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

• ClinicalTrials.gov Identifier: NCT05364073
• Recruitment Status: Recruiting
• First Posted: May 6, 2022
• Last Update Posted: April 19, 2024
• Sponsor: ArriVent BioPharma, Inc.
• Information provided by (Responsible Party): ArriVent BioPharma, Inc.

Tracking Information

• First Submitted Date: April 6, 2022
• First Posted Date: May 6, 2022
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: June 30, 2022
• Estimated Primary Completion Date: September 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 10, 2022)

• 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 ]

• Original Primary Outcome Measures (submitted: May 3, 2022): 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 ]

Current Secondary Outcome Measures (submitted: November 10, 2022)

• Stage 1: Overall Response Rate [ Time Frame: Up to 36 months after first dose ]
• Stage 1: Duration of Response (DOR) [ Time Frame: Up to 36 months after first dose ]
• Stage 1: Disease Control Rate [ Time Frame: Up to 36 months after first dose ]
• Stage 1: Progression Free Survival [ Time Frame: Up to 36 months after first dose ]
• Stage 1: Depth of Response [ Time Frame: Up to 36 months after first dose ]
• Stage 1: Overall survival [ Time Frame: Up to 36 months after first dose ]
• Stage 1: Central Nervous System ORR [ Time Frame: Up to 36 months after first dose ]
• Stage 1: Central Nervous System DOR [ Time Frame: Up to 36 months after first dose ]
• Stage 1: Plasma concentrations of furmonertinib and its major metabolite (AST5902) [ Time Frame: Up to 36 months after first dose ]
• Stage 1, Cohort 1, Backfill only: Plasma concentrations of furmonertinib and its major metabolite (AST5902) [ Time Frame: Up to 36 months after first dose ]
• Stage 1, Cohort 1, Backfill only: Plasma concentrations of midazolam and its metabolite (1-OH-midazolam) [ Time Frame: Up to 36 months after first dose ]
• Stage 2, all cohorts: Duration of Response [ Time Frame: Up to 36 months after first dose ]
• Stage 2, all cohorts: Disease Control Rate [ Time Frame: Up to 36 months after first dose ]
• Stage 2, all cohorts: Progression Free Survival [ Time Frame: Up to 36 months after first dose ]
• Stage 2, all cohorts: Depth of Response [ Time Frame: Up to 36 months after first dose ]
• Stage 2, all cohorts: Overall survival [ Time Frame: Up to 36 months after first dose ]
• Stage 2, all cohorts: Central Nervous System ORR [ Time Frame: Up to 36 months after first dose ]
• Stage 2, all cohorts: Central Nervous System DOR [ Time Frame: Up to 36 months after first dose ]
• Stage 2, Cohort 4 only: Overall Response Rate [ Time Frame: Up to 36 months after first dose ]
• Stage 2, all cohorts: Number of incidence and severity of AEs as a measure of safety and tolerability of Furmonertinib [ Time Frame: Up to 36 months after first dose ]
• Stage 2, all cohorts: Plasma concentrations of furmonertinib and its major metabolite (AST5902) [ Time Frame: Up to 36 months after first dose ]

Original Secondary Outcome Measures (submitted: May 3, 2022)

• Overall Response Rate (ORR) [ Time Frame: Up to 36 months after first dose ]
• Duration of Response (DOR) [ Time Frame: Up to 36 months after first dose ]
• Progression Free Survival (PFS) [ Time Frame: Up to 36 months after first dose ]
• Overall survival [ Time Frame: Up to 36 months after first dose ]
• Central Nervous System (CNS) ORR [ Time Frame: Up to 36 months after first dose ]
• Central Nervous System (CNS) DOR [ Time Frame: Up to 36 months after first dose ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Phase 1b Dose Escalation and Dose Expansion Study Evaluating the Safety, Pharmacokinetics, and Antitumor Activity of Furmonertinib in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Activating Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Mutations
• Brief Summary: This is a Phase 1b, open-label, multi-center, dose-escalation and dose expansion study designed to evaluate the safety, pharmacokinetics (PK), and preliminary antitumor activity 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. Patients will be enrolled into one of 2 stages: Stage 1 (Dose Escalation and Backfill Cohorts) and Stage 2 (Dose Expansion).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Small Cell Lung Cancer (NSCLC)
• Metastatic Non-Small Cell Lung Cancer
• Advanced Non-Small Cell Lung Cancer
• HER2 Exon 20 Mutations
• EGFR Exon 20 Mutations
• EGFR Uncommon Mutations, Including G719X and S768I

