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

Official title

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.

Overview

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.

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.

Interventions

• 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
• 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

Primary outcome measures

• TEAEs [Time frame: Up to 12 months]

Secondary outcome measures (6)

• Peak Plasma Concentration (Cmax) [Time frame: Up to 12 months]
• ADAs [Time frame: Up to 12 months]
• Area under the plasma concentration versus time curve (AUC) [Time frame: up to 12 months]
• Objective Response Rate(ORR) [Time frame: Up to 12 months]
• Disease Control Rate (DCR) [Time frame: Up to 12 months]
• Progression-FreeSurvival (PFS) [Time frame: Up to 12 months]

Eligibility criteria

Inclusion criteria

• The trial Participants themselves (and/or guardians) have understood and agreed to follow the study procedures and voluntarily signed the ICF;
• Men and women ≥18 and ≤75 years old on the day of signing the ICF;
• 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;
• 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;
• Expected survival ≥ 3 months;

Exclusion criteria

• Previously received EGFR- and/or MET-targeting ADCs and/or ADCs with topoisomerase I inhibitor as the payload;
• 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);
• 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;
• 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;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07603791 · ALK202-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