Neratinib Tablets Monotherapy for Advanced Solid Tumors With HER2 Mutations

NCT06519110 | Not Yet Recruiting Phase 2

• 1 other identifier: CVL009-C2001
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Evaluating the efficacy of Neratinib tablets monotherapy in treating advanced solid tumors with HER2 mutations.

Conditions

Advanced Solid Tumor

Keywords

HER2 mutation-positive; Non-Small Cell Lung Cancer (NSCLC); Cholangiocarcinoma; Cervical Cancer; Salivary Gland Cancer; Neratinib tablets

Outcome Measures

Primary Outcomes (1)

• Objective response rates of the central nervous system as assessed by the Independent Imaging Evaluation Committee based on RECIST1.1

  Objective response rates of the central nervous system as assessed by the Independent Imaging Evaluation Committee based on RECIST1.1

  Throughout the study for approximately 3.5 years

Secondary Outcomes (3)

• Duration of Response (DoR)

  Throughout the study for approximately 3.5 years

• Progression-Free Survival (PFS)

  Throughout the study for approximately 3.5 years

• Disease Control Rate (DCR)

  Throughout the study for approximately 3.5 years

Study Arms (1)

(Trial group)-Neratinib tablets

EXPERIMENTAL

The subjects enrolled in the study will take Neratinib tablets orally as follows: 120mg in the 1st week, 160mg in the 2nd week, and 240mg from the 3rd week until the end of treatment (starting from C1D15 to the end of treatment). During the Neratinib treatment period, loperamide will be administered on an as-needed basis based on the condition of diarrhea. Neratinib tablets should be taken orally once daily, with the tablet to be swallowed whole with a meal, without crushing, breaking, or chewing. A continuous 28-day medication period constitutes one treatment cycle.

Drug: Neratinib tablets

Interventions

Neratinib tablets DRUG

In the first week, take Neratinib tablets 120mg orally, in the second week take Neratinib tablets 160mg orally, and from the third week until the end of treatment, take Nilotinib tablets 240mg orally (from Cycle 1 Day 15 until the end of treatment).

Also known as: Neratinib

(Trial group)-Neratinib tablets

Eligibility Criteria

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

You may qualify if:

• Age is 18 years or older, and the patient can be male or female;
• Histologically or cytologically confirmed advanced non-small cell lung cancer, cholangiocarcinoma, cervical cancer, and salivary gland cancer patients; those who have failed to respond to ≤2 lines of standard treatment (disease progression after treatment or intolerable toxic side effects of treatment), or have no standard treatment options, or are unable to receive standard treatment;
• Previously underwent second-generation sequencing testing with evidence of HER2 mutation, otherwise, the patient must provide sufficient tissue samples for second-generation sequencing testing in the study's central laboratory, with tissue samples being the primary source; if tissue slices or samples that meet the requirements cannot be obtained, blood samples may be provided for testing.
• According to the RECIST v1.1 criteria (see Appendix 1), there must be at least one measurable lesion; if the only lesion is one that has previously received local treatment (such as radiotherapy, ablation, interventional treatment, etc.), there must be clear radiological evidence of disease progression;
• Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1;
• Predicted survival is 3 months or more;
• Women of reproductive age should agree to use contraceptive measures (such as intrauterine devices, hormonal contraceptives, or condoms) during the study period and for 6 months after the study ends; they must have a negative serum or urine pregnancy test within 7 days prior to study enrollment and must not be breastfeeding; men should agree to use contraceptive measures during the study period and for 6 months after the study ends;
• The subject can understand the nature of this study, and the subject and/or legal representative voluntarily agrees to participate in this trial and signs the informed consent.

You may not qualify if:

• Patients who have previously received treatment with any HER2-targeted tyrosine kinase inhibitors (such as lapatinib, pyrotinib, neratinib, etc.);
• Those who do not meet the following requirements for the washout period from previous anti-tumor treatments before the first administration of the study drug: the washout time from the end of the last dose of previous anti-tumor treatment to the first administration of the study drug (calculated from the end of the last dose) is as follows: chemotherapy ≥3 weeks (oral fluorouracil ≥2 weeks; mitomycin C, nitrosoureas ≥6 weeks), small molecule targeted therapy ≥2 weeks, large molecule drugs (including immunotherapy) ≥4 weeks, radiotherapy ≥4 weeks (local palliative radiotherapy ≥2 weeks), Chinese medicine with anti-tumor indications ≥2 weeks, other anti-tumor treatments ≥4 weeks, investigational drugs or treatments that are not yet marketed ≥4 weeks;
• Received major organ surgery (excluding biopsy) or had significant trauma within 4 weeks before the first administration of the study drug;
• Spinal cord compression or brain metastasis, unless asymptomatic, stable, and has not required steroid treatment for at least 4 weeks before the start of the study treatment (before dosing);
• A history of other malignant tumors within the past 5 years, excluding cured cancers such as cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin;
• Adverse reactions from previous anti-tumor treatments have not recovered to a grade of ≤1 according to CTCAE 5.0 (except for toxicities judged by the investigator to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, thyroid hypothyroidism stable with hormone replacement therapy);
• The presence of uncontrollable third-space fluid accumulation (such as a large amount of pleural effusion, ascites, or pericardial effusion) that cannot be managed by drainage or other methods;
• Patients with gastrointestinal diseases that may affect drug absorption (such as Crohn's disease, intestinal obstruction, active peptic ulcer disease, etc.);
• Patients currently suffering from interstitial lung disease;
• Patients with any cardiac disease, including: (1) unstable angina; (2) clinically significant arrhythmias requiring medication; (3) myocardial infarction; (4) heart failure of grade 3 or higher; (5) echocardiography: left ventricular ejection fraction (LVEF) ≤50%; (6) 12-lead electrocardiogram: QTcF: females \>470 milliseconds, males \>450 milliseconds; (7) any other cardiac disease judged by the investigator to be unsuitable for participating in this trial;
• History of immunodeficiency, including HIV antibody test positive;
• Active hepatitis B or C (HBV DNA, HCV RNA test results at screening are not within the normal range of the central laboratory);
• According to the investigator's judgment, there are other serious accompanying diseases that endanger patient safety or affect the patient's ability to complete the study (such as uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg after taking antihypertensive drugs), diabetes (glycated hemoglobin \>9.0%), autoimmune diseases, etc.);
• The investigator deems the subject unsuitable for other reasons to participate in this study.

Sponsors & Collaborators

• Convalife (Shanghai) Co., Ltd.: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Cholangiocarcinoma; Uterine Cervical Neoplasms; Salivary Gland Neoplasms

Interventions

neratinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Mouth Neoplasms; Head and Neck Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases

Study Officials

• jin Li, ph.D

  Shanghai GoBroad Cancer Hospital China Pharmaceutical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

jin Li, ph.D

CONTACT

021-60571204; lijin@csco.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients with advanced solid tumors (non-small cell lung cancer, cholangiocarcinoma, cervical cancer, salivary gland cancer) with HER2 mutations.

Study Record Dates

• First Submitted: July 16, 2024
• First Posted: July 25, 2024
• Study Start: August 10, 2024
• Primary Completion: February 14, 2026
• Study Completion: April 15, 2026
• Last Updated: July 25, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share