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
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT05364073 |
Recruitment Status :
Recruiting
First Posted : May 6, 2022
Last Update Posted : April 19, 2024
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
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 | Drug: Furmonertinib | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 170 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 (NSCLC) With Activating Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Mutations |
Actual Study Start Date : | June 30, 2022 |
Estimated Primary Completion Date : | September 2025 |
Estimated Study Completion Date : | September 2025 |
Arm | Intervention/treatment |
---|---|
Experimental: Stage 1 Dose Escalation and Backfill
Experimental: Previously treated patients with advanced or metastatic NSCLC with activating EGFR or HER2 mutations
|
Drug: Furmonertinib
Furmonertinib tablet
Other Name: AST2818 |
Experimental: Stage 2 Expansion Cohort 1
Previously Treated NSCLC Patients with EGFR Exon 20 Insertion Mutations
|
Drug: Furmonertinib
Furmonertinib tablet
Other Name: AST2818 |
Experimental: Stage 2 Expansion Cohort 2
Previously treated NSCLC Patients with HER2 Exon 20 Insertion Mutations
|
Drug: Furmonertinib
Furmonertinib tablet
Other Name: AST2818 |
Experimental: Stage 2 Expansion Cohort 3
Previously treated NSCLC Patients with EGFR Activating Mutations, who are not eligible for Cohorts 1 and 4
|
Drug: Furmonertinib
Furmonertinib tablet
Other Name: 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
|
Drug: Furmonertinib
Furmonertinib tablet
Other Name: AST2818 |
- 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 ]
- 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 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05364073
Contact: Nichole Baio | 628-277-4836 | FURMO002CT@arrivent.com |
Study Director: | Morgan Lam | ArriVent BioPharma |
Responsible Party: | ArriVent BioPharma, Inc. |
ClinicalTrials.gov Identifier: | NCT05364073 |
Other Study ID Numbers: |
FURMO-002 |
First Posted: | May 6, 2022 Key Record Dates |
Last Update Posted: | April 19, 2024 |
Last Verified: | April 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases |
Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Aflutinib Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |