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

Non-Small Cell Lung Cancer (NSCLC) Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05364073
• Other study ID #: FURMO-002
• Status: Recruiting
• Phase: Phase 1
• Start date: June 30, 2022
• Est. completion date: September 2025

Study information

• Verified date: June 2024
• Source: ArriVent BioPharma, Inc.
• Contact: Nichole Baio
• Phone: 628-277-4836
• Email: FURMO002CT[@]arrivent.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Non-Small Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Non-Small Cell Lung Cancer
• Non-Small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• Furmonertinib
Furmonertinib tablet
• Furmonertinib
Furmonertinib tablet
• Furmonertinib
Furmonertinib tablet
• Furmonertinib
Furmonertinib tablet
• Furmonertinib
Furmonertinib tablet

Locations

Country	Name	City	State
Australia	ArriVent Investigative Site	Blacktown	New South Wales
Australia	ArriVent Investigative Site	Heidelberg	Victoria
Australia	ArriVent Investigative Site	St Leonards	New South Wales
Canada	Arrivent Investigative Site	Edmonton
Canada	Arrivent Investigative Site	Toronto
China	Allist Investigative Site	Beijing	Beijing
China	Allist Investigative Site	Changchun	Jilin
China	Allist Investigative Site	Chaoyang	Beijing
China	Allist Investigative Site	Chongqing	Chongqing
China	Allist Investigative Site	Guiyang	Guizhou
China	Allist Investigative Site	Harbin	Heilongjiang
China	Allist Investigative Site	Hefei	Anhui
China	Allist Investigative Site	Jinan	Shan Dong
China	Allist Investigative Site	Jinan	Shandong
China	Allist Investigative Site	Nanchang	Jianxi
China	Allist Investigative Site	Shanghai	Shanghai
China	Allist Investigative Site	Taiyuan	Shanxi
China	Allist Investigative Site	Wuhan	Hubei
China	Allist Investigative Site	XuZhou	Jiangsu
China	Allist Investigative Site	Zhengzhou	Henan
China	Allist Investigative Site	Zhengzhou	Henan
France	ArriVent Investigative Site	Lyon
France	Arrivent Investigative Site	Toulouse
France	Arrivent Investigative Site	Villejuif
Italy	ArriVent Investigative Site	Medolla
Japan	ArriVent Investigative Site	Chiba-Shi	Chiba
Japan	Arrivent Investigative Site	Chuo	Tokyo
Japan	Arrivent Investigative Site	Koto-Ku	Tokyo
Japan	Arrivent Investigative Site	Osaka-sayama	Osaka
Korea, Republic of	Arrivent Investigative Site	Gwangju
Korea, Republic of	Arrivent Investigative Site	Seoul
Netherlands	Arrivent Investigative Site	Amsterdam	Noord-Holland
Spain	ArriVent Investigative Site	Barcelona
Spain	ArriVent Investigative Site	Madrid
Spain	ArriVent Investigative Site	Madrid
Spain	ArriVent Investigative Site	Valencia
United Kingdom	ArriVent Investigative Site	London
United States	ArriVent Investigative Site	Celebration	Florida
United States	ArriVent Investigative Site	Detroit	Michigan
United States	ArriVent Investigative Site	Fairfax	Virginia
United States	ArriVent Investigative Site	Houston	Texas
United States	ArriVent Investigative Site	Prescott	Arizona
United States	ArriVent Investigative Site	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
ArriVent BioPharma, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  France,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  United Kingdom, 

Outcome

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