A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AST2303 Tablets (ABK3376 Tablets) in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AST2303 Tablets (ABK3376 Tablets) in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

This study is a multicenter, single arm, open label, phase I clinical trial, including dose escalation (phase IA) and dose expansion (phase IB). This study aimed to evaluate the safety, tolerability, PK characteristics and preliminary antitumor activity of ast2303 tablets (abk3376 tablets) in subjects with locally advanced or metastatic non-small cell lung cancer. A safety review committee (SRC) was established in this study, which will review the safety, efficacy, pharmacokinetics and other data obtained from the study, and make decisions on key issues such as dose escalation and dose expansion.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced or Metastatic Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: AST2303 Tablets(ABK3376 Tablets) ，25mg; Drug: AST2303 Tablets(ABK3376 Tablets) ，50mg; Drug: AST2303 Tablets(ABK3376 Tablets) ，75mg; Drug: AST2303 Tablets(ABK3376 Tablets) ，100mg; Drug: AST2303 Tablets(ABK3376 Tablets) ，125mg

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Shanghai Allist Pharmaceuticals Co., Ltd Shanghai Allist Pharmaceuticals Co., Ltd; Phone Number: 021-80423288; Email: zhenhua.gong@allist.com.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Recruiting
      • Shanghai Chest Hospital
      • Contact: Chen zhonglin Chen zhonglin，research associate, research associate; Phone Number: 021-22200000; Email: chestgcp@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Have fully understood this test and voluntarily sign the informed consent
2. Age ≥ 18 at the time of signing the informed consent, regardless of gender
3. Patients with non-small cell lung cancer confirmed by tissue / cytology.
4. According to recist1.1 criteria, the presence of at least one target lesion without local treatment was assessed by the investigator
5. Agree to provide blood samples and / or tumor tissue samples (fresh tissue or paraffin embedded tissue) for genetic testing
6. The subject's bone marrow and organ functions are good (no blood transfusion or hematopoietic growth factor treatment within 2 weeks before the first administration)
7. The ECoG physical status score is 0 or 1
8. Expected survival time ≥ 12 weeks
9. Have normal swallowing function
10. Female subjects with fertility must have a serum pregnancy test within 7 days before the first administration, and the result is negative, and must be non lactating. For female subjects with fertility and male subjects with reproductive potential, effective contraceptive measures were taken from the signing of informed consent to 6 months after the last Administration

Exclusion Criteria:

1. Previously received antitumor therapy targeting the c797s mutation
2. Carry any other known driver gene alterations
3. Have received any systemic anti-tumor treatment (including anti-tumor drugs in clinical research stage) within 2 weeks before the first administration or within 5 half lives of the drug (whichever is longer); Or receiving anti-tumor drugs with long half-life, such as immune checkpoint inhibitors, within 4 weeks before the first administration; Or received cytotoxic drugs with significant delayed toxicity, such as mitomycin C, within 6 weeks before the first administration;
4. Have received non-specific immunomodulatory agents, traditional Chinese medicine or traditional Chinese medicine preparations with approved anti-tumor indications within 2 weeks before the first administration
5. Strong inhibitors of CYP3A, P-gp or BCRP were used within 7 days before the first administration, or strong inducers of CYP3A, P-gp or BCRP were used within 3 weeks
6. Local (non bone lesions) radiotherapy within 4 weeks before the first dose, or bone radiotherapy within 2 weeks before the first dose;
7. Other malignant tumors besides the primary tumor
8. Subjects known to have meningeal metastasis, brainstem metastasis, spinal cord metastasis and / or compression, active brain metastasis. For brain metastasis subjects who have received local treatment in the past, if they are clinically stable for at least 4 weeks before the first administration of study treatment and do not need to use glucocorticoids or anticonvulsants for at least 14 days before the first administration of study treatment, they can participate in the study
9. The tumor invades the surrounding important organs and blood vessels or has the risk of esophago tracheal fistula or esophago pleural fistula
10. The toxicity of previous anti-tumor treatment has not returned to grade ≤ 1 (NCI CTCAE version 5.0 evaluation), except for grade ≤ 2 alopecia and peripheral neuropathy
11. Presence of cardiovascular and cerebrovascular disease or cardiovascular and cerebrovascular risk factors
12. Uncontrollable systemic diseases
13. There is a history of (non infectious) interstitial lung disease (ILD) or non infectious pneumonia requiring steroid treatment; Currently have ILD or non infectious pneumonia; Suspected ILD or noninfectious pneumonia that could not be excluded by imaging examination was present at screening
14. Pulmonary complications lead to clinically serious lung damage, including but not limited to the following: A. any underlying lung disease; b. Any autoimmune, connective tissue or inflammatory disease that may involve the lungs; c. Previous unilateral pneumonectomy
15. Severe acute or chronic infection
16. Being under long-term systemic corticosteroid treatment with prednisone > 10 mg/ day or equivalent anti-inflammatory active drugs or any form of immunosuppressive treatment before the first administration. Subjects who need to use bronchodilators, inhaled or topical steroids or local steroid injections for treatment or as preventive medication for hypersensitivity reactions (such as medication before CT examination, etc.) can be included in the study
17. Subjects who had undergone major surgery within 4 weeks before the first dose or were expected to undergo major surgery during the study period
18. Bleeding symptoms with significant clinical significance or obvious bleeding tendency within 4 weeks before the first administration, such as gastrointestinal bleeding, gastric ulcer bleeding, active hemoptysis, etc
19. It is known that there are serious gastrointestinal dysfunction: such as untreated recurrent diarrhea, moderate to severe atrophic gastritis, gastrointestinal obstruction, Crohn's disease, ulcerative colitis, gastrointestinal perforation, etc
20. Known to have a history of hypersensitivity to the ingredients of the preparation used in the test
21. Pregnant or lactating women or women planning to become pregnant during the study
22. In the judgment of the investigator, the subject has other factors that may affect the results of the study or cause the forced termination of the study, such as alcohol abuse, drug abuse, suffering from other serious diseases (including mental diseases) requiring combined treatment, serious abnormal laboratory test values, family or social factors and other conditions that may affect the safety of the subject or the collection of test data, etc

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AST2303 Tablets(ABK3376 Tablets) ，25mg	Drug: AST2303 Tablets(ABK3376 Tablets) ，25mg; Usage and dosage: 25mg, oral on an empty stomach Duration of medication: oral once a day, 21 days as a cycle
Experimental: AST2303 Tablets(ABK3376 Tablets) ，50mg	Drug: AST2303 Tablets(ABK3376 Tablets) ，50mg; Usage and dosage: 50mg, oral on an empty stomach Duration of medication: oral once a day, 21 days as a cycle
Experimental: AST2303 Tablets(ABK3376 Tablets) ，75mg	Drug: AST2303 Tablets(ABK3376 Tablets) ，75mg; Usage and dosage: 75mg, oral on an empty stomach Duration of medication: oral once a day, 21 days as a cycle
Experimental: AST2303 Tablets(ABK3376 Tablets) ，100mg	Drug: AST2303 Tablets(ABK3376 Tablets) ，100mg; Usage and dosage: 100mg, oral on an empty stomach Duration of medication: oral once a day, 21 days as a cycle
Experimental: AST2303 Tablets(ABK3376 Tablets) ，125mg	Drug: AST2303 Tablets(ABK3376 Tablets) ，125mg; Usage and dosage: 125mg, oral on an empty stomach Duration of medication: oral once a day, 21 days as a cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event, AE	AE will be classified based on the latest version of the Medical Dictionary for Regulatory Activities (MedDRA) of the International Conference on Harmonisation of Registration Techniques for Medicinal Products for Human Use (ICH), and graded according to CTCAE 5.0.	Up to 2 years
Serious Adverse Event (SAE)		Up to 2 years
Adverse Events of Special Concern (AESI)		Up to 2 years
Objective response rate (ORR)	ORR is defined as the proportion of subjects confirmed as CR or PR to the total number of subjects, and the confirmation of remission is based on a follow-up evaluation conducted at least 28 days apart using the RECIST v1.1 evaluation criteria.	Up to 2 years
Disease Control Rate (DCR)	DCR is defined as the sum of the proportions of subjects whose disease is confirmed to have improved (including CR, PR) or stabilized (SD) after the start of treatment.	Up to 2 years
Duration of Relief (DOR)	DOR is defined as the time from the first recorded CR or PR to the first recorded imaging of disease progression (evaluated according to RECIST v1.1 criteria) or death from any cause (whichever occurs first) in a subject confirmed as ORR. Subjects who did not report disease progression or death during analysis will be subject to deletion on the date of the last tumor assessment.	Up to 2 years
Progression free survival (PFS)	PFS is defined as the time from the date of first medication to the date of first recorded disease progression (evaluated according to RECIST v1.1 criteria) or death from any cause (whichever occurs first).	Up to 2 years
Overall survival (OS)	OS is defined as the time from the date of initial medication to the date of death from any cause (whichever occurs first). Subjects who were not reported as deceased during the analysis, or subjects who were reported dead but had an unknown date of death (i.e. missing year, month, day, etc.), will be deleted from the last known date of survival.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Peak Plasma Concentration (Cmax)	Up to 2 years
Peak Time (Tmax)	Up to 2 years
From 0 to the last measurable time point t, the area under the drug time curve (AUC0-t)	Up to 2 years

Collaborators and Investigators

• Sponsor: Allist Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: April 11, 2025
• First Submitted That Met QC Criteria: April 24, 2025
• First Posted (Actual): May 2, 2025

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: EGFR L858R-C797S; Del19-C797S
• 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
• Other Study ID Numbers: ALSC001AST2303

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No