Phase II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of ALK202 for Injection in Combination With Drugs in NSCLC Participants.

An Open, Multicenter Phase II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of ALK202 for Injection in Combination With Different Drugs in NSCLC Participants.

This study is an open, multicenter, phase II clinical study for evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ALK202 for injection combined with different drugs in participants with locally advanced or metastatic NSCLC. The study consists of two phases: the Phase IIa (dose escalation) and the Phase IIb (efficacy extension).

Phase IIa (dose escalation) :This stage consists of 3 cohorts, which will respectively recruit participants meeting the criteria for each cohort who have locally advanced or metastatic NSCLC, to complete the dose escalation for each combination regimen.

The Escalation cohort 1: participants with locally advanced or metastatic EGFR mutation (EGFRmut) non-squamous NSCLC who have failed previous EGFR-TKI treatment, and they will receive ALK202 combined with Osimertinib Mesylate Tablets.

The Escalation cohort 2: participants with locally advanced or metastatic EGFR wild-type (EGFRwt) NSCLC who have failed previous standard treatment, and they will receive ALK202 combined with Ivonescimab Injection.

The Escalation cohort 3: participants with locally advanced or metastatic EGFRwt NSCLC who have failed previous standard treatment, and they will receive ALK202 combined with Ivonescimab Injection and Carboplatin Injection.

Phase IIb (Efficacy Extension ) In this phase, three cohorts are initially planned. They will respectively recruit participants with locally advanced or metastatic NSCLC who meet the criteria of each combination regimen, to evaluate the efficacy of ALK202 combined with different drugs, and further assess its safety.

Extension Cohort 1:participants with EGFRmut non-squamous NSCLC that has not received systemic palliative treatment; Extension Cohort 2: participants with NSCLC driver gene negative NSCLC and PD-L1 expression ≥ 1% and high c-MET expression that has not received systemic treatment; Extension Cohort 3: participants with NSCLC driver gene negative NSCLC and PD-L1 expression < 1% and high c-MET expression that has not received systemic treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC (Advanced Non-small Cell Lung Cancer)
• Intervention / Treatment: Drug: ALK202 for injection; Combination product: Osimertinib Mesylate Tablets; Combination product: Ivonescimab Injection; Combination product: carboplatin injection

Detailed Description

This study is an open, multicenter, phase II clinical study for evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ALK202 for injection combined with different drugs in participants with locally advanced or metastatic NSCLC. The study consists of two phases: the Phase IIa (dose escalation) and the Phase IIb (efficacy extension).

Phase IIa (dose escalation) :This stage consists of 3 cohorts, which will respectively recruit participants meeting the criteria for each cohort who have locally advanced or metastatic NSCLC, to complete the dose escalation for each combination regimen.

The Escalation cohort 1: participants with locally advanced or metastatic EGFR mutation (EGFRmut) non-squamous NSCLC who have failed previous EGFR-TKI treatment, and they will receive ALK202 combined with Osimertinib Mesylate Tablets.

The Escalation cohort 2: participants with locally advanced or metastatic EGFR wild-type (EGFRwt) NSCLC who have failed previous standard treatment, and they will receive ALK202 combined with Ivonescimab Injection.

The Escalation cohort 3: participants with locally advanced or metastatic EGFRwt NSCLC who have failed previous standard treatment, and they will receive ALK202 combined with Ivonescimab Injection and Carboplatin Injection.

Phase IIb (Efficacy Extension ) In this phase, three cohorts are initially planned. They will respectively recruit participants with locally advanced or metastatic NSCLC who meet the criteria of each combination regimen, to evaluate the efficacy of ALK202 combined with different drugs, and further assess its safety.

Extension Cohort 1:participants with EGFRmut non-squamous NSCLC that has not received systemic palliative treatment; Extension Cohort 2: participants with NSCLC driver gene negative NSCLC and PD-L1 expression ≥ 1% and high c-MET expression that has not received systemic treatment; Extension Cohort 3: participants with NSCLC driver gene negative NSCLC and PD-L1 expression < 1% and high c-MET expression that has not received systemic treatment.

Expansion cohort 1: two groups participants treated with ALK202 at two different doses in combination with Osimertinib Mesylate Tablets. Eachdose group enrolled 30 trial participants, totaling 60 participants, and they are randomly assigned in a 1:1 ratio. The ALK202 treatment regimen involves intravenous infusion, on Day 1 or on Days 1 and 8, every 3 weeks or twice, until disease progression, intolerability, or death occurs. The Osimertinib Mesylate Tablets treatment regimen is 80 mg, orally, once daily, until disease progression, intolerability, or death.

Expansion cohort 2: two groups participants treated with ALK202 at two different doses in combination with Ivonescimab Injection. Each dose group includes 30 participants, totaling 60 participants, and they are randomly assigned in a 1:1 ratio. The ALK202 treatment regimen involves intravenous infusion, on Day 1 or on Days 1 and 8, every 3 weeks or twice. Until the disease progresses or becomes intolerable or leads to death; the Ivonescimab Injection treatment regimen is 20 mg/kg, administered intravenously, once every 3 weeks, until the disease progresses or becomes intolerable or leads to death.

Expansion cohort 3: participants will select two dosing regimens from the two-drug combination of ALK202+Ivonescimab Injection or the three-drug combination of ALK202 +Ivonescimab Injection+ Carboplatin for exploration based on the preliminary safety and efficacy results of ascending cohort 2 and ascending cohort 3.

