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

March 21, 2024 updated by: ArriVent BioPharma, Inc.

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

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).

Study Overview

Study Type

Interventional

Enrollment (Estimated)

170

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • New South Wales
      • Blacktown, New South Wales, Australia, 2148
      • St Leonards, New South Wales, Australia, 2065
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
    • Anhui
    • Beijing
      • Beijing, Beijing, China, 101119
      • Chaoyang, Beijing, China, 100021
      • Haidan, Beijing, China, 100142
    • Chongqing
      • Chongqing, Chongqing, China, 400030
    • Guizhou
      • Guiyang, Guizhou, China, 550004
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
    • Henan
      • Zhengzhou, Henan, China, 450052
      • Zhengzhou, Henan, China, 450003
    • Hubei
      • Wuhan, Hubei, China, 430022
    • Jiangsu
      • XuZhou, Jiangsu, China, 221000
    • Jianxi
      • Nanchang, Jianxi, China, 330008
        • Recruiting
        • Allist Investigative Site
        • Contact:
          • Allist i Site
    • Jilin
      • Changchun, Jilin, China, 130012
    • Shan Dong
      • Jinan, Shan Dong, China, 250021
    • Shandong
      • Jinan, Shandong, China, 250117
    • Shanghai
      • Shanghai, Shanghai, China, 200030
    • Shanxi
      • Taiyuan, Shanxi, China, 030013
    • Chiba
    • Osaka
      • Ōsaka-sayama, Osaka, Japan, 589-8511
    • Tokyo
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1066 CX
    • California
      • Sacramento, California, United States, 95817
    • Florida
      • Celebration, Florida, United States, 34747
    • Michigan
      • Detroit, Michigan, United States, 48202
    • Texas
      • Houston, Texas, United States, 77030
    • Virginia
      • Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Stage 2 Expansion Cohort 1
Previously Treated NSCLC Patients with EGFR Exon 20 Insertion Mutations
Furmonertinib tablet
Other Names:
  • AST2818
Experimental: Stage 2 Expansion Cohort 2
Previously treated NSCLC Patients with HER2 Exon 20 Insertion Mutations
Furmonertinib tablet
Other Names:
  • AST2818
Experimental: Stage 1 Dose Escalation and Backfill
Experimental: Previously treated patients with advanced or metastatic NSCLC with activating EGFR or HER2 mutations
Furmonertinib tablet
Other Names:
  • AST2818
Experimental: Stage 2 Expansion Cohort 3
Previously treated NSCLC Patients with EGFR Activating Mutations, who are not eligible for Cohorts 1 and 4
Furmonertinib tablet
Other Names:
  • AST2818
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
Furmonertinib tablet
Other Names:
  • AST2818

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Up to 36 months after first dose
Stage 2: Overall Response Rate (ORR)
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose

Secondary Outcome Measures

Outcome Measure
Time Frame
Stage 1: Overall Response Rate
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 1: Duration of Response (DOR)
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 1: Disease Control Rate
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 1: Progression Free Survival
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 1: Depth of Response
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 1: Overall survival
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 1: Central Nervous System ORR
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 1: Central Nervous System DOR
Time Frame: Up to 36 months after first dose
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
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
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
Up to 36 months after first dose
Stage 2, all cohorts: Duration of Response
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 2, all cohorts: Disease Control Rate
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 2, all cohorts: Progression Free Survival
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 2, all cohorts: Depth of Response
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 2, all cohorts: Overall survival
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 2, all cohorts: Central Nervous System ORR
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 2, all cohorts: Central Nervous System DOR
Time Frame: Up to 36 months after first dose
Up to 36 months after first dose
Stage 2, Cohort 4 only: Overall Response Rate
Time Frame: Up to 36 months after first dose
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
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
Up to 36 months after first dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Morgan Lam, ArriVent BioPharma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2022

Primary Completion (Estimated)

September 1, 2025

Study Completion (Estimated)

September 1, 2025

Study Registration Dates

First Submitted

April 6, 2022

First Submitted That Met QC Criteria

May 3, 2022

First Posted (Actual)

May 6, 2022

Study Record Updates

Last Update Posted (Actual)

March 22, 2024

Last Update Submitted That Met QC Criteria

March 21, 2024

Last Verified

March 1, 2024

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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