A Phase II Study of Efficacy and Safety of Combination of Apatinib and Fluzoparib With or Without Adebrelimab in Previously-treated TP53-mutant Advanced Non-small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Apatinib + Fluzoparib
- Conditions
- NSCLC
- Sponsor
- Sun Yat-sen University
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Objective Response Rate
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
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.
Detailed Description
This study is an open-label, prospective phase II study to evaluate the efficacy and safety of of combination of Apatinib and Fluzoparib with or without Adebrelimab in previously-treated TP53-mutant advanced non-small cell lung cancer. The study is divided into 2 cohorts. Cohort 1 is a two-drug cohort \[Apatinib 375 mg po qd; Fluzoparib 100mg po bid\], and cohort 2 is a three-drug cohort \[apatinib 375 mg po qd; fluzoparib 100mg po bid; Adebrelimab 1200mg, iv, d1, q3w\]. The sample sizes of these two cohorts were determined according to Simon's Two-Stage Design, and enrollment of cohort 2 will be initiated after the enrollment of cohort 1 is completed. Ultimately, 34 patients are enrolled in the cohort 1 and 26 in the cohort 2.
Investigators
Li Zhang, MD
Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •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,
Exclusion Criteria
- •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)
Arms & Interventions
Cohort 1: Apatinib + Fluzoparib
Intervention: Apatinib + Fluzoparib
Cohort 2: Apatinib + Fluzoparib + Adebrelimab
Intervention: Apatinib + Fluzoparib + Adebrelimab
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: up to 1 year
Per RECIST v1.1 criteria, the proportion of patients whose best remission was CR or PR accounted for the total number of evaluable patients.
Secondary Outcomes
- AEs(up to 1 years)
- Overall survival（OS）(Up to 2 years)
- Disease Control Rate(Time Frame: up to 1 year)
- DOR(up to 2 years)
- PFS(up to 2 years)