Ensartinib in Combination With Bevacizumab in ALK-positive NSCLC Patients With TP53 Mutation

NCT05491811 | Active Not Recruiting Phase 2

• 1 other identifier: BD-EN-IV010
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, multicenter, phase II study to investigate the efficacy and safety of Ensartinib plus Bevacizumab in metastatic anaplastic lymphoma kinase (ALK)-rearranged Non-Small Cell Lung Cancer (NSCLC) with TP53 mutation.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 12-month Progression-free Survival (PFS) rate

  Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Progression-free survival (PFS) is defined as the time from beginning of study treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable Response Evaluation Criteria in Solid Tumors (RECIST) assessment.

  The primary analysis of 12-month PFS rate based on investigator assessment will occur when PFS maturity is observed at approximately 12 months after the first patient begin study treatment

Secondary Outcomes (6)

• PFS

  Through study completion, an average of 18 months

• Objective Response Rate (ORR)

  8 weeks

• Duration of Response (DoR)

  12 months

• Disease Control Rate (DCR)

  through study completion, an average of 12 months

• Overall Survival (OS)

  Through study completion, an average of 18 months

Study Arms (1)

Ensartinib and Bevacizumab

EXPERIMENTAL

Ensartinib 225 mg oral once daily with Bevacizumab 7.5mg/kg intravenous every 3 weeks

Drug: Ensartinib; Drug: Bevacizumab

Interventions

Ensartinib DRUG

Participants will receive Ensartinib 225 mg oral once daily from baseline until disease progression, unacceptable toxicity, withdrawal of consent or death.

Ensartinib and Bevacizumab

Bevacizumab DRUG

Participants will receive 7.5 mg/kg intravenous on Day 1 of 21 day cycles (every 3 weeks) from baseline until disease progression, unacceptable toxicity, withdrawal of consent or death.

Also known as: MIL60

Ensartinib and Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed advanced (stage IIIB) or metastatic (stage IV) NSCLC;
• ALK positive with TP53 mutation was confirmed by tissue samples or blood in each center; TP53 mutation detection needs to be confirmed by NGS. ALK positive can be detected by NGS,IHC,RT-PCR and FISH;
• Age ≥ 18 years old;
• ALK-TKI-naive patients, and allowed to have received at most one line previous chemotherapy;
• ECOG Performance status (PS) score is 0-2;
• Karnofsky Performance Status of ≥70;
• Subjects with CNS metastases are only eligible if the CNS metastases are adequately treated with radiotherapy and/or surgery and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 1 week prior to randomization.
• A.Patients receiving radiotherapy or radiosurgery with a dose exceeding 30 Gy will have 3 weeks for neurological stabilization before randomization.
• B.This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Life expectancy of at least 12 weeks;
• Able to swallow oral drugs;
• It has certain organ system functions, defined as follows:
• A. Absolute neutrophil count (ANC) ≥1.5 x 109/L B. Platelets ≥100 x 109/L C. hemoglobin ≥9 g per deciliter (≥90g per liter) note that blood transfusions are permitted to achieve the required hemoglobin level.
• D. Total bilirubin ≤1.5 times upper limit of normal (ULN) E. In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; In case of liver metastasis, ≤5×ULN.
• Female subjects of reproductive age must undergo a negative serum pregnancy test within 3 days before the start of the study medication and be willing to use a medically approved highly effective contraceptive measure (e.g., intrauterine device, contraceptive pill, or condom) during the study and within 3 months after the last administration of the study medication; Male subjects with a female partner of reproductive age should be surgically sterilized or agree to use an effective method of contraception during the study period and for 3 months after the last study dose.

You may not qualify if:

• Only ALK positive or TP53 mutation;
• Patients who have received any previous ALK-TKI treatment;
• Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 \[L858R\] substitution mutations) are excluded. All subjects with non-squamous histology must have been tested locally for EGFR mutation status; use of an FDA-approved test is strongly encouraged (EGFR mutation testing may be performed during the Screening Period, Non-squamous subjects with unknown or indeterminate EGFR status may not be included);
• Subjects with untreated CNS metastases are excluded;
• Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period;
• Active hepatitis B (serum HBV DNA≥1.0E+4 copies /ml\[i.e. 2,000 IU/ml\]), positive for hepatitis C virus antibody, HIV antibody, and treponema pallidum antibody;
• Women of childbearing age who had a positive serum pregnancy test 7 days before the start of treatment, women who were pregnant or lactating, or male and female subjects who did not take effective contraceptive measures or planned to have children during the whole treatment period and 3 months after the end of treatment;
• Patients who have used any of the following drugs within 14 days before the first dose or need to combine them during treatment: drugs at risk for prolonged QTc and/or torsive-tip ventricular tachycardia; CYP3A strong inhibitor or strong inducer;
• Major surgery or immunotherapy was performed within 4 weeks before the first dose; He received radiotherapy within 2 weeks before the first dose.
• Imaging (CT or MRI) showed that the tumor invaded the great blood vessels or it was judged that the tumor was very likely to invade the important blood vessels and cause fatal massive bleeding during the subsequent study
• Previous interstitial lung disease, drug-induced interstitial disease, or any clinically documented active interstitial lung disease; CT scan at baseline revealed the presence of idiopathic pulmonary fibrosis
• Other severe, acute, or chronic medical conditions, including uncontrolled diabetes or medical or psychiatric disorders or laboratory abnormalities, that, in the opinion of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of the study results;
• Other circumstances deemed inappropriate by the investigator for participation in the trial.

Sponsors & Collaborators

• First Affiliated Hospital of Wenzhou Medical University: collaborator
• Shenyang Chest Hospital: collaborator
• Fifth Affiliated Hospital, Sun Yat-Sen University: collaborator
• Sun Yat-sen University: lead
• Second Affiliated Hospital, School of Medicine, Zhejiang University: collaborator
• Hebei Medical University Fourth Hospital: collaborator
• First People's Hospital of Foshan: collaborator
• Guangzhou Institute of Respiratory Disease: collaborator
• Central People's Hospital of Zhanjiang: collaborator
• Guangdong Provincial Agricultural Reclamation Central Hospital: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• West China Hospital: collaborator
• The First Affiliated Hospital with Nanjing Medical University: collaborator
• Yuebei People's Hospital: collaborator
• Yunnan Cancer Hospital: collaborator

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ensartinib; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Zhang Li, MD

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 4, 2022
• First Posted: August 8, 2022
• Study Start: August 1, 2022
• Primary Completion: August 31, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)