China Pharmaceutical Research & Development Center Co., Ltd.

To evaluate the safety and tolerability of a single dose of CRB4101 tablets in healthy adults. Secondary objective: To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of a single dose of CRB4101 tablets in healthy adults. Exploratory objectives: 1. To explore the relationship between the blood concentration of CRB4101 (and its main metabolites, if necessary) and the QTc interval; 2. To explore the metabolism and excretion characteristics of CRB4101 after a single dose (if necessary); 3. To explore the pharmacokinetic characteristics of the main metabolites of CRB4101 (if necessary); 4. The effect of pharmacogenomics on pharmacokinetic characteristics (if necessary).

Subject 1: Patients with locally advanced/metastatic NSCLC who are EGFR mutation-positive Subject 2: Patients with locally advanced/metastatic NSCLC who have EGFR ex20ins Phase Ia Primary objectives: 1. Evaluate the safety and tolerability of NIP142 capsules in subject 1. 2. Explore the DLT and MTD of NIP142 capsules in subject 1. Secondary objectives: 1. Evaluate the PK characteristics of NIP142 capsules and their major metabolites (if data permit) in subject 1. 2. Preliminary evaluation of ORR, DOR, DCR, PFS and OS of NIP142 capsules in subject 1 [only for patients with EGFR ex20ins]. Phase Ib Primary objectives: Evaluate the ORR of NIP142 capsules in subject 2. Secondary objectives 1. Determine the RP2D of NIP142 capsules in subject 2. 2. Evaluate the DOR, DCR, PFS and OS of NIP142 capsules in subject 2. 3. Evaluate the safety of NIP142 capsules in trial subject 2. 4. Based on the population PK analysis method, explore the PK characteristics of NIP142 capsules in trial subject 2 (if data permit).

To evaluate the safety and tolerability of multiple administrations of NIP046 in healthy subjects. Secondary objectives: (1) To evaluate the pharmacokinetic (PK) characteristics of multiple administrations of NIP046 in healthy subjects; (2) Exploratory objectives: To evaluate the biomarkers (target occupancy) of NIP046.