a Study to Evaluate the Safety and Efficacy of D-1553 Combined With IN10018 in KRAS G12C Mutant Solid Tumors

This study includes 2 phases: Phase Ib-Dose Escalation and Phase II-Dose Expansion. Phase Ib-Dose Escalation part will enroll at least 6 subjects to identify the safety and RP2D of D1553 in combination with IN10018 in KRAS G12C mutant solid tumors. Phase II-Dose Expansion part contains 3 cohorts with cohort A to enroll advanced colorectal cancer (CRC) with KRAS G12C mutation, cohort B to enroll advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation, and cohort C to enroll other advanced solid tumors with KRAS G12C mutation. Phase II study is to evaluate the safety and antitumor activities of D-1553 in combination with IN10018 in KRAS G12C mutant solid tumors. The sample size in each cohort is estimated per Simon's 2-stage design. In Cohort A, when Simon's 2-stage study achieved statistical hypothesis, an open-label, randomized study will be conducted for factorial analysis to evaluate the contribution of IN10018 in the combination regimen.

Inclusion criteria

• Men or women aged ≥ 18 years at the time of signing the informed consent form.
• Subjects with pathologically confirmed locally advanced or metastatic solid tumors.
• Confirmed positive KRAS G12C mutation in tumor tissue or other biospecimens (only for phase1b) containing cancer cells or DNA.
• Tumor types in different phases and cohorts: 1) Phase 1b: subjects with locally advanced or metastatic solid tumors who have progressed on or failed in standard therapy, and no standard treatment is available. 2) Phase II Cohort A: subjects with locally advanced or metastatic CRC. 3) Phase II Cohort B: subjects with locally advanced or metastatic NSCLC. 4) Phase 2 Cohort C: subjects with other locally advanced or metastatic solid tumors.
• Has measurable lesions at baseline according to RECIST 1.1 criteria.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone marrow, liver, renal, and coagulation function within 7 days prior to the first dose.

Exclusion criteria

• Prior KRAS G12C inhibitors treatment.
• Have known symptoms of spinal cord compression, instable or symptomatic central nervous system (CNS) metastases, and/or carcinomatous meningitis.
• Have a history of stroke or other serious cerebrovascular diseases within 12 months prior to the first dose.
• Have had interstitial lung disease or any active infection requiring systemic treatment within 14 days prior to the first dose.
• Has a history of severe cardiovascular disease such as acute myocardial infarction, severe/unstable angina, QTc prolongation, or poorly controlled hypertension.
• Haven't recovered from toxicity due to prior antitumor therapy
• Pregnant or lactating women.
• Malignant neoplasms other than study disease within 5 years prior to enrollment.