• Study Type: Interventional
• Enrollment (Estimated): 252
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mei Tian, Master; Phone Number: +8615800960592; Email: mtian@allinkbio.com
• Study Contact Backup: Name: Shuntong Duan, Master; Phone Number: +8619921555831; Email: stduan@allinkbio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The trial Participants themselves (and/or guardians) have understood and agreed to follow the study procedures and voluntarily signed the ICF;
2. Men and women ≥18 and ≤75 years old on the day of signing the ICF;
3. The trial participants agree to provide fresh or archived tumor tissues for the detection of the expression status of driving genes or proteins (such as EGFR expression, c-MET expression, and PD-L1 expression status, etc.). If the trial participants are unable to provide the required tumor tissues for testing, their participation in the trial must be approved by the sponsor;
4. The presence of at least one measurable lesion is required according to the RECIST v1.1 criteria. A neoplastic lesion that has received local treatment, such as radiotherapy, can be taken as a target lesion if disease progression is proved by imaging;
5. Expected survival ≥ 3 months;

Exclusion Criteria:

1. Previously received EGFR- and/or MET-targeting ADCs and/or ADCs with topoisomerase I inhibitor as the payload;
2. Participated in other interventional clinical trials within 4 weeks or 5 drug half-lives before the first dose of ALK202 (whichever is shorter). Note: Patients who have participated in another interventional clinical trial, even if they are still in the survival follow-up period of the previous trial, may be enrolled in this study provided that the first dose of ALK202 is to be administered ≥5 half-lives or 4 weeks from the last dose of the trial drug (whichever is shorter);
3. Received chemotherapy, targeted therapy, immunotherapy, interventional procedure, or other systemic antitumor therapy within 4 weeks (Note: 6 weeks for nitrosourea or mitomycin C, 2 weeks or 5 half-lives of the drugs [whichever is shorter] for oral fluorouracil and small-molecule targeted drugs, and 2 weeks for Chinese medicines with anti-tumor indications) prior to the first dose of ALK202;
4. Received radical radiotherapy, whole-brain radiotherapy, or bone marrow irradiation > 30% within 4 weeks before the first dose of ALK202; or palliative radiation (including stereotactic radiotherapy) of non-target lesions for symptom relief purposes within 2 weeks prior to the first dose;
5. Took drugs or food that strongly inhibit or induce the cytochrome P450 (CYP) isoenzyme, CYP3A4 within 2 weeks or within 5 half-lives prior to the first dose of ALK202, whichever is longer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cohort1; Participants with Non-squamous NSCLC with EGFR mutation that has not received systemic palliative treatment, using the ALK202 combine with the Osimertinib Mesylate Tablets treatment	Drug: ALK202 for injection; This study employs combined medication. The participants in different groups are treated for non-small cell lung cancer using ALK202 in combination with various drugs.; Combination product: Osimertinib Mesylate Tablets; Combination Drug 1: Osimertinib Mesylate Tablets, ALK202 combine with Osimertinib Mesylate Tablets for cohort1 enrolled participants
Experimental: cohort2; Participants with NSCLC (non-small cell lung cancer) who have not received systemic palliative treatment, with PD-L1 expression ≥ 1% and high c-MET expression, and without any driver gene mutations; using the ALK202 combine with the Ivonescimab Injection treatment	Drug: ALK202 for injection; This study employs combined medication. The participants in different groups are treated for non-small cell lung cancer using ALK202 in combination with various drugs.; Combination product: Ivonescimab Injection; Combination product 2: Ivonescimab Injection, ALK202 combine with Ivonescimab Injection for cohort2 enrolled participants
Experimental: cohort3; Participants with NSCLC (non-small cell lung cancer) who have not received systemic palliative treatment, with PD-L1 expression < 1% and high c-MET expression, and without any driver gene mutations; using the ALK202 combine with the Ivonescimab Injection and carboplatin injection treatment	Drug: ALK202 for injection; This study employs combined medication. The participants in different groups are treated for non-small cell lung cancer using ALK202 in combination with various drugs.; Combination product: Ivonescimab Injection; Combination product 2: Ivonescimab Injection, ALK202 combine with Ivonescimab Injection for cohort2 enrolled participants; Combination product: carboplatin injection; Combination product 2: Ivonescimab Injection, ALK202 combine with Ivonescimab Injection and carboplatin injection for cohort3 enrolled participants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TEAEs	Participants with Treatment-Related Adverse Events as Assessed by CTCAE v6.0	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	PK parameters after single andmultiple doses	Up to 12 months
ADAs	The generation of anti-drug antibodies	Up to 12 months
Area under the plasma concentration versus time curve (AUC)	PK parameters after single andmultiple doses	up to 12 months
Objective Response Rate(ORR)	Objective Response Rate(ORR) calculated based onthe Response Evaluation Criteria InSolid Tumors (RECIST) v1.1 criteria	Up to 12 months
Disease Control Rate (DCR)	DCR calculated based onthe Response Evaluation Criteria InSolid Tumors (RECIST) v1.1 criteria	Up to 12 months
Progression-FreeSurvival (PFS)	PFS calculated based onthe Response Evaluation Criteria InSolid Tumors (RECIST) v1.1 criteria	Up to 12 months

Collaborators and Investigators

• Sponsor: Shanghai Allink Biotherapeutics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: May 12, 2026
• First Submitted That Met QC Criteria: May 17, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Organic Chemicals; Therapeutics; Drug Administration Routes; Drug Therapy; Coordination Complexes; Carboplatin; Injections; osimertinib
• Other Study ID Numbers: ALK202-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No