A Phase II Study of AK146D1 in Combination With AK112 in Advanced Non-Small Cell Lung Cancer

A Phase II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antitumor Efficacy of AK146D1 in Combination With AK112 or Other Anticancer Therapies in Patients With Advanced Non-Small Cell Lung Cancer

This is a phase II clinical study evaluating the safety, tolerability, pharmacokinetics and antitumor efficacy of AK146D1 in combination with AK112 or other anticancer therapies in patients with advanced Non-Small Cell Lung Cancer.

Inclusion Criteria:

1. Be able to understand and voluntarily sign the written informed consent form.
2. Aged of ≥ 18 years and ≤75 years.
3. ECOG PS 0 or 1.
4. The expected lifespan is ≥3 months.
5. Patients with histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-small cell lung cancer (NSCLC) who are not eligible for curative surgical resection and cannot receive definitive concurrent or sequential chemoradiotherapy.
6. At least one measurable non-brain lesion according to RECIST v1.1.
7. Have sufficient organ function.
8. Females subjects must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception.

Exclusion Criteria:

1. NSCLC mixed with a component of small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma.
2. Having other active malignancies within 3 years.
3. Currently participating in another interventional clinical study.
4. Presence of active metastases to the central nervous system. For patients with asymptomatic brain metastasis or stable symptoms after treatment can be included.
5. Having received any treatment targeting Trop2 or Nectin4.
6. Prior chemotherapy or antibody-drug conjugate (ADC) therapy targeting topoisomerase I inhibitors.
7. Receipt of systemic anti-tumor therapy (including chemotherapy, immunotherapy, biological agents, etc.) within 4 weeks (or 5 half-lives of the drug, whichever is longer) prior to the first dose.
8. Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 6.0 grade 1 or lower.
9. Subjects with clinically significant cardiovascular or cerebrovascular diseases or risks.
10. Subjects with active autoimmune diseases requiring systemic treatment within 2 years.
11. Receipt of systemic anti-infective therapy within 2 weeks prior to the first dose.
12. Known to be positive for HIV and other infections.
13. Previous history of severe hypersensitivity reactions.
14. Live attenuated vaccines were received within 4 weeks.
15. Subjects with a history of mental illness and incapacitated or limited capacity.
16. Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.