Study of Furmonertinib in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With Activating EGFR or HER2 Mutations, Including Exon 20 Insertion Mutations

Sponsor

ArriVent BioPharma, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05364073

Collaborator

(none)

108

Enrollment

Locations

Arms

38.1

Anticipated Duration (Months)

8.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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 NSCLC with activating EGFR or HER2 mutations, including Exon 20 insertion mutations. Patients will be enrolled into 2 stages: Stage 1 (Dose Escalation and Backfill Cohorts) and Stage 2 (Dose Expansion).

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer Carcinoma, Non-Small-Cell Lung Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Protein Kinase Inhibitors	Drug: Furmonertinib Drug: Furmonertinib Drug: Furmonertinib Drug: Furmonertinib	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 With Activating EGFR or HER2 Mutations, Including Exon 20 Insertion Mutations

Actual Study Start Date :

Jun 30, 2022

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stage 1 Dose Escalation and Backfill Previously treated patients with advanced or metastatic NSCLC with activating EGFR or HER2 mutations, including Exon 20 insertion mutations	Drug: Furmonertinib Furmonertinib tablet Other Names: AST2818
Experimental: Stage 2 Expansion Cohort 1 Previously Treated NSCLC Patients with EGFR Exon 20 Insertion Mutations	Drug: Furmonertinib Furmonertinib tablet Other Names: AST2818
Experimental: Stage 2 Expansion Cohort 2 Previously treated NSCLC Patients with HER2 Exon 20 Insertion Mutations	Drug: Furmonertinib Furmonertinib tablet Other Names: AST2818
Experimental: Stage 2 Expansion Cohort 3 Previously treated NSCLC Patients with EGFR Activating Mutations	Drug: Furmonertinib Furmonertinib tablet Other Names: AST2818

Outcome Measures

Primary Outcome Measures

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]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 or intolerable; or for whom a clinical trial of an investigational agent is a recognized standard of care.
Patients with a history of treated CNS metastases or new asymptomatic CNS metastases detected at screening are eligible.
Documented radiologic disease progression during or after the last systemic anti-cancer therapy before the first dose of the investigational product (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 US.

Stage 1 Dose Escalation and Backfill Cohorts Inclusion Criteria:

Documented validated results from local testing of blood or tumor tissue confirming the presence of an EGFR Exon 20 insertion mutation, HER2 Exon 20 insertion mutation, or EGFR activating mutation.
For patients with NSCLC with EGFR Exon 20 insertion mutations or HER2 Exon 20 insertion mutations, the patient must have experienced disease progression or have intolerance to treatment with platinum-based chemotherapy.
For patients with NSCLC with EGFR activating mutations other than Exon 20 insertion mutations, the patient must have experienced disease progression with the standard of care EGFR TKI.

Stage 2 Cohort 1 (Previously Treated NSCLC Patients with EGFR Exon 20 Insertion Mutations) Inclusion Criteria

Documented validated results from either local testing of blood or tumor tissue confirming the presence of EGFR Exon 20 insertion mutations.
The patient must have experienced disease progression or have intolerance to treatment with platinum-based chemotherapy.

Stage 2 Cohort 2 (Previously treated NSCLC Patients with HER2 Exon 20 Insertion Mutations) Inclusion Criteria

Documented validated results from either local testing of blood or tumor tissue confirming the presence of HER2 Exon 20 insertion mutations.
The patient must have experienced disease progression or have intolerance to treatment with platinum-based chemotherapy.

Stage 2 Cohort 3 (Previously Treated NSCLC Patients with EGFR Activating Mutations and Excluding Exon 20 Insertion Mutations) Inclusion Criteria

Documented validated results from either local testing of blood or tumor tissue confirming the presence of an EGFR activating mutation.
The patient must have experienced disease progression or have intolerance to treatment with the standard of care EGFR TKI.

Key Exclusion Criteria:

Treatment with chemotherapy, immunotherapy, biologic therapy or an investigational agent as anti-cancer therapy within 3 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 bony metastases within 2 weeks prior to initiation of furmonertinib.
Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1 except for alopecia or Grade ≤ 2 peripheral neuropathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ArriVent Investigative Site	Glendale	California	United States	91204
2	ArriVent Investigative Site	Sacramento	California	United States	95817
3	ArriVent Investigative Site	Orlando	Florida	United States	32804
4	ArriVent Investigative Site	Westwood	Kansas	United States	66205
5	ArriVent Investigative Site	Detroit	Michigan	United States	48202
6	ArriVent Investigative Site	Fairfax	Virginia	United States	22031
7	ArriVent Investigative Site	Blacktown	New South Wales	Australia	2148
8	ArriVent Investigative Site	Heidelberg	Victoria	Australia	3084
9	ArriVent Investigative Site	Chiba-Shi		Japan	260-0013
10	ArriVent Investigative Site	Madrid		Spain	28033
11	ArriVent Investigative Site	Madrid		Spain	28050
12	ArriVent Investigative Site	Valencia		Spain	46026
13	ArriVent Investigative Site	London		United Kingdom	NW12PG