A Study of Furmonertinib in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Activating, Including Uncommon, Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Mutations

JRCT ID: jRCT2031220455

Registered date:22/11/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Non-small cell lung cancer harboring activating EGFR or HER2 kinase domain mutations
• Date of first enrollment: 21/12/2022
• Target sample size: 15
• Countries of recruitment: Australia,Japan,China,Japan,US,Japan,UK,Japan,Spain,Japan,Canada,Japan,France,Japan,Korea,Japan,Netherlands,Japan,Italy,Japan
• Study type: Interventional

Intervention(s)

Furmonertinib will be administered once per day orally on an empty stomach at about the same time each day.
Stage 1 (Dose Escalation):
Dose escalation will begin with Stage 1, Cohort 1, in which furmonertinib will be administered at 240 mg by mouth (PO) QD for 21-day cycles. The maximum dose to be evaluated in this study will be 240 mg PO QD. Patients will be evaluated for DLTs to determine the expansion dose for furmonertinib in Stage 2.
Stage 2 (Dose Expansion):
Stage 2 will comprise 4 cohorts (Stage 2 Cohort 1, 2, 3 and 4).
Based upon the existing preliminary safety and efficacy data, and pending clearance of dose escalation at the 240-mg dose level during Stage 1, the targeted expansion dose is 240 mg for Stage 2 Cohorts 1, 2, and 3, and 160 mg and 240 mg for Stage 2, Cohort 4.

Outcome(s)

Primary Outcome

Stage 1: Number of incidence and severity of adverse events (AEs) as a measure of safety and tolerability of Furmonertinib [Time Frame: Up to 36 months after first dose]
Stage 2: Overall Response Rate (ORR) [ Time Frame: Up to 36 months after first dose]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Key Inclusion Criteria:
- Histologically or cytologically documented, locally advanced or metastatic NSCLC not amenable to curative surgery or radiotherapy
- Disease that has progressed after at least one available standard therapy; or for whom standard therapy has proven to be ineffective, intolerable, or considered inappropriate, or for whom a clinical trial of an investigational agent is a recognized standard of care.
- Documented radiologic disease progression during or after the last systemic anti-cancer therapy before the first dose of furmonertinib.
- For patients with EGFR mutations sensitive to osimertinib, the patient must have received osimertinib prior to study enrollment in regions where osimertinib is approved, including the United States (US).

Stage 1 dose escalation and backfill cohorts and Stage 2 Cohorts 1, 2, 3, and 4
- Patients with CNS metastases (including leptomeningeal disease) are eligible, provided they meet the criteria.

Stage 1 Dose Escalation and Backfill Cohorts Inclusion Criteria
- Documented validated results from local testing of tumor tissue or blood confirming the presence of an activating, including uncommon, EGFR mutation or HER2 exon 20 insertion mutation performed at a CLIA-or equivalently certified laboratory.

Stage 2 Cohort 1 Previously Treated, Locally Advanced or Metastatic NSCLC Patients with EGFR exon 20 Insertion Mutations Inclusion Criteria
- Documented validated results from local testing of either tumor tissue or blood confirming the presence of EGFR exon 20 insertion mutations, performed at a CLIA- or equivalently certified laboratory
- The patient must have experienced disease progression or have intolerance to treatment with platinum-based chemotherapy.

Stage 2 Cohort 2 Previously treated, Locally Advanced or Metastatic NSCLC Patients with HER2 exon 20 Insertion Mutations Inclusion Criteria
- Documented validated results from local testing of either tumor tissue or blood confirming the presence of HER2 exon 20 insertion mutations, performed at a CLIA- or equivalently certified laboratory.
- The patient must have experienced disease progression or have intolerance to treatment with platinum-based chemotherapy
- In regions in which fam-trastuzumab deruxtecan-nxki is approved and available for adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 exon 20 mutations, the patient must have received or be considered not appropriate to receive fam-trastuzumab deruxtecan-nxki.

Stage 2 Cohort 3 Previously Treated, Locally Advanced or Metastatic NSCLC Patients with EGFR Activating Mutations
- Documented validated results from local testing of either tumor tissue or blood confirming the presence of an EGFR activating mutation, performed at a CLIA- or equivalently certified laboratory.
- Patients with CNS metastases may be eligible if meeting additional protocol specified criteria.

Stage 2 Cohort 4 Untreated or Previously Treated EGFR-TKI-Naive, Locally Advanced or Metastatic NSCLC Patients with EGFR Uncommon Mutations Excluding EGFR Exon 20 Insertions Inclusion Criteria.
- Previously untreated in the locally advanced or metastatic setting or have progressed after at least 1 available standard therapy, or for whom standard therapy has proven to be ineffective, intolerable, or considered inappropriate
- Documented validated results from local testing of either tumor tissue or blood confirming the presence of an EGFR Uncommon mutation, performed at a CLIA- or equivalently certified laboratory.
- Representative mutations include, but are not limited to:
G719X, S768I, E709X, G779F, L747X, V774M, E709_T710delinsD, R776C/H, G724S, E736K, I740_K745dup, N771G, K757M/R, V769L/M, T854X, T751_I759delinsN

Exclude criteria

Key Exclusion Criteria
- Treatment with chemotherapy, targeted therapy, biologic therapy, or an investigational agent as anti-cancer therapy within 3 weeks or 5 elimination half-lives prior to initiation of furmonertinib, whichever is shorter.
- Radiation therapy as cancer therapy within 4 weeks prior to initiation of furmonertinib.
- Palliative radiation to bone metastases within 2 weeks prior to initiation of furmonertinib.
- AEs from prior anticancer therapy that have not resolved to Grade <= 1 except for alopecia or Grade <= 2 peripheral neuropathy.

Stage 2 Cohort 4 Untreated or Previously Treated EGFR-TKI-Naive, Locally Advanced or Metastatic NSCLC Patients with Uncommon EGFR Mutations Exclusion Criteria
- Prior treatment with any EGFR-TKIs
- Progression during neoadjuvant or adjuvant therapy (e.g., chemotherapy, radiotherapy, immunotherapy or investigational agents) or within 12 months of completion of above therapies

Related Information

• Primary Sponsor: Isui Ayako
• Secondary ID(s): 2021-005831-22,NCT05364073