Firmonertinib Combined With Definitive Radiotherapy in Stage III Unresectable EGFR Uncommon Mutant Pulmonary Adenocarcinoma

NCT07314216 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT172
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, Phase II clinical study aimed at evaluating the efficacy and safety of 160mg fimonertinib in combination with definitive radiotherapy for patients with EGFR uncommon driver mutation-positive, Stage III unresectable lung adenocarcinoma. The primary endpoint is Progression-Free Survival (PFS), assessed by the investigator according to RECIST 1.1 criteria, defined as the time from the first dose to objective disease progression or death (from any cause). Secondary endpoints include PFS by different mutation types, OS, ORR, DCR, as well as adverse events and their severity.

Conditions

Stage III; EGFR Uncommon Mutations; NSCLC (Non-small Cell Lung Carcinoma)

Keywords

unresectable Stage III lung adenocarcinoma; EGFR uncommon mutations; Firmonertinib; radiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  the time from the first dose of study treatment (or treatment initiation in single-arm trials) to disease progression or death from any cause, whichever occurs first.

  From enrollment until 30 months after the completion of treatment

Secondary Outcomes (5)

• Objective response rate

  From enrollment until 30 months after the completion of treatment

• Disease control rate

  From enrollment until 30 months after the completion of treatment

• Progression-Free Survival by Mutation Type

  From enrollment until 30 months after the completion of treatment

• Overall Survival

  From enrollment until 60 months after the completion of treatment

• AE

  From enrollment until 30 months after the completion of treatment, every 12 weeks

Study Arms (1)

Firmonertinib combined with definitive radiotherapy

EXPERIMENTAL

Patients in this arm will receive a combined regimen of Firmonertinib targeted therapy and definitive radiotherapy. The treatment consists of three phases: 1. Induction Phase: Oral Firmonertinib monotherapy for 12 weeks; 2. Combined Radiotherapy Phase: Firmonertinib concurrently with definitive thoracic radiotherapy for 6 weeks; 3. Consolidation Phase: Firmonertinib monotherapy continued until disease progression or unacceptable toxicity.

Drug: Firmonertinib; Radiation: Definitive Thoracic Radiotherapy

Interventions

Firmonertinib DRUG

Oral administration

Also known as: AST2818

Firmonertinib combined with definitive radiotherapy

Definitive Thoracic Radiotherapy RADIATION

Conformal radiotherapy delivered to the primary tumor and involved regional lymph nodes.

Also known as: IMRT, VMAT

Firmonertinib combined with definitive radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study-specific procedures;
• Age 18-75 years;
• ECOG performance status of 0 or 1 with no deterioration within the 2 weeks prior to enrollment, and a life expectancy of ≥12 weeks;
• Histologically or cytologically confirmed non-squamous non-small cell lung cancer;
• Assessed as having unresectable or inoperable locally advanced non-squamous non-small cell lung cancer suitable for definitive radiotherapy (Stage III according to AJCC 9th edition TNM staging);
• Presence of EGFR uncommon mutations (excluding 19del, L858R, T790M) confirmed by genetic testing in a tertiary grade A hospital; specific types are detailed in Appendix 11;
• No prior systemic anti-tumor therapy or radiotherapy for locally advanced non-small cell lung cancer before the first dose of the study drug, including chemotherapy, biologic therapy, targeted therapy, immunotherapy, or investigational drug therapy;
• At least one accurately measurable lesion according to RECIST 1.1, which has not been previously irradiated and was not biopsied during the screening period. If a subject has only one measurable lesion, biopsy of that lesion is permitted, provided the baseline imaging is performed at least 14 days after the biopsy;
• Female subjects must use highly effective contraception (see restrictions) for at least 2 weeks prior to the first dose, have a negative pregnancy test, must not be breastfeeding at the time of treatment initiation, OR must meet at least one of the following criteria at screening to demonstrate the absence of childbearing potential;
• Postmenopausal, defined as age over 50 years and amenorrhea for at least 12 months after cessation of all exogenous hormonal treatments;
• For women aged 50 years or younger, amenorrhea for 12 months or more after cessation of exogenous hormone therapy and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels within the institutional postmenopausal range;
• Irreversible surgical sterilization documented by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but excluding tubal ligation;
• Male subjects must be willing to use barrier contraception ;
• Ability to comply with the study protocol and follow-up procedures, and capable of oral medication intake

You may not qualify if:

• Pathological type is pulmonary squamous cell carcinoma or small cell lung cancer;
• Known history of hypersensitivity to the active or inactive excipients of firmonertinib, or to drugs with a similar chemical structure or class to the investigational drug;
• Confirmed presence of EGFR exon 19 deletion or exon 21 L858R mutation;
• Presence of metastatic disease, or assessed as unsuitable for definitive radiotherapy; or unable to undergo definitive radiotherapy due to extensive tumor volume resulting in normal tissue radiation doses exceeding dose constraints;
• NSCLC involving the superior sulcus, large cell neuroendocrine carcinoma (LCNEC), or sarcomatoid tumor;
• Prior to the first dose of the study drug, patients who have received any of the following treatments;
• Any prior EGFR-TKI therapy;
• Patients who have received intrapleural infusion therapy; these patients may be enrolled only after pleural effusion has been stable for 28 days or more;
• Major surgery within 28 days prior to the first dose of study drug (In China, major surgery is defined according to the Level 3 and Level 4 surgeries specified in the "Administrative Measures for the Clinical Application of Medical Technologies" implemented on May 1, 2009; see Appendix 5 for details);
• Treatment with strong CYP3A4 inhibitors or inducers within 7 days prior to the first dose, or patients who require continued use of these drugs during the study period (see Appendix 6 for drug list);
• Treatment with traditional Chinese medicine or Chinese patent medicine for anti-tumor indications within 7 days prior to the first dose, or patients who require continued use of these drugs during the study period;
• Concurrent use of medications known to prolong the QTc interval or that may induce Torsade de Pointes, and which require continued administration during the study period (see Appendix 8 for drug list);
• Discontinuation of other investigational drugs within less than 5 half-lives or 2 months (whichever is longer) prior to the first dose;
• Toxicities from prior anti-tumor therapy have not recovered to ≤ CTCAE Grade 1 prior to the first dose of the study drug (except for alopecia or chemotherapy-induced peripheral neuropathy ≤ CTCAE Grade 2);
• Patients with unstable pleural effusion;

Sponsors & Collaborators

• Hunan Cancer Hospital: lead

Study Sites (1)

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aflutinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Huai Liu, M.Med.

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Xingxiang Pu, M.D.

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Huai Liu

CONTACT

0731-89762321; liuhuai@hnca.org.cn

Xingxiang Pu

CONTACT

0731-89762300; puxingxiang@hnca.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: January 2, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)