Studieoverzicht

Study name: 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 (Krascendo 2)

Histology NSCLC, only non-squamous
Tumor stage Stage III - IV
NCT Id NCT06793215
Host / recruiting site 1 Amphia Enrollment Recruiting
Therapy line First line (1L)
PD-L1 expression Negative: <1%Low: 1 - 49%High: ≥50%
Design

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).

Intervention

DRUG: Divarasib

Divarasib will be administered orally QD

DRUG: Pembrolizumab

Pembrolizumab will be administered via IV infusion Q3W

DRUG: Pemetrexed

Pemetrexed will be administered via IV infusion Q3W

DRUG: Carboplatin

Carboplatin will be administered via IV infusion Q3W

DRUG: Cisplatin

Cisplatin will be administered via IV infusion Q3W

Key outcome parameters
  • Progression-Free Survival (PFS)

  • Overall Survival (OS)

Key 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
Key exclusion criteria

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
Contact information