Almonertinib for Advanced NSCLC Patients With Rare Mutations in EGFR

NCT04785742 | Unknown Phase 2

• 1 other identifier: YX-L-202008
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open, phase II clinical trial evaluating the safety and efficacy of high-dose almonertinib in the treatment of rare mutations in locally advanced or metastatic NSCLC patients with EGFR mutations (excluding exon 19 deletion or rare mutations outside L858R). Patients showed EGFR mutations by tissue or blood tests (excluding exon 19 deletion or rare mutations other than L858R), of which 20 exon (20INS) mutations and rare mutations other than 20Ins were classified as two covariates. High-dose amitinib was used for treatment to evaluate the safety and efficacy of the treatment regimen.

Conditions

Safety of Almonertinib

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  To evaluate the security of high-dose Almonertinib for advanced NSCLC patients with rare mutations in EGFR

  36 months

Study Arms (2)

20 exon (20INS) mutation

EXPERIMENTAL

Drug: Almonertinib

Rare mutations except for 20INS

EXPERIMENTAL

Drug: Almonertinib

Interventions

Almonertinib DRUG

Almonertinib

20 exon (20INS) mutation; Rare mutations except for 20INS

Eligibility Criteria

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

You may qualify if:

• \. 18 ≤ age ≤75, regardless of gender. 2. Histologically confirmed locally advanced or metastatic non-scaly NSCLC (including stage IIIB-IV patients who relapsed after previous surgical treatment or were newly diagnosed). According to AJCC edition 8 lung cancer staging criteria).
• \. Previous treatment with second-line chemotherapy (no EGFR-TKI) is allowed. 4. Positive EGFR driver mutation (rare mutation other than 19 exon deletion or L858R) detected by tumor tissue or blood samples.
• \. The Eastern Tumor Tissue Cooperative Group (ECOG) physical status score was 0 or 1 and did not deteriorate in the previous 2 weeks, with a minimum expected survival of 12 weeks.
• \. The patient had at least one tumor lesion that had not received previous local treatment such as irradiation, nor had he received biopsy during the screening period, and it could be accurately measured at baseline, with the longest diameter ≥ 10mm at baseline (short diameter ≥ 15mm for lymph nodes). The measurement method chosen is suitable for accurate repeated measurements and can be computed tomography (CT) or magnetic resonance imaging (MRI). If there is only one measurable lesion and no previous local treatment such as irradiation, it may be accepted as the target lesion, and a baseline evaluation of the tumor lesion shall be conducted at least 14 days after the diagnostic biopsy.
• \. For fertile women, appropriate contraception should be used and breastfeeding should not be performed for 3 months from screening to discontinuation of study treatment. A pregnancy test is negative before administration, or there is no proven risk of pregnancy if one of the following criteria is met:
• A. Postmenopause is defined as amenorrhea over the age of 50 and at least 12 months after cessation of all exogenous hormone replacement therapy.
• B. Women younger than 50 years of age may also be considered postmenopausal if they stop all exogenous hormone therapy for 12 months or more and their luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within the laboratory post-menopausal reference range.
• C. Has undergone irreversible sterilization, including hysterectomy, bilateral oophorectomy or bilateral salpingectomy, except for bilateral tubal ligation.
• \. Male patients should use barrier contraception (i.e., condoms) from screening until 3 months after treatment is discontinued.
• \. The subject is willing to participate and sign the informed consent in person.

You may not qualify if:

• \. Have received any of the following treatments:
• A. Patients who underwent major surgery within 4 weeks prior to the first dosing of the study drug;
• B. Patients who received more than 30% bone marrow irradiation or received large area radiotherapy within 4 weeks prior to the first dosing of the study drug;
• C. Study drugs that had used a CYP3A4 inhibitor, inducer, or a narrow therapeutic window with a CYP3A4-sensitive substrate within 7 days before first administration.
• \. Patients with other malignancies requiring standard treatment or major surgery within 2 years of the first dosing of study therapy.
• \. At the start of the study, there were unmitigated residual toxicity from previous treatment greater than CTCAE grade 1, except for grade 2 neurotoxicity caused by hair loss and previous chemotherapy.
• \. Spinal cord compression or brain metastasis, unless asymptomatic, stable, and does not require steroid therapy for at least 2 weeks prior to first dosing of study therapy.
• \. Any serious or poorly controlled systemic disease, as determined by the investigator, such as poorly controlled hypertension, active bleeding susceptibility, or active infection. There is no need to screen for chronic diseases.
• \. Full absorption of amitinib may be affected by refractory nausea, vomiting, or chronic gastrointestinal disorders, inability to swallow study drugs, or previous extensive enterectomy.
• \. Satisfy one of the following cardiac test results:
• A. Average corrected QT interval (QTC) \> 470 msec from three resting electrocardiogram (ECG) examinations, QT interval correction (QTCF) was performed using Fridericia's formula;
• B. Resting ECG suggests the presence of a variety of clinically significant rhythm, conduction, or ECG morphological abnormalities (such as complete left bundle branch block, degree 3 atrioventricular block, degree 2 atrioventricular block, and PR interphase \> 250 Msec);
• C. The presence of any factors that increase the risk of prolonged QTC or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of long QT syndrome or sudden unexplained death of an immediate family member under 40 years of age, or any combination drug that prolongs QT interval;
• D. Left ventricular ejection fraction (LVEF) ≤40%.
• \. Any history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid treatment, or evidence of clinically active interstitial lung disease.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Location

MeSH Terms

Interventions

aumolertinib

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: March 8, 2021
• Study Start: December 31, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 8, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)