Phase II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of ALK201 for Injection in Combination With Ivonescimab Injection in sqNSCLC Participants.

This is an open-label, multicenter, Phase II clinical study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of ALK201 for Injection combined with Ivonescimab Injection in adult patients with locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC) who are FGFR2b-positive, EGFR mutation-negative, and ALK-negative. The study consists of two parts: Part A (dose escalation) and Part B (dose optimization).

Part A Dose Escalation Stage: This stage includes three dose levels. Eligible patients with locally advanced or metastatic sqNSCLC who have failed standard therapy will be enrolled to complete DLT assessment.

Part B Dose Optimization Stage: This stage comprises two cohorts, enrolling eligible patients with locally advanced or metastatic sqNSCLC satisfying the respective cohort criteria:

Primary cohort: PD-L1 expression ≥1% Exploratory cohort : PD-L1 expression <1%

Inclusion criteria

• The subject fully understands and agrees to comply with all study procedures, and voluntarily signs the pre-screening informed consent form and main study informed consent form.
• Aged ≥18 years and ≤75 years at the time of informed consent signature, with no gender restriction.
• Expected overall survival ≥3 months.
• At least one measurable lesion per RECIST Version 1.1. Lesions previously treated with radiotherapy or other local therapies may serve as target lesions if radiological evidence of disease progression in such lesions is confirmed.
• Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
• Subjects must have adequate organ function, and have not received blood transfusion or hematopoietic growth factor support within 14 days prior to the first administration of ALK201.
• Serum pregnancy test result is negative for female subjects of childbearing potential during the screening period.

Exclusion criteria

• Adverse events related to prior anti-tumor therapy have not recovered to Grade ≤1 per NCI-CTCAE Version 6.0. Exceptions include alopecia, hypothyroidism stabilized with hormone replacement therapy, and Grade 2 toxicities judged by the Investigator to pose no safety risk (Grade 2 neuropathy is excluded).
• Use of strong cytochrome P450 (CYP) 3A4 inhibitors, strong CYP3A4 inducers, or relevant foods within 2 weeks or 5 half-lives prior to the first administration of ALK201 and combination therapy, whichever is longer.
• History of other malignancies besides the study disease within 5 years prior to enrollment, except malignancies cured by radical treatment without evidence of recurrence, such as basal cell carcinoma or squamous cell carcinoma of the skin, superficial bladder carcinoma, cervical carcinoma in situ, low-risk prostate cancer, and ductal carcinoma in situ of the breast.
• Presence of clinically symptomatic, poorly controlled, or recurrently drained pleural effusion, pericardial effusion, or ascites.
• Planned major surgery during study treatment, or subjects within the postoperative recovery period following major surgery. Subjects with prior major surgery must fully recover from surgical toxicities and/or complications to Grade ≤1 per CTCAE v6.0 before the first study drug administration; otherwise, they will be excluded.
• Evidence of severe or uncontrolled systemic diseases (e.g., decompensated respiratory, hepatic, or renal disorders).
• History of solid organ transplantation or hematopoietic stem cell transplantation.
• Administration of live attenuated vaccines within 4 weeks before the first dose of ALK201.
• Female subjects who are pregnant or breastfeeding.