Firmonertinib versus placebo as additional treatment after surgery for stage IB–IIIB non‑small cell lung cancer with uncommon EGFR mutations

A Global Phase 3, Double-Blind, Randomized, Controlled Multicenter Study to Assess the Efficacy and Safety of Firmonertinib Versus Placebo for Adjuvant Treatment in Participants With Stage IB - IIIB NSCLC With Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations, Following Complete Surgical Resection With or Without Adjuvant Chemotherapy (FIRMOST)

This trial will test whether taking firmonertinib after complete lung cancer surgery helps prevent recurrence in people with stage IB–IIIB NSCLC that has uncommon EGFR mutations.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 338 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Allist Pharmaceuticals, Inc. (industry)
• Drugs / interventions: chemotherapy, radiation, firmonertinib
• Locations: 2 sites (Beijing, Beijing Municipality and 1 other locations)
• Trial ID: NCT07010419 on ClinicalTrials.gov

What this trial studies

This is a global, phase 3, double‑blind, randomized trial that will enroll about 338 participants who have undergone complete (R0) resection for stage IB–IIIB non‑small cell lung cancer with documented uncommon EGFR mutations. Participants are randomized 1:1 to receive firmonertinib 240 mg once daily or matching placebo in 21‑day cycles and will be treated until unacceptable toxicity, withdrawal, recurrence, or other prespecified stopping rules. Eligibility requires confirmed non‑squamous NSCLC, appropriate pathologic staging, and documented uncommon EGFR alterations by a validated NGS or PCR assay, and completion of adjuvant chemotherapy if given. The study will monitor safety and efficacy outcomes related to recurrence and treatment tolerability over the follow‑up period.

Who should consider this trial

Good fit: Adults (≥18 years, ≥20 in Japan/Taiwan) with completely resected non‑squamous NSCLC staged IB–IIIB (T3N2M0 only) who have documented uncommon EGFR mutations (exon 20 insertions, PACC, or classical‑like mutations) and have recovered from surgery and completed any planned adjuvant chemotherapy are ideal candidates.

Not a fit: Patients with squamous histology, metastatic disease, incomplete (non‑R0) resections, or tumors lacking the specified uncommon EGFR mutations are unlikely to benefit from this adjuvant therapy.

Why it matters

Potential benefit: If effective, firmonertinib could lower the risk of cancer coming back after surgery for patients with these uncommon EGFR‑mutant tumors.

How similar studies have performed: Adjuvant EGFR inhibitors have shown clear benefit for common EGFR mutations (for example, osimertinib in ADAURA), but using firmonertinib specifically for uncommon EGFR mutations is a relatively novel approach that has not yet been proven in large adjuvant trials.

Eligibility criteria

Inclusion Criteria:

1. Sign the Informed Consent Form (ICF).
2. Aged ≥ 18 years old. Participants from Japan/Taiwan aged ≥ 20 years old.
3. Histologically confirmed diagnosis of primary non-small cell lung cancer (NSCLC) of predominantly non-squamous histology.
4. Underwent complete surgical resection of primary lung cancer and systematic lymph node dissection (R0 resection).
5. Classified post-operatively as Stage IB, II, IIIA, or IIIB (T3N2M0 only) on the basis of pathologic criteria, with the disease staging following the 9th Edition TNM Staging Classification: Lung Cancer issued by Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC).
6. Documented results of the presence of uncommon EGFR mutations (exon 20 insertion mutations, PACC mutations, and/or classical-like mutations, either as single mutations or as co-mutations), in tumor tissue or blood via a validated NGS or validated PCR assay.

Exclusion Criteria:

A participant would be excluded from the study if he/she meets any of the following:

1. NSCLC with EGFR Exon 19 deletion or L858R or C797S mutation.
2. Incomplete resection (R1/R2) or segmentectomy or wedge resection only.
3. Prior treatment with any of the following:

   1. Prior treatment with any antineoplastic therapy other than standard platinum-based doublet adjuvant chemotherapy.
   2. prior treatment with neoadjuvant therapy.
4. Concurrent malignant tumors other than the primary tumor; participants with cancers that can be treated locally and cured may be eligible.
5. Previous ILD (including drug-induced ILD) or active ILD/active radiation pneumonitis.

Where this trial is running

Beijing, Beijing Municipality and 1 other locations

• Peking University People's Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• Sun Yat-sen University Cancer Center — Guangdong, Guangzhou, China (RECRUITING)

Study contacts

• Principal investigator: Li Zhang, Master — Sun Yat-sen University
• Study coordinator: Li Zhang, Master

Conditions: NSCLC, Adjuvant Treatment, EGFR, Firmonertinib