A Study of AK138D1 Alone or in Combination With Ivonescimab in Advanced Non-Small Cell Lung Cancer

This is a multicenter, open-label phase Ib/II study of AK138D1 as monotherapy or in combination with ivonescimab in patients with advanced non-small cell lung cancer. The phase Ib portion is designed to evaluate the safety, tolerability, and preliminary antitumor activity of AK138D1 in combination with ivonescimab. The phase II portion is designed to evaluate the safety and efficacy of AK138D1 as monotherapy or in combination with ivonescimab.

• AK138D1 (Drug): Enrolled subjects will receive intravenous infusion (IV) of AK138D1 according to the dosing regimen specified in their cohort.
• Ivonescimab (Drug): Enrolled subjects will receive intravenous infusion (IV) of Ivonescimab according to the dosing regimen specified in their cohort.
• Carboplatin (Drug): Enrolled subjects will receive intravenous infusion (IV) of Carboplatin according to the dosing regimen specified in their cohort.

Primary outcomes

• Adverse events (AEs) [Up to approximately 2 years]: Incidence and severity of subjects with adverse events
• Objective Response Rate (ORR) [Up to approximately 2 years]: Objective Response Rate (ORR) is the proportion of subjects with complete response (CR) or partial response (PR) , assessed by investigator according to RECIST v1.1.

Secondary outcomes

• Disease Control Rate (DCR) [Up to approximately 2 years]: Disease control rate (DCR) assessed by investigator according to RECIST v1.1.
• Duration of response (DoR) [Up to approximately 2 years]: Duration of response (DoR) assessed by investigator according to RECIST v1.1.
• Time to response (TTR) [Up to approximately 2 years]: Time to response (TTR) is defined as the time to response assessed by investigator according to RECIST v1.1.
• Progression Free Survival (PFS) [Up to approximately 2 years]: Progression Free Survival (PFS) is defined as the time from randomization to the first documented disease progression (per RECIST v1.1) assessed by investigator or death due to any cause, whichever occurs first.
• Overall Survival (OS) [Up to approximately 2 years]: Overall Survival (OS) is defined as the time from randomization to death due to any cause.
• Pharmacokinetics (PK) characteristics [Up to approximately 2 years]: Serum drug concentration profiles at different time points after administration.
• Anti-drug antibodies (ADA) [Up to approximately 2 years]: Number of subjects with detectable anti-drug antibodies (ADA).

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1. The subject must sign the written informed consent form (ICF) voluntarily;
2. At enrollment, aged ≥ 18 to ≤ 75 years, both males and females are eligible;
3. Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
4. Has a life expectancy of ≥ 3 months;
5. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
6. Has Stage IIIB/IIIC or IV non-small cell lung cancer (NSCLC) (American Joint Committee on Cancer \[AJCC\]).
7. Adequate organ function.

Exclusion Criteria:

1. Concomitant participation in another clinical study, unless it is a non-interventional clinical study or the follow-up period of an interventional study;
2. Presence of active central nervous system (CNS) metastases.
3. Live vaccines or attenuated live vaccines administered within 4 weeks prior to the first dose, or planned to be administered during the study; use of inactivated vaccines is allowed;
4. Untreated subjects with active hepatitis B or active hepatitis C;
5. Known active pulmonary tuberculosis (TB); subjects with suspected active TB must undergo appropriate clinical assessment to rule out the presence of active disease;
6. Known active syphilis infection;
7. Subjects with known allergy to any component of any study drug; and with a history of known severe hypersensitivity reactions to other monoclonal antibodies;
8. Other reasons for ineligibility as evaluated by investigator.