A Study of HS-10241 Combined With Almonertinib Versus Platinum-based Chemotherapy in Treatment of Advanced NSCLC With MET Amplification After Failure of EGFR-TKI Therapy

1. Treatment with any of the following:

1. Previous or current treatment with drugs targeting the c-MET/HGF pathway.

2. Previous or under treatment with pemetrexed and platinum.

3. Any cytotoxic chemotherapy, investigational agents, antitumor traditional Chinese Medicine and any other anticancer drugs for the treatment of advanced NSCLC within 14 days before the date of randomization; or requiring treatment with these drugs during the study.

4. Any antitumor monoclonal antibody therapy within 28 days before the date of randomization.

5. Local radiotherapy within 2 weeks of the date of randomization; receiving radiation to \> 30% of the bone marrow or with a wide field of radiation within 4 weeks before the date of randomization.

6. Spinal cord compression or brain metastases (except for that being asymptomatic and stable for at least 4 weeks, not requiring steroids for at least 2 weeks prior to start of study treatment and with no obvious edema around the tumor focus by imaging examination).

7. Currently receiving drugs known to prolong QT interval or may cause torsade de pointe; or requiring treatment with these drugs during the study.

2. Any unresolved toxicities from prior therapy greater than Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0 with the exception of alopecia or neurotoxicity.

3. History of other primary malignancies.

4. Inadequate bone marrow reserve or organ function, as demonstrated by any of the following laboratory values:

1. Absolute neutrophil count (ANC) \<1.5×109 / L

2. Platelet count \<90×109 / L

3. Hemoglobin \<90 g/L

4. Total bilirubin (TBL) \> 1.5 × ULN or \> 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases.

5. One or both of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) \> 2.5 × upper limit of normal (ULN) or \> 5 × ULN in the presence of liver metastases.

6. Creatinine \> 1.5 × ULN concurrent with creatinine clearance \< 50 mL/min; confirmation of creatinine clearance is only required when creatinine is \> 1.5 × ULN.

7. International normalized ratio (INR) \> 1.5, and partially activated prothrombin time (APTT) \> 1.5 × ULN.

8. Serum albumin (ALB) \< 28 g/L

5. Any of the following cardiac criteria:

1. Resting corrected QT interval (QTc) \> 470 ms obtained from electrocardiogram (ECG), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF).

2. Left ventricular ejection fraction (LVEF) ≤ 50%.

6. Severe, uncontrolled or active cardiovascular diseases.

7. Diabetes ketoacidosis or hyperglycemia hypertonic occurring within 6 months before the date of randomization, or the glycosylated hemoglobin value ≥ 7.5% in the screening period.

8. Severe or poorly controlled hypertension.

9. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Grade B or more severe cirrhosis.

10. Other moderate or severe lung diseases that may interfere with the detection or treatment of drug-related pulmonary toxicity or may seriously affect respiratory function.

11. Women who are breastfeeding or pregnant or planned to be pregnant during the study period.

12. History of hypersensitivity to any active or inactive ingredient of HS-10241/Almonertinib/ cisplatin/carboplatin/pemetrexed or to drugs with a similar chemical structure or class to HS-10241/Almonertinib/cisplatin/carboplatin/pemetrexed.

13. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

14. Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.

What this study is about