS-G12C mutation. It is still a drug in the testing phase. This means that it has not yet been approved by the Swissmedic regulatory authority for use alone or in combination with Pembrolizumab for the treatment of non-small cell lung cancer. The goal of this study is to compare the effects of Divarasib with Pembrolizumab to the standard first treatment (Pembrolizumab plus chemotherapy) in people with non-small cell lung cancer and KRAS-G12C mutation that has spread.
(BASEC)
Intervento studiato
Participants will undergo a pre-screening to determine if they are eligible for the study. Pre-screenings will take place one month before treatment begins. All participants in this study will be randomly assigned (like flipping a coin) to one of two groups and will then receive:
● Divarasib, taken daily as tablets (to swallow) plus Pembrolizumab as an infusion into a vein every 3 weeks OR
● Pembrolizumab plus platinum-based chemotherapy as an infusion into a vein every 3 weeks.
The likelihood of being assigned to either group is equal. This study is an open-label study. This means that all parties involved, including participants and study teams, will know who is receiving which study treatment.
During this study, the investigator will examine participants every 3 weeks. The investigator will assess the effectiveness of the treatment and check for any side effects in the participants. Participants will be treated until their disease worsens or until any adverse effects become intolerable. A follow-up is scheduled one month after the completion of the study treatment, during which the investigator will check the health status of the participants. The investigator will continue to monitor the health status of the participants every 3 months until the end of the study through visits, phone calls, or by reviewing their medical records, as long as the person agrees. Participation in the study may last more than 5 years in total, depending on when the person starts the study. Participants have the right to withdraw from the study treatment at any time and stop participating in the study if they wish.
(BASEC)
Malattie studiate
Non-small cell lung cancer
(BASEC)
Individuals aged 18 years or older who have not previously been treated for non-small cell lung cancer that has spread may participate in the study if they cannot be treated with surgery, chemotherapy, or radiation therapy with curative intent. The lung cancer must also have a change in the KRAS gene referred to as 'G12C'. (BASEC)
Criteri di esclusione
Individuals may not be able to participate if they have a type of non-small cell lung cancer that begins in a specific cell type (squamous cells), if the cancer has spread to the brain or spinal cord and is causing symptoms, or if the cancer has other changes in specific genes for which specific treatments are available. Pregnant and breastfeeding individuals are not allowed to participate. (BASEC)
Luogo dello studio
Basilea, Chur, Ginevra, Altro
(BASEC)
Baden
(BASEC)
Sponsor
Roche Pharma (Schweiz) AG
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Clinical Trials
+41 61 715 44 85
switzerland.clinical-research@clutterroche.comRoche Pharma (Schweiz) AG
(BASEC)
Informazioni generali
Hoffmann-La Roche
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione d'etica svizzera nord-ovest/centrale EKNZ
(BASEC)
Data di approvazione del comitato etico
18.09.2025
(BASEC)
ID di studio ICTRP
NCT06793215 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
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 (BASEC)
Titolo accademico
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 (ICTRP)
Titolo pubblico
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 (ICTRP)
Malattie studiate
Non-Small Cell Lung CancerKRAS G12C Lung Cancer (ICTRP)
Intervento studiato
Drug: DivarasibDrug: PembrolizumabDrug: PemetrexedDrug: CarboplatinDrug: Cisplatin (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Criteri di inclusione/esclusione
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 (ICTRP)
non disponibile
Endpoint primari e secondari
Progression-Free Survival (PFS);Overall Survival (OS) (ICTRP)
Change from Baseline on the EORTC QLQ-C30 and QLQ-LC13 Functional and Global Health Status Score/Quality of Life Score (GHS/QoL);Objective Response;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;Change from Baseline on the EORTC Quality of Life Questionnaire (QLQ-C30) Dyspnea Item and Physical Functioning Scale;Duration of Response (DOR);Percentage of Participants with Adverse Events (AEs);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);Change from Baseline in the Severity of Selected Symptomatic Treatment Toxicities as Assessed Through use of the NCI PRO-CTCAE;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) (ICTRP)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
Chugai Pharmaceutical (ICTRP)
Contatti aggiuntivi
Clinical TrialsReference Study ID Number: CO45042 https://forpatients.roche.com/, global-roche-genentech-trials@gene.com, 888-662-6728 (U.S. and Canada), Hoffmann-La Roche (ICTRP)
ID secondari
CO45042 (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT06793215 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile