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

NCT06955988 | Recruiting Phase 1

• 1 other identifier: ALSC001AST2303
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Locally Advanced or Metastatic Non-small Cell Lung Cancer

Keywords

EGFR L858R-C797S; Del19-C797S

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (3)

• Peak Time (Tmax)

  Up to 2 years

• Peak Plasma Concentration (Cmax)

  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

Study Arms (5)

AST2303 Tablets(ABK3376 Tablets) ，25mg

EXPERIMENTAL

AST2303 Tablets(ABK3376 Tablets) ，25mg

Drug: AST2303 Tablets(ABK3376 Tablets) ，25mg

AST2303 Tablets(ABK3376 Tablets) ，50mg

EXPERIMENTAL

AST2303 Tablets(ABK3376 Tablets) ，50mg

Drug: AST2303 Tablets(ABK3376 Tablets) ，50mg

AST2303 Tablets(ABK3376 Tablets) ，75mg

EXPERIMENTAL

AST2303 Tablets(ABK3376 Tablets) ，75mg

Drug: AST2303 Tablets(ABK3376 Tablets) ，75mg

AST2303 Tablets(ABK3376 Tablets) ，100mg

EXPERIMENTAL

AST2303 Tablets(ABK3376 Tablets) ，100mg

Drug: AST2303 Tablets(ABK3376 Tablets) ，100mg

AST2303 Tablets(ABK3376 Tablets) ，125mg

EXPERIMENTAL

AST2303 Tablets(ABK3376 Tablets) ，125mg

Drug: AST2303 Tablets(ABK3376 Tablets) ，125mg

Interventions

AST2303 Tablets(ABK3376 Tablets) ，25mg DRUG

Usage and dosage: 25mg, oral on an empty stomach Duration of medication: oral once a day, 21 days as a cycle

AST2303 Tablets(ABK3376 Tablets) ，25mg

AST2303 Tablets(ABK3376 Tablets) ，50mg DRUG

Usage and dosage: 50mg, oral on an empty stomach Duration of medication: oral once a day, 21 days as a cycle

AST2303 Tablets(ABK3376 Tablets) ，50mg

AST2303 Tablets(ABK3376 Tablets) ，75mg DRUG

Usage and dosage: 75mg, oral on an empty stomach Duration of medication: oral once a day, 21 days as a cycle

AST2303 Tablets(ABK3376 Tablets) ，75mg

AST2303 Tablets(ABK3376 Tablets) ，100mg DRUG

Usage and dosage: 100mg, oral on an empty stomach Duration of medication: oral once a day, 21 days as a cycle

AST2303 Tablets(ABK3376 Tablets) ，100mg

AST2303 Tablets(ABK3376 Tablets) ，125mg DRUG

Usage and dosage: 125mg, oral on an empty stomach Duration of medication: oral once a day, 21 days as a cycle

AST2303 Tablets(ABK3376 Tablets) ，125mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have fully understood this test and voluntarily sign the informed consent
• Age ≥ 18 at the time of signing the informed consent, regardless of gender
• Patients with non-small cell lung cancer confirmed by tissue / cytology.
• According to recist1.1 criteria, the presence of at least one target lesion without local treatment was assessed by the investigator
• Agree to provide blood samples and / or tumor tissue samples (fresh tissue or paraffin embedded tissue) for genetic testing
• 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)
• The ECoG physical status score is 0 or 1
• Expected survival time ≥ 12 weeks
• Have normal swallowing function
• 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

You may not qualify if:

• Previously received antitumor therapy targeting the c797s mutation
• Carry any other known driver gene alterations
• 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;
• 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
• 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
• Local (non bone lesions) radiotherapy within 4 weeks before the first dose, or bone radiotherapy within 2 weeks before the first dose;
• Other malignant tumors besides the primary tumor
• 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
• The tumor invades the surrounding important organs and blood vessels or has the risk of esophago tracheal fistula or esophago pleural fistula
• 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
• Presence of cardiovascular and cerebrovascular disease or cardiovascular and cerebrovascular risk factors
• Uncontrollable systemic diseases
• 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
• 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
• Severe acute or chronic infection

Sponsors & Collaborators

• Allist Pharmaceuticals, Inc.: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Shanghai Allist Pharmaceuticals Co., Ltd Shanghai Allist Pharmaceuticals Co., Ltd

CONTACT

021-80423288; zhenhua.gong@allist.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2025
• First Posted: May 2, 2025
• Study Start: March 4, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 12, 2026

Record last verified: 2025-03

Locations

CN (1)