Phase Ib Study of FURMONERTINIB in Patients with NSCLC Having Exon 20 Insertion Mutation

NCT04958967 | Withdrawn Phase 1 DMC

• 1 other identifier: ALSC015AST2818
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 multi-center clinical study. To explore the efficacy and safety of Furmonertinib Mesilate at different doses in locally advanced or metastatic NSCLC patients with EGFR exon 20 insertion mutation. The study plans to enroll 20subjects, including 20 treated patients aThe subjects will receive Furmonertinib Mesilate 240 mg/day or 160mg/day until disease progression, death or intolerability. The primary endpoint is Overall Response Rate (ORR) as Assessed by the Independent Review Committee (IRC); the secondary study endpoints include ORR（ Assessed by the Investigator），DCR，DOR，DpR，PFS，OS，CNS ORR（ Assessed by the Independent Review Committee） In addition, the peripheral blood ctDNA will be collected and analyzed in this study

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• ORR, objective response rate

  IRC assessed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in participants with epidermal growth factor receptor EGFRmutations. These outcome is based on the visual assessment of tumor size in morphological images provided by computed tomography (CT) or magnetic resonance imaging.ORR is defined as the percentage of participants achieving complete response (CR) and partial response (PR) per RECIST version 1.1. CR: Disappearance of all extranodal target lesions; PR: At least a 30% decrease in Sum of the Longest Diameters (SLD) of target lesions, taking as a reference the baseline SLD.

  up to 12 months

Secondary Outcomes (3)

• Duration of Response (DOR)

  up to 2 years

• Disease Control Rate (DCR)

  up to 2 years

• Progression Free Survival (PFS)

  up to 2 years

Study Arms (2)

treated subjects will receive Furmonertinib 240mg/day,

EXPERIMENTAL

treated subjects will receive Furmonertinib 240mg/day, QD, PO, under fasted state, until progressive disease, death or intolerability.

Drug: Furmonertinib 240mg

treated subjects will receive Furmonertinib 160mg/day

EXPERIMENTAL

treated subjects will receive Furmonertinib 160 mg/day, QD, PO, under fasted state, until progressive disease, death or intolerability.

Drug: Furmonertinib 160mg

Interventions

Furmonertinib 240mg DRUG

treated subjects will receive Furmonertinib 240mg/day

treated subjects will receive Furmonertinib 240mg/day,

Furmonertinib 160mg DRUG

treated subjects will receive Furmonertinib 160mg/day

treated subjects will receive Furmonertinib 160mg/day

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or woman aged ≥18 years;
• Histologically or cytopathologically confirmed primary non-small cell lung cancer (NSCLC) with predominant non-squamous cell histology;
• Treated patients: progress or intolerance after receiving at least one and no more than three lines of systemic treatment (including at least one chemotherapy or immunotherapy) for locally advanced or metastatic NSCLC disease; If the completion time of adjuvant or neoadjuvant treatment is less than or equal to 6 months from the time of the first disease progression, it is evaluated in accordance with the criteria for treated patients Treatment-naïve patients t without any systemic anti-tumor therapy for locally advanced or metastatic NSCLC; If the completion time of adjuvant or neoadjuvant treatment is more than 6 months from the time of first disease progression, the patients be eligible for enrollment to the study;
• The Participants should provide enough ctDNA in peripheral blood during the screening period, and at the same time, they should provide enough advanced tumor tissue sections as far as possible for central laboratory testing to confirm the mutation type of EGFR 20 exon (please refer to the manual of central laboratory for details);
• Participants meeting either of the following conditions (in accordance with the AJCC 8th edition TNM stage classification for lung cancer):
• Having at least one measurable lesion (in accordance with RECIST1.1). Note: measurable lesion can neither be subject to local therapy as radiotherapy nor used for biopsy in screening period; if there is only one measurable lesion, this lesion will be permitted to be biopsied. However, the baseline radiological examination can be performed for this lesion at least 14 days after biopsy.
• Adequate organ function as shown in the laboratory test, including: 1)Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; platelet count (PLT) ≥ 100 × 109/L; hemoglobin (HGB) ≥ 90 g/L; 2)Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), AST and ALT ≤ 2.5 × ULN (total bilirubin ≤ 3 × ULN, AST and ALT ≤ 5 × ULN in patients with hepatic metastasis); 3)Creatinine clearance (CrCL) ≥ 50 ml/min (using Cockcroft- Gault formula); Prothrombin time (PT) ≤ 1.5 × ULN;
• ECOG PS score 0-1 at screening, no obvious exacerbation of disease within 2 weeks prior to screening;
• Life expectancy \>12 weeks after the first dose of investigational product;
• Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of investigational product; female subjects of non-childbearing potential may not undergo pregnancy test or contraception. Non-childbearing potential is defined as: 50 years and above, no use of hormone therapy and amenorrhea for at least 12 months; or having received sterilization operation. Female subjects at childbearing age and male subjects agree to take effective contraceptive measures during the study and within 6 months after drug discontinuation;
• Being able to understand and voluntarily participate in the study, and sign the informed consent form.

You may not qualify if:

• Any potential participant who meets any of the following criteria will be excluded fromparticipating in the study:
• NSCLC with predominant squamous cell histology, small cell lung cancer or neuroendocrine carcinoma indicated by Histology or cytology test;
• Expected to receive other anti-tumor therapy other than the investigational product during the study;
• Treated patients: having previously received systematic anti-tumor therapy with 3rd-generation EGFR TKI (marketed drugs or drugs under development) ;
• ）Therapeutic drugs (such as dzd9008, tak788, jnj-372, bocitinib, etc.) for EGFR 20 exon insertion mutation; 2)The third generation of EGFR TKI (marketed or in research drug); 3） The first and second generation EGFR TKI (marketed drugs or drugs in Research) targeting the insertion mutation of EGFR 20 exon had objective remission;
• Having received the following therapies:
• Having been irradiated for \>30% bone marrow or a large area within 4 weeks prior to the first dose of investigational product;
• Having received major surgery within 4 weeks prior to the first dose of investigational product or plan to receive major surgery during the study with exception of the surgical procedures to establish vascular access, biopsy through mediastinoscopy or thoracoscopy;
• Use of a potent CYP3A4 inhibitor within 7 days prior to the first dose of investigational product or a potent CYP3A4 inducer within 21 days prior to the first dose of investigational product;
• use of the traditional Chinese medicine or traditional Chinese medicine preparation with tumor indication, or traditional Chinese medicine or traditional Chinese medicine preparation with adjuvant anti-tumor effect within two weeks prior to the first dose of investigational product or expected to be required during the study;
• Having participated in the clinical trial and received the investigational product or device within 4 weeks or at least 5 half-lives prior to the first dose of investigational product;
• Having received other anti-tumor drugs within 14 days prior to the first dose of investigational product;
• Concurrent spinal cord compression or symptomatic brain metastasis. Subjects with stable brain metastasis will be eligible. Stable brain metastasis is defined as the patients who have completed regular treatment for brain metastasis, are clinically stable or asymptomatic for at least two weeks and do not need steroid therapy. If the investigator considers there is no indication of immediate radical treatment, patients with asymptomatic brain metastasis will be eligible.
• Unstable pleural effusion or peritoneal effusion with obvious symptoms; those with stable clinical symptoms for at least 14 days after drainage of pleural effusion or ascites will be eligible;
• Having a history of other malignant tumor, or other concurrent malignant tumors (except those that have undergone radical operation and have no recurrence within 5 years post operation, e.g., cervical carcinoma in situ, basal cell carcinoma of skin and papillary thyroid carcinoma);

Sponsors & Collaborators

• Allist Pharmaceuticals, Inc.: lead

Study Sites (1)

Shanghai Chest hospital

Shanghai, China

Location

MeSH Terms

Interventions

aflutinib

Study Design

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

Study Record Dates

• First Submitted: July 5, 2021
• First Posted: July 12, 2021
• Study Start: October 1, 2021
• Primary Completion: May 1, 2022
• Study Completion: August 1, 2022
• Last Updated: March 14, 2025

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)