This study is a multicenter, open-label, randomized clinical trial aimed at exploring the efficacy and safety of three treatment regimens for treatment-naive advanced NSCLC patients with KRAS G12D mutation: GFH375 monotherapy (Cohort 1), GFH375 combined with cetuximab (Cohort 2), and GFH375 combined with pemetrexed (Cohort 3).Every cohort will recruit 30 participants.
Voluntarily agree to participate in this study and sign the written informed consent form.
Male or female, aged 18 to 75 years at the time of signing the informed consent form.
Pathologically (histologically or cytologically) confirmed advanced (Stage IV) or locally advanced non-squamous non-small cell lung cancer that is not amenable to radical surgery or radiotherapy.
Have a written report confirming KRAS G12D mutation positive.
Has had another invasive malignancy that progressed or required treatment within 3 years prior to randomization, except adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, squamous cell carcinoma in situ, superficial bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, or papillary thyroid carcinoma.
Pathologically (histologically or cytologically) confirmed squamous cell lung cancer, adenosquamous carcinoma, neuroendocrine carcinoma (including small cell lung cancer and large cell neuroendocrine carcinoma), or mixed small cell lung cancer.
Known to harbor other targetable driver gene alterations.
Has active or symptomatic brain metastases, leptomeningeal metastases, or spinal cord compression.