A Study Evaluating Furmonertinib Plus Platinum-based Doublet Chemotherapy Versus Osimertinib in Patients With Epidermal Growth Factor Receptor (EGFR) Sensitizing Mutation-Positive Non-squamous Non-Small Cell Lung Cancer (NSCLC) and Brain Metastases

NCT06970639 | Recruiting Phase 3 DMC

• 1 other identifier: ALSC014AST2818
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a Phase III, international, multicenter, randomized, controlled, open-label clinical trial. The primary objective is to evaluate the efficacy and safety of furmonertinib plus platinum-based doublet chemotherapy (Arm A) versus osimertinib monotherapy (Arm B) in patients with EGFR sensitizing mutation-positive non-squamous non-small cell lung cancer (NSCLC) and brain metastases. Additionally, a proportion of subjects will receive furmonertinib monotherapy (Arm C) to further explore its efficacy and safety profile. Stage 1 is the safety run-in phase, planned to enroll approximately 30 subjects who will be randomized at a 1:1 ratio to receive either furmonertinib 80 mg QD plus platinum-based chemotherapy or furmonertinib 160 mg QD plus platinum-based chemotherapy, aiming to evaluate the safety and tolerability of different furmonertinib doses in combination with platinum-based chemotherapy. Stage 2 is the randomized controlled phase, in which approximately 350 subjects will be randomized in a 3:3:1 ratio (Arm A : Arm B : Arm C) to receive the investigational treatments.

Conditions

NSCLC Patients With Brain Metastasis

Keywords

EGFR; firmonertinib

Outcome Measures

Primary Outcomes (3)

• Adverse Events (AE)

  Safe import period

  Up to 4 years

• Serious Adverse Event (SAE)

  Safe import period

  Up to 4 years

• Progression-free survival (PFS)

  Randomized Controlled Phase：PFS assessed by BICR based on recist1.1; PFS was defined as the time from the date of randomization to the date of first documented disease progression (assessed according to RECIST v1.1 criteria) or death from any cause, whichever occurred first.

  Up to 4 years

Secondary Outcomes (15)

• Progression free survival (PFS) evaluated by researchers based on RECIST 1.1

  Up to 4 years

• Objective response rate (ORR)

  Up to 4 years

• Disease control rate (DCR)

  Up to 4 years

• Duration of Relief (DOR)

  Up to 4 years

• Overall survival (OS)

  Up to 4 years

Study Arms (2)

Furmonertinib combined with chemotherapy

EXPERIMENTAL

Furmonertinib Mesilate Tablets+Carboplatin Injection/Cisplatin for injection+Pemetrexed Disodium for Injection

Drug: Furmonertinib Mesilate Tablets; Drug: Carboplatin Injection; Drug: Cisplatin for injection; Drug: Pemetrexed Disodium for Injection

Osimertinib Mesylate Tablets

ACTIVE COMPARATOR

Osimertinib Mesylate Tablets

Drug: Osimertinib Mesylate Tablets

Interventions

Furmonertinib Mesilate Tablets DRUG

Usage and dosage: 80mg, 240mg, or 160mg QD orally Medication duration: A cycle of 21 days until intolerable toxicity, disease progression, death, or initiation of new anti-tumor therapy occurs

Furmonertinib combined with chemotherapy

Carboplatin Injection DRUG

Usage and dosage: Administer via IV infusion, with a dosage of AUC5, not exceeding 750 mg. Medication schedule: every 3 weeks as a cycle, D1 administration per cycle, immediate administration of carboplatin upon completion of pemetrexed infusion, intravenous infusion, carboplatin can be used for up to 4 cycles.

Furmonertinib combined with chemotherapy

Cisplatin for injection DRUG

Usage and dosage: Administer via IV infusion at a dose of 75 mg/m2. Medication schedule: Every 3 weeks as a cycle, with D1 administration per cycle. Cisplatin is administered approximately 30 minutes after the infusion of pemetrexed, via intravenous infusion. Adequate hydration therapy must be received before and after cisplatin treatment. Cisplatin can be used for up to 4 cycles.

Furmonertinib combined with chemotherapy

Pemetrexed Disodium for Injection DRUG

Usage and dosage: Intravenous (IV) infusion administration, dosage of 500 mg/m2 Medication schedule: Administer on the first day of each cycle (21 days per cycle, i.e. every 3 weeks) until intolerable toxicity, disease progression, death, or initiation of new anti-tumor therapy occurs.

Furmonertinib combined with chemotherapy

Osimertinib Mesylate Tablets DRUG

Usage and dosage: 80mg, QD administration Medication duration: A cycle of 21 days until intolerable toxicity, disease progression, death, or initiation of new anti-tumor therapy occurs

Osimertinib Mesylate Tablets

Eligibility Criteria

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

You may qualify if:

• Fully understand the trial and voluntarily sign the informed consent form;
• Age ≥18 years at the time of signing ICF, regardless of gender;
• Histologically/cytologically confirmed non-squamous NSCLC with brain parenchymal metastases assessed by BICR; Subjects with both brain parenchymal and leptomeningeal metastases are eligible. Subjects without brain metastases may be enrolled in the safety run-in phase.
• For subjects with brain metastases: clinically stable for ≥4 weeks prior to first dose AND no requirement for corticosteroids/anticonvulsants for ≥14 days prior to first dose; Investigator-confirmed no need for local therapy for brain metastases during screening.
• Confirmed EGFR sensitizing mutations (ex19del or L858R) via tumor tissue/cytology/blood testing;
• No prior systemic anti-tumor therapy for advanced/metastatic NSCLC; Subjects who received (neo)adjuvant chemotherapy or definitive chemoradiotherapy must have disease recurrence/progression ≥6 months after completion;
• ≥1 measurable intracranial AND extracranial lesion(s) per RECIST v1.1 without prior local treatment;
• ECOG PS 0-1 with no deterioration within 2 weeks prior to first dose, and life expectancy ≥3 months;
• Adequate bone marrow and organ function (no transfusion/G-CSF within 2 weeks prior to first dose);
• All prior treatment-related toxicities resolved to ≤Grade 1 (per NCI CTCAE v5.0) except alopecia (≤Grade 2) or peripheral neuropathy (≤Grade 2);
• Women of childbearing potential (WOCBP) must have negative serum pregnancy test within 7 days prior to first dose, be non-lactating, and use effective contraception from ICF signing until 6 months after last dose. Male subjects with fertile partners must use contraception during the same period.

You may not qualify if:

• The tumor histology or cytology confirmed that the combination of neuroendocrine carcinoma, sarcomatoid carcinoma or squamous cell carcinoma was more than 10%;
• Known subjects with ALK positive, ros1 positive, RET fusion positive, ntrk fusion positive, BRAF V600 mutation, met exon 14 skipping variant and other approved drugs for this target;
• Subjects with meningeal metastasis but no brain parenchymal metastasis confirmed by MRI and / or CSF malignant cell examination;
• Subjects who have previously received any of the following treatments:
• Have received any systemic anti-tumor therapy targeting EGFR in the past, including those in clinical research stage (including EGFR TKI, monoclonal antibody, bispecific antibody, etc.);
• Previously received systemic antitumor therapy (such as chemotherapy, targeted therapy, immunotherapy, etc.) for locally advanced / metastatic non-small cell lung cancer;
• Received \> 30 Gy of chest radiotherapy within 6 months before the first dose; Received non thoracic radiotherapy of \>30 Gy within 4 weeks before the first dose; Received palliative radiotherapy ≤ 30Gy within 2 weeks before the first dose; Previous brain radiotherapy;
• Chinese patent medicine that has received non-specific immune modulators (including but not limited to interferon and IL-2) and approved anti-tumor indications within 2 weeks before the first administration;
• Have used any strong inhibitor of cytochrome P450 3A4 (CYP3A4) within 7 days before the first administration or any strong inducer of CYP3A4 within 21 days before the first administration;
• Other malignant tumors in addition to the primary tumor; Skin basal cell or squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, breast ductal carcinoma in situ and papillary thyroid cancer that can be treated locally and have been cured can be selected; Subjects with a history of other malignancies and who have been cured for ≥ 3 years after radical treatment can be enrolled;
• Brain metastasis subjects with known brain stem metastasis, spinal cord metastasis and / or compression; Subjects with acute or progressive intracranial hypertension related symptoms during the screening period; Subjects with brain herniation or near brain herniation; Brain imaging revealed significant brain midline deviation and other subjects requiring urgent local treatment;
• According to CTCAE 5.0, there were subjects with grade 2 headache, vomiting, papilledema, etc. caused by increased intracranial pressure during the screening period; Subjects with grade 2 sensory / motor impairment and visual field damage caused by brain metastasis during the screening period; Subjects with mental symptoms (such as dementia, sluggish reaction, etc.) or seizures caused by brain metastasis during the screening period; Subjects who can control relevant central nervous system symptoms ≤ 1 grade by steroid hormones or anticonvulsants can be enrolled;
• The tumor invades the surrounding important organs and blood vessels (such as the heart, esophagus, superior vena cava, etc.) or has the risk of esophago tracheal fistula or esophago pleural fistula;
• Cardiovascular and cerebrovascular disease or cardiovascular and cerebrovascular risk factors exist.
• There are uncontrollable systemic diseases.

Sponsors & Collaborators

• Allist Pharmaceuticals, Inc.: lead

Study Sites (1)

Guangdong Provincial People's Hospital

Guangdong, Guangzhou, China

RECRUITING

MeSH Terms

Interventions

Carboplatin; Cisplatin; Injections; Pemetrexed; osimertinib

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Drug Administration Routes; Drug Therapy; Therapeutics; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: May 14, 2025
• Study Start: September 26, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: February 12, 2026

Record last verified: 2025-03

Locations

CN (1)