IN10018 Combination Therapy in Advanced EGFR Mutation-positive NSCLC

NCT05994131 | Recruiting Phase 1 DMC

• 1 other identifier: IN10018-014
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open-label, phase Ib/II clinical study to evaluate the safety, tolerability, pharmacokinetics and antitumor efficacy of IN10018 in combination with third-generation EGFR-TKI (Furmonertinib is the proposed) in previously-treated or naïve advanced EGFR-mutation positive NSCLC.

Conditions

NSCLC

Keywords

EGFR mutation-positve

Outcome Measures

Primary Outcomes (3)

• Recommended phase II dose (RP2D) of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced EGFR mutation-positive NSCLC.

  Evaluate the number of patients with dose-limited toxicities (DLTs); Determine the RP2D of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced NSCLC.

  3 years

• ORR of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced EGFR mutation-positive NSCLC.

  Defined as the proportion of subjects with complete response (CR) or partial response (PR)

  3 years

• Tumor Shrinkage Rate (TSR) of IN10018 in combination with third-generation EGFR-TKI in cohort 3 of advanced treatment-naive EGFR mutation-positive NSCLC.

  Defined as the percentage of subjects with the best shrinkage rate of target lesions ≥ 70% and simultaneously with a best response of partial response (PR) or complete response (CR).

  3 years

Secondary Outcomes (12)

• PFS of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.

  3 years

• DOR of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.

  3 years

• DCR of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.

  3 years

• OS of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.

  3 years

• Number of patients with adverse event

  3 years

Study Arms (2)

Experimental Group in cohort 1, cohort 2, and cohort 3

EXPERIMENTAL

IN10018+Furmonertinib

Drug: IN10018; Drug: Furmonertinib

Control Group in cohort 3

ACTIVE COMPARATOR

Furmonertinib

Drug: Furmonertinib

Interventions

IN10018 DRUG

orally taken once daily

Also known as: BI 853520

Experimental Group in cohort 1, cohort 2, and cohort 3

Furmonertinib DRUG

orally taken once daily

Control Group in cohort 3; Experimental Group in cohort 1, cohort 2, and cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to understand and be willing to sign informed consent.
• Male or female aged ≥ 18 years old at the time of signing informed consent.
• Histologically or cytologically confirmed locally advanced or metastatic NSCLC, who is not suitable for radical surgery or radiotherapy.
• Documented EGFR mutations known to be associated with EGFR-TKI sensitivity, including Ex19del or L858R. Except for EGFR-TKI sensitive mutation, coexisting with other EGFR mutation types such as T790M can be allowed.
• Prior systemic antitumor therapy allowed are listed as follows:
• Cohort 1: Subjects who are on the treatment of Furmonertinib as the first-line treatment setting.
• Cohort 2: Subjects failed in third-generation EGFR-TKI treatment and also failed in or were intolerant to 1-2 lines of chemotherapy.
• Cohort 3: subjects who haven't accepted any systemic therapy before. Prior adjuvant or neoadjuvant chemotherapy is permitted if an interval from the lost dose of adjuvant or neoadjuvant chemotherapy to the first documented PD is \>6 months.
• Measurable lesions at baseline according to RECIST 1.1 criteria.
• Has an ECOG performance status of 0 or 1.
• Estimated life expectancy is more than 3 months.
• Adequate bone marrow, liver, renal, and coagulation function within 7 days prior to the first dose of study treatment/randomization.

You may not qualify if:

• Have experienced major surgical procedures or major trauma within 28 days prior to the first dose of study treatment/randomization.
• Have received the following prior systemic antitumor therapy:
• Cohort 1: Have received chemotherapy, target therapy besides Furmonertinib, immunotherapy, biological therapy, and other antitumor drugs.
• Cohort 2: Have received chemotherapy, targeted therapy, immunotherapy, biological therapy, and other antitumor drugs within 28 days prior to the first dose of study treatment.
• Cohort 3: Have received systemic antitumor therapy for locally-advanced or metastatic NSCLC including chemotherapy, target therapy, immunotherapy, biotherapy, etc.
• Cohort 2 only： Presence of other gene mutations, including ALK mutation, MET amplification, HER2 amplification, RAS mutation, etc. after progression on prior third-generation EGFR-TKI treatment.
• Cohort 3 only：Has received the treatment of EGFR-TKI。
• Prior FAK inhibitors treatment.
• Have received systemic administration of potent inhibitors/inducers of CYP3A4, or P-gp inhibitors within 14 days prior to the first dose of treatment/randomization or are expected to receive systemic administration of these drugs during study treatment.
• Has received radiotherapy for study disease or radiotherapeutic area covered for more than 30% of the bone marrow within 28 days prior to the first dose of study treatment/randomization.
• Has had interstitial lung disease (ILD), drug-induced ILD, radiation pneumonia requiring steroid therapy; or diagnosis of clinically active ILD during the screening period.
• Has a prior history of other malignancy within 3 years prior to signing informed consent.
• Has known symptoms of spinal cord compression, active central nervous system (CNS) metastases, and/or carcinomatous meningitis.
• Has a history of severe cardiovascular or cerebrovascular diseases within 6 months prior to the first dose of study treatment/randomization.
• Has known uncontrollable pleural effusion, pericardial effusion, and ascites.

Sponsors & Collaborators

• InxMed (Shanghai) Co., Ltd.: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, China

RECRUITING

MeSH Terms

Interventions

aflutinib

Study Officials

• Caicun Zhou

  Shanghai Pulmonary Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bohong Zhang

CONTACT

+86 18801955197; bohong.zhang@inxmed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2023
• First Posted: August 16, 2023
• Study Start: July 13, 2023
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)