Efficacy and Safety of Furmonertinib in Patients With Locally Advanced or Metastatic NSCLC With EGFR Exon 20 Insertion

A Phase 2, Multicenter, Open-Label Study to Assess the Efficacy and Safety of Furmonertinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations

This is a Phase 2, Multicenter, Open-Label Study to Assess the Efficacy and Safety of Furmonertinib in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations.

The study plans to enroll approximately 100 patients from approximately 70 sites. Patients are locally advanced or metastatic NSCLC with EGFR exon 20 insertions who have progressed during or after platinum-based chemotherapy. Furmonertinib Mesilate will be treated 240 mg QD until disease progression or unacceptable toxicity.

Primary endpoint is ORR. Secondary endpoints include DOR, DCR, DepOR, PFS, OS, CNS ORR, CNS DOR, CNS PFS, safety and the PK profile of Furmonertinib Mesilate and its metabolites (AST5902).

Inclusion Criteria:

• Age ≥ 18 years at time of signing Informed Consent Form
• Histologically or cytologically documented, locally advanced or metastatic NSCLC not amenable to curative surgery or radiotherapy
• Documented validated results from local or central testing (as designated by the Sponsor) of blood or tumor tissue confirming the presence of an EGFR exon 20 insertion mutation
• Documented radiologic progression on or after prior platinum-based chemotherapy (with or without anti-PD1/PD-L1 agents) in the locally advanced or metastatic setting
• Documented radiologic disease progression during or after the last systemic anticancer therapy before the first dose of furmonertinib
• Measurable disease per RECIST v1.1
• ECOG performance status of 0 or 1
• Life expectancy of ≥ 12 weeks
• Patients with CNS metastases are eligible, provided they meet all of the following criteria: Measurable disease outside the CNS; No ongoing requirement for corticosteroids as therapy for CNS metastases, with corticosteroids discontinued for ≥ 2 weeks prior to enrollment; No ongoing symptoms attributed to CNS metastases; No active CNS metastases or spinal cord compression (i.e., progressing or requiring anticonvulsants or corticosteroids for symptomatic control); No evidence of interim CNS disease progression between the completion of CNS-directed therapy and the screening radiographic study; Time since whole brain radiation therapy (WBRT) is ≥ 21 days prior to first dose of study treatment, time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of study treatment, or time since surgical resection is ≥ 28 days
• Adequate hematologic and organ function within 14 days prior to initiation of study treatment
• For women of childbearing potential or men who are not surgically sterile: Agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs or sperm

Exclusion Criteria:

• Prior treatment with any EGFR-targeting agents (e.g., EGFR tyrosine kinase inhibitors [TKIs], monoclonal antibodies, or bispecific antibodies).
• More than 3 prior systemic anticancer therapy regimens for locally advanced or metastatic NSCLC
• Inability or unwillingness to swallow pills
• Severe acute or chronic infections
• Previous interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid therapy; or having the clinical manifestations of suspected ILD
• History of or active clinically significant cardiovascular dysfunction
• Mean resting corrected QT interval (QTc) > 470 msec, obtained from triplicate ECGs, using the screening clinic ECG machine derived Fridericia's formula (QTcF) value
• Clinically significant prolonged QT interval or other arrhythmia or clinical status considered by investigators that may increase the risk of prolonged QT interval (e.g., complete left bundle branch block, degree III atrioventricular block, second-degree heart block, PR interval > 250 msec, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives, serious hypokalemia, heart failure) or current use of the drugs that may lead to prolonged QT interval.
• AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for alopecia, vitiligo, endocrinopathy managed with replacement therapy, or Grade ≤ 2 peripheral neuropathy.