Apatinib and Fluzoparib With or Without Adebrelimab in Previously-treated TP53-mutant Advanced Non-small Cell Lung Cancer

NCT05932264 | Unknown Phase 2

• 1 other identifier: B2023-205-01/MA-NSCLC-II-029
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2, open-label study to evaluate the efficacy and safety of combination of Apatinib and Fluzoparib with or without Adebrelimab in previously-treated TP53-mutant advanced non-small cell lung cancer.

Conditions

NSCLC; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Per RECIST v1.1 criteria, the proportion of patients whose best remission was CR or PR accounted for the total number of evaluable patients.

  up to 1 year

Secondary Outcomes (5)

• Disease Control Rate

  Time Frame: up to 1 year

• DOR

  up to 2 years

• PFS

  up to 2 years

• AEs

  up to 1 years

• Overall survival（OS）

  Up to 2 years

Study Arms (2)

Cohort 1: Apatinib + Fluzoparib

EXPERIMENTAL

Drug: Apatinib + Fluzoparib

Cohort 2: Apatinib + Fluzoparib + Adebrelimab

EXPERIMENTAL

Drug: Apatinib + Fluzoparib + Adebrelimab

Interventions

Apatinib + Fluzoparib DRUG

Cohort 1: Apatinib 375 mg po qd; Fluzoparib 100mg po bid

Cohort 1: Apatinib + Fluzoparib

Apatinib + Fluzoparib + Adebrelimab DRUG

Cohort 2: Apatinib 375 mg po qd; Fluzoparib 100mg po bid; Adebrelimab 1200mg, iv, d1, q3w\]

Cohort 2: Apatinib + Fluzoparib + Adebrelimab

Eligibility Criteria

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

You may qualify if:

• Willing to participate and sign the informed consent in person
• Male or female patients, aged ≥18 years and ≤75 years
• Histologically or cytologically confirmed non-small cell lung cancer with clinical stage IIIB-IV (International Association for the Study of Lung Cancer, 8th Edition)
• TP53 gain-of-function mutations (P151S, Y163C, R175H, L194R, Y220C, R248Q, R248W, R249S, R273C, R273H, R273L, R151S, Y163C, R175H, L194R, R220C, R248W, R249S, R273C, R273H, R273L, R282W) or p53 protein high expression (≥80% nuclear staining positive) confirmed by immunohistochemistry; Consent to provide previously stored tumor tissue specimens or fresh biopsy tumor lesion tissue
• Have at least one measurable lesion (RECIST 1.1 criteria)
• Disease has been progressed after the approved first-line therapy. In brief, patients with positive driver genes (EGFR, ALK, ROS1, BRAF, MET, RET) must have received the corresponding targeted therapy approved in China, and were subsequently treated with platinum-based standard chemotherapy; Patients who are negative for driver genes have to be previously treated with approved chemoimmunotherapy.
• ECOG score 0-1
• Expected survival time ≥12 weeks, as assessed by the investigator.
• Normal organ function, includes:
• Neutrophil count ≥1.5 × 10\^9 / L,
• Platelet count ≥100 × 10\^9 / L,
• Hemoglobin ≥10 g/dL
• Serum creatinine ≤1.5× upper limit of normal (ULN), creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula)
• Total bilirubin ≤ 1.5×ULN
• AST and ALT ≤ 2.5×ULN; Patients with liver metastasis, AST and ALT≤5×ULN, were determined by the investigator

You may not qualify if:

• Non-small cell lung cancer admixed with components of small cell lung cancer or sarcomatoid carcinoma, as confirmed by histology or cytology.
• Patients with \> 2 lines of prior chemotherapy, or previously treated with PARP inhibitor or small-molecule angiogenesis inhibitors.
• Patients with coagulation disorders or who are considered to have a risk of hemorrhage, or the tumor had invades the large blood vessels or wrapped the blood vessels with unclear boundaries on CT or MR imaging.
• Patients with a known allergy to the active or inactive ingredient of any of the drugs in the study, or a history of severe hypersensitivity reaction to any monoclonal antibody
• Symptomatic, uncontrolled brain or leptomeningeal metastases
• Had undergone major surgery within 4 weeks before the start of the study, or had complications/sequelae that have not yet recovered
• Patients with previously or currently diagnosed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
• Suffering from serious or uncontrolled illness, including but not limited to:
• Uncontrollable nausea and vomiting, intestinal obstruction, inability to swallow the study drug, and any gastrointestinal disorders that may interfere with the absorption and metabolism of the drug.
• Patients with respiratory syndrome due to pleural effusion or ascites (≥CTCAE grade 2 dyspnea)
• Active viral infections such as human immunodeficiency virus, hepatitis B, hepatitis C, etc
• Uncontrolled grand mal seizures, unstable spinal cord compression, superior vena cava syndrome, or other mental disorders that prevent the patient from signing informed consent
• Immunodeficiency (other than splenectomy), or other conditions considered by the investigator to be likely to expose the patient to a high risk of toxicity
• A history of active autoimmune disease or possibly recurrent autoimmune disease that may affect vital organ function or require immunosuppressive therapy including systemic corticosteroids
• Systemic treatment with either corticosteroid (\> 10mg/ day prednisone) or other immunosuppressive drugs within 14 days of the study drug; Inhaled or topical steroids and adrenal-replacement doses (≤10mg per day of prednisone) were allowed in the absence of active autoimmune disease. Topical, intraocular, intra-articular, intranasal, and inhaled corticosteroids (with low systemic absorption) were allowed; Physiological alternative doses of systemic corticosteroids (≤10mg/ day prednisone) were allowed; Short-term corticosteroid therapy for prophylaxis (e.g., contrast allergy) or treatment of nonautoimmune conditions (e.g., delayed hypersensitivity due to contact allergens) was permitted

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

apatinib; fluzoparib

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Wenfeng Fang, MD

CONTACT

86-20-87343894; fangwf@sysucc.org.cn

Li Zhang, MD

CONTACT

86-20-87343458; zhangli6@mail.sysu.edu.cn

Study Design

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

Study Record Dates

• First Submitted: June 27, 2023
• First Posted: July 6, 2023
• Study Start: July 1, 2023
• Primary Completion: July 1, 2024
• Study Completion: December 1, 2025
• Last Updated: July 6, 2023

Record last verified: 2023-06

Locations

CN (1)