Clinical trial NCT05364073: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: 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
Keywords: Non-small cell lung cancer (NSCLC)
Metastatic Non-Small Cell Lung Cancer
Advanced Non-Small Cell Lung Cancer
EGFR
HER2
Exon 20 Insertion Mutations
HER2 kinase domain mutations
Epidermal Growth Factor Receptor (EGFR) kinase domain mutations
Exon 20
Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations
HER2 Exon 20 Insertion Mutations
Tyrosine Kinase Inhibitor (TKI)
Human Epidermal Growth Factor Receptor 2 (HER2)
Epidermal Growth Factor Receptor (EGFR)
EGFR uncommon mutations
EGFR atypical mutations
EGFR rare mutations
V774M
G719X
S768I
E709X
R776C/H
G724S
E736K
I740_K745dup
N771G
K757M/R
V769L/M
T854X
T751_I759delinsN
G719A
G719S
R776C
R776H
K757M
K757R
V769L
V769M
osimertinib
afatinib
E709_T710del insD
G779F
L747X
Lead sponsor: ArriVent BioPharma, Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-06
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Stage 1: Number of incidence and severity of adverse events (AEs) as a measure of safety and tolerability of Furmonertinib
timeFrame: Up to 36 months after first dose
measure: Stage 2: Overall Response Rate (ORR)
timeFrame: Up to 36 months after first dose
Secondary outcomes:
measure: Stage 1: Overall Response Rate
timeFrame: Up to 36 months after first dose
measure: Stage 1: Duration of Response (DOR)
timeFrame: Up to 36 months after first dose
measure: Stage 1: Disease Control Rate
timeFrame: Up to 36 months after first dose
measure: Stage 1: Progression Free Survival
timeFrame: Up to 36 months after first dose
measure: Stage 1: Depth of Response
timeFrame: Up to 36 months after first dose
measure: Stage 1: Overall survival
timeFrame: Up to 36 months after first dose
measure: Stage 1: Central Nervous System ORR
timeFrame: Up to 36 months after first dose
measure: Stage 1: Central Nervous System DOR
timeFrame: Up to 36 months after first dose
measure: Stage 1: Plasma concentrations of furmonertinib and its major metabolite (AST5902)
timeFrame: Up to 36 months after first dose
measure: Stage 1, Cohort 1, Backfill only: Plasma concentrations of furmonertinib and its major metabolite (AST5902)
timeFrame: Up to 36 months after first dose
measure: Stage 1, Cohort 1, Backfill only: Plasma concentrations of midazolam and its metabolite (1-OH-midazolam)
timeFrame: Up to 36 months after first dose
measure: Stage 2, all cohorts: Duration of Response
timeFrame: Up to 36 months after first dose
measure: Stage 2, all cohorts: Disease Control Rate
timeFrame: Up to 36 months after first dose
measure: Stage 2, all cohorts: Progression Free Survival
timeFrame: Up to 36 months after first dose
measure: Stage 2, all cohorts: Depth of Response
timeFrame: Up to 36 months after first dose
measure: Stage 2, all cohorts: Overall survival
timeFrame: Up to 36 months after first dose
measure: Stage 2, all cohorts: Central Nervous System ORR
timeFrame: Up to 36 months after first dose
measure: Stage 2, all cohorts: Central Nervous System DOR
timeFrame: Up to 36 months after first dose
measure: Stage 2, Cohort 4 only: Overall Response Rate
timeFrame: Up to 36 months after first dose
measure: Stage 2, all cohorts: Number of incidence and severity of AEs as a measure of safety and tolerability of Furmonertinib
timeFrame: Up to 36 months after first dose
measure: Stage 2, all cohorts: Plasma concentrations of furmonertinib and its major metabolite (AST5902)
timeFrame: Up to 36 months after first dose
Other outcomes:
Locations:
city: Prescott
country: United States
facility: ArriVent Investigative Site
state: Arizona
city: Sacramento
country: United States
facility: ArriVent Investigative Site
state: California
city: Whittier
country: United States
facility: ArriVent Investigative Site
state: California
city: Celebration
country: United States
facility: ArriVent Investigative Site
state: Florida
city: Detroit
country: United States
facility: ArriVent Investigative Site
state: Michigan
city: Houston
country: United States
facility: ArriVent Investigative Site
state: Texas
city: Fairfax
country: United States
facility: ArriVent Investigative Site
state: Virginia
city: Blacktown
country: Australia
facility: ArriVent Investigative Site
state: New South Wales
city: St Leonards
country: Australia
facility: ArriVent Investigative Site
state: New South Wales
city: Heidelberg
country: Australia
facility: ArriVent Investigative Site
state: Victoria
city: Edmonton
country: Canada
facility: Arrivent Investigative Site
city: Toronto
country: Canada
facility: Arrivent Investigative Site
city: Hefei
country: China
facility: Allist Investigative Site
state: Anhui
city: Beijing
country: China
facility: Allist Investigative Site
state: Beijing
city: Chaoyang
country: China
facility: Allist Investigative Site
state: Beijing
city: Chongqing
country: China
facility: Allist Investigative Site
state: Chongqing
city: Harbin
country: China
facility: Allist Investigative Site
state: Heilongjiang
city: Zhengzhou
country: China
facility: Allist Investigative Site
state: Henan
city: Zhengzhou
country: China
facility: Allist Investigative Site
state: Henan
city: Wuhan
country: China
facility: Allist Investigative Site
state: Hubei
city: XuZhou
country: China
facility: Allist Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Allist Investigative Site
state: Jianxi
city: Changchun
country: China
facility: Allist Investigative Site
state: Jilin
city: Jinan
country: China
facility: Allist Investigative Site
state: Shan Dong
city: Jinan
country: China
facility: Allist Investigative Site
state: Shandong
city: Taiyuan
country: China
facility: Allist Investigative Site
state: Shanxi
city: Lyon
country: France
facility: ArriVent Investigative Site
city: Toulouse
country: France
facility: Arrivent Investigative Site
city: Villejuif
country: France
facility: Arrivent Investigative Site
city: Medolla
country: Italy
facility: ArriVent Investigative Site
city: Chiba-Shi
country: Japan
facility: ArriVent Investigative Site
state: Chiba
city: Ōsaka-sayama
country: Japan
facility: Arrivent Investigative Site
state: Osaka
city: Chuo
country: Japan
facility: Arrivent Investigative Site
state: Tokyo
city: Koto-Ku
country: Japan
facility: Arrivent Investigative Site
state: Tokyo
city: Gwangju
country: Korea, Republic of
facility: Arrivent Investigative Site
city: Seoul
country: Korea, Republic of
facility: Arrivent Investigative Site
city: Amsterdam
country: Netherlands
facility: Arrivent Investigative Site
state: Noord-Holland
city: Barcelona
country: Spain
facility: ArriVent Investigative Site
city: Madrid
country: Spain
facility: ArriVent Investigative Site
city: Madrid
country: Spain
facility: ArriVent Investigative Site
city: Valencia
country: Spain
facility: ArriVent Investigative Site
city: London
country: United Kingdom
facility: ArriVent Investigative Site
Study officials:
affiliation: ArriVent BioPharma
name: Morgan Lam
role: STUDY_DIRECTOR
References: