DNA x FAK

This is a phase 1b, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics and efficacy of JMKX001899 in combination with IN10018 or in combination with chemotherapy or in combination with IN10018 and chemotherapy in subjects with locally advanced or metastatic NSCLC with KRAS G12C mutation.

The purpose of this clinical trial is to evaluate the safety and tolerability of avutometinib and defactinib and to determine the preliminary antitumour activity of avutometinib and defactinib administered at the recommended Phase 2 dose (RP2D). In the Phase 1b of this study parallel biomarker defined arms will be opened, initially in the relapsed GMB setting, enrolling 12 patients onto each arm. These patients will be treated with avutometinib and defactinib double therapy. Avutometinib will be administered orally at 3.2mg twice a week (e.g., on Monday / Thursday or Tuesday / Friday) with or without a meal. The total weekly dose of avutometinib is 6.4mg. Defactinib will be administered orally, at 200mg, twice a day within 30 min after a meal. The total daily dose of defactinib is 400mg.
Once a treatment in any biomarker arm has met the "GO" decision (≥3 successes/12 patients) for relapsed GBM in Phase 1b, that arm can progress to Phase 2. The primary objective of Phase 2 is to determine the antitumour activity of investigational agents administered at the RP2D in patients with molecularly defined malignant brain tumours.

Ib期-剂量确证阶段：旨在一线广泛期小细胞肺癌（ES-SCLC）受试者中评估IN10018联合抗PD-1/ L1单抗和化疗（铂类和依托泊苷）的安全性、药代动力学（PK）参数和确定II期推荐剂量（RP2D）；II期-剂量扩展阶段：进一步评估IN10018联合抗PD-1/L1单抗和化疗（铂类和依托泊苷）对比抗PD-1/L1单抗联合化疗（铂类和依托泊苷）在一线ES-SCLC受试者中的抗肿瘤疗效和安全性。