Trial Title:
Apatinib and Fluzoparib With or Without Adebrelimab in Previously-treated TP53-mutant Advanced Non-small Cell Lung Cancer
NCT ID:
NCT05932264
Condition:
NSCLC
Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Apatinib
Fluzoparib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Apatinib + Fluzoparib
Description:
Cohort 1: Apatinib 375 mg po qd; Fluzoparib 100mg po bid
Arm group label:
Cohort 1: Apatinib + Fluzoparib
Intervention type:
Drug
Intervention name:
Apatinib + Fluzoparib