Andamertinib With or Without Platinum-doublet Chemotherapy Versus Platinum-doublet Chemotherapy in Patients With NSCLC Harboring Atypical EGFR Mutations (KANNON-5)

An Open-label, Randomized, Multicenter Phase II/III Study to Evaluate the Efficacy and Safety of Andamertinib With or Without Platinum-doublet Chemotherapy Versus Platinum-doublet Chemotherapy in Patients With Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Harboring Atypical EGFR Mutations Who Have Not Received Prior Systematic Therapy

This study is an open-label, randomized, multicenter phase II/III clinical trial designed to evaluate the efficacy, safety, and tolerability of Andamertinib with or without platinum-based chemothsrapy versus platinum-based chemotherapy in previously untreated participants with locally advanced or metastatic non-squamous NSCLC harboring EGFR atypical mutations. The study comprises two stages: phase II (dose-exploration stage) and phase III (pivotal study stage)

Study Overview

• Status: Recruiting
• Conditions: Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: PLB1004

Detailed Description

This a three-stage study consist a Screening Phase (Day -28 to -1), a Treatment Phase (until treatment discontinuation), and a Follow-up Phase (including end of treatment visit (EOT),end of study visit(EOS), safety follow-up and survival follow-up).

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haimeng Li; Phone Number: +86 17610831060; Email: lihaimeng@pearlbio.cn

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • Sun Yat-sen University Cancer Center
    • Contact: LI Zhang; Phone Number: +86 13948537070; Email: zhangli@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years at the time of ICF signing.
2. Histologically or cytologically confirmed, unresectable locally advanced (Stage IIIB or IIIC) or metastatic (Stage IV) non-squamous non-small cell lung cancer (NSCLC).
3. Confirmed EGFR atypical mutation.
4. No prior systemic therapy for locally advanced or metastatic NSCLC.
5. At least one measurable lesion as defined by RECIST v1.1.
6. ECOG PS ≤1.
7. Life expectancy≥12 weeks.
8. Adequate organ function confirmed within 7 days prior to the first dose of study treatment
9. Female participants must use adequate contraceptive measures during study participation and for 90 days after the last dose of study treatment and must not be breastfeeding; female subjects not of childbearing potential must meet at least one of the following criteria at screening: Postmenopausal status; Documentation of irreversible surgical sterilization.
10. Non-sterilized males: Abstinence or contraception use; No sperm donation.
11. Willing and able to provide signed ICF and to comply with all requirements and restrictions listed in the ICF and this study protocol.

Exclusion Criteria:

1. Presence of specific genetic alterations for which approved targeted therapies are available.
2. Recent participation (within 28 days) in another interventional clinical trial.
3. Major surgery within 28 days prior to study entry or planned during the study period.
4. Recent use of anti-tumor traditional proprietary medicine or local anti-tumor therapy.
5. Need for specific concomitant medications (e.g., metformin) that cannot be paused during the study.
6. History of another active malignancy within the past 5 years (except for specific cured cancers).
7. Toxicities from prior therapy have not recovered to acceptable levels.
8. Presence of symptomatic or uncontrolled brain metastases, carcinomatous meningitis, or spinal cord compression.
9. Symptomatic and uncontrolled third-space fluid accumulations (e.g., pleural effusion, ascites).
10. Severe cardiovascular/cerebrovascular disease or risk factors (e.g., heart failure, history of myocardial infarction, QT prolongation, uncontrolled hypertension, etc.).
11. History or presence of interstitial lung disease, or drug/radiation-related pneumonitis.
12. Active autoimmune or inflammatory diseases.
13. Active, uncontrolled infection (including HBV, HCV, HIV, syphilis, tuberculosis, etc.).
14. Gastrointestinal disorders or surgery affecting drug ingestion or absorption.
15. Active keratitis or ulcerative keratitis.
16. History of hypersensitivity to the study drug, its analogs, or chemotherapy drugs (pemetrexed/platinum agents).
17. Recent administration (within 30 days) of a live attenuated vaccine.
18. Psychiatric disorders or substance abuse potentially affecting compliance.
19. Any other condition deemed by the investigator as unsuitable for study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Andamertinib with or without platinum-based chemothsrapy versus platinum-based chemotherapy; PLB1004, oral, QD Platinum-based chemotherapy， injection, once every 21-day	Drug: PLB1004; Andamertinib with or without platinum-based chemothsrapy versus platinum-based chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).	In phase II，Incidence of Treatment-Emergent Adverse Events (TEAEs)	Up to 3 years
RP3D or recommended phase 3 treatment regimen	In phase II, choose the RP3D per gained safety and efficacy data	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	To evaluate the Overall Response Rate (ORR) which is defined by investigator as the proportion of subjects with confirmed best overall response of complete response or partial response per RECIST v1.1	Up to 3 years
Duration of Response(DOR)	DOR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes frst	up to 3 years
Disease Control Rate(DCR)	The percentage of tumor patients achieving complete remission (CR), partial remission (PR), or stable disease (SD) following treatment, relative to the total number of evaluable subjects	up to 3 years
Progression-Free Survival(PFS)	PFS is defined as the time from the date the first dose until the date of objective disease progression or death by cause whichever comes first, based on investigator review according to RECIST v1.1	up to 3 years
6-month Progression-Free Survival Rate	The proportion of subjects who did not experience disease progression or death within 6 months after receiving treatment.	up to 3 years
6-month Overall Survival Rate	The proportion of subjects who did not experience death within 6 months after receiving treatment.	up to 3 years
Assess the PK characteristics of Andamertinib	Plasma concentration of Andamertinib	On cycle1of day 1and cycle3of day1, samples were collected within 2 hours prior to dosing and 4 hours post-dosing,On Day 1of Cycle 2, Cycle 5, Cycle 7, and all subsequent odd-numbered cycles collected within 2hours prior to dosing(each cycle is 21days)

Collaborators and Investigators

• Sponsor: Avistone Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: December 18, 2025
• First Submitted That Met QC Criteria: January 2, 2026
• First Posted (Actual): January 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Lung Cancer; EGFR; EGFR ex20ins; PACC; L861Q; Non-Small-Cell Lung Cance
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: PLB1004-II/III-01

Drug and device information, study documents

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