Intervention

Drug: Furmonertinib

Furmonertinib tablet

Other Name: AST2818

Study Arms

• Experimental: Stage 1 Dose Escalation and Backfill
  Experimental: Previously treated patients with advanced or metastatic NSCLC with activating EGFR or HER2 mutations
  Intervention: Drug: Furmonertinib
• Experimental: Stage 2 Expansion Cohort 1
  Previously Treated NSCLC Patients with EGFR Exon 20 Insertion Mutations
  Intervention: Drug: Furmonertinib
• Experimental: Stage 2 Expansion Cohort 2
  Previously treated NSCLC Patients with HER2 Exon 20 Insertion Mutations
  Intervention: Drug: Furmonertinib
• Experimental: Stage 2 Expansion Cohort 3
  Previously treated NSCLC Patients with EGFR Activating Mutations, who are not eligible for Cohorts 1 and 4
  Intervention: Drug: Furmonertinib
• Experimental: Stage 2 Expansion Cohort 4
  Untreated or Previously treated EGFR TKI Naïve NSCLC Patients with EGFR Uncommon Mutations, excluding EGFR exon 20 insertion mutations
  Intervention: Drug: Furmonertinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 10, 2022): 170
• Original Estimated Enrollment (submitted: May 3, 2022): 108
• Estimated Study Completion Date: September 2025
• Estimated Primary Completion Date: September 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Histologically or cytologically documented, locally advanced or metastatic Non-Small Cell Lung Cancer (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 or intolerable; 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 Epidermal Growth Factor Receptor (EGFR) mutations sensitive to osimertinib, the patient must have received osimertinib prior to study enrollment in regions where osimertinib is approved, including the US.

Stage 1 dose escalation and backfill cohorts and Stage 2 Cohorts 1, 2, 3 and 4:

-Patients with CNS metastases (including leptomeningeal disease) may be eligible if meeting additional protocol specified 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 Mutations, who are not eligible for Cohorts 1 and 4 Inclusion Criteria

• 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.
• The patient must have experienced disease progression or have intolerance to treatment with the standard of care EGFR TKI.
• Patients with CNS metastases may be eligible if meeting additional protocol specified criteria.

Stage 2 Cohort 4 Untreated or Previously Treated EGFR TKI-Naïve, 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 a. 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

Key Exclusion Criteria:

• Treatment with chemotherapy, targeted therapy, biologic therapy or an investigational agent as anti-cancer therapy within 3 or 3 elimination weeks or five half-lives prior to initiation of furmonertinib, whichever is shorter, or endocrine therapy within 2 weeks prior to initiation of furmonertinib.
• 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.
• AE 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-Naïve, Locally Advanced or Metastatic NSCLC Patients with EGFR Uncommon 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Nichole Baio; 628-277-4836; FURMO002CT@arrivent.com

• Listed Location Countries: Australia, Canada, China, France, Italy, Japan, Korea, Republic of, Netherlands, Spain, United Kingdom, United States
• Removed Location Countries: Mexico

Administrative Information

• NCT Number: NCT05364073
• Other Study ID Numbers: FURMO-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: ArriVent BioPharma, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ArriVent BioPharma, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Morgan Lam; ArriVent BioPharma

• PRS Account: ArriVent BioPharma, Inc.
• Verification Date: April 2024