A Study of HS-20117 Combined With Aumolertinib in Participants With Advanced Non-Squamous Non-Small Cell Lung Cancer

This is a multicenter Phase Ib/III clinical study evaluating the safety, efficacy, pharmacokinetics (PK), and immunogenicity of HS-20117 in combination with aumolertinib in subjects with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). The study is divided into two phases, Phase Ib, a dose expansion study and Phase III, a confirmatory study. In the dose expansion phase (Phase Ib), HS-20117 will first be studied in combination with the standard dose of aumolertinib, to assess the efficacy, safety, tolerability, PK profile, and immunogenicity of HS-20117 in combination with aumolertinib in the target population, as well as to determine the recommended Phase III dose (RP3D). Following confirmation of the safety and efficacy of HS-20117 in combination with aumolertinib and RP3D in Phase Ib, a randomized, active-controlled, open-label, multicenter Phase III study will be initiated to assess the efficacy and safety of HS-20117 in combination with aumolertinib versus aumolertinib in the target population in the confirmatory study phase.

Inclusion criteria

• Males or females aged 18 - 75 years (inclusive).
• Participants with newly diagnosed histologically or cytologically confirmed, locally advanced or metastatic EGFR-sensitive mutated NSCLC (stage IIIB/IIIC/IV) that is treatment naive and not amenable to curative therapy including surgical resection or chemoradiation.
• Agree to provide fresh or archival tumor tissue.
• At least one target lesion per the RECIST v1.1.
• ECOG performance status of 0-1.
• Minimum life expectancy > 12 weeks.
• Males or Females should be using adequate contraceptive measures throughout the study.
• Females must not be pregnant at screening or have evidence of non-childbearing potential.
• Have signed Informed Consent Form.

Exclusion criteria

• Received or are receiving the following treatments:

• Previous or current treatment with MET targeted therapy or EGFR targeted antibodies or antibody-drug conjugates (ADC).
• Traditional Chinese medicine indicated for tumors, major surgery or other local therapy within washout period to the first dose of study drug.
• Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
• Other investigational non-anti-tumor drugs, strong CYP3A4 inhibitors, strong inducers, drugs that are sensitive substrates of BCRP or P-gp, or drugs that prolong the QT interval within the washout period.
• Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy.
• History of other primary malignancies.
• Untreated, or active central nervous system metastases.
• Inadequate bone marrow reserve or organ functions.
• Severe, uncontrolled or active cardiovascular disorders.
• Severe or uncontrolled systemic diseases.
• Severe bleeding symptoms or bleeding tendencies.
• Severe arteriovenous thrombosis occurred.
• Serious or active infection.
• Active infectious diseases.
• Interstitial lung disease (ILD).
• Serious neurological or mental disorders.
• History of hypersensitivity to any component of HS-20117 and Aumolertinib or their similar drugs.
• Female subjects who are pregnant, lactating, or planning to become pregnant or breastfeed during the study period or within 6 months after the last dose of the study drug.
• Subjects with a history of severe allergic reactions or those who have experienced severe infusion reactions
• Participants with any condition that compromises the safety of the participant or interferes with the assessment of the study, as judged by the investigator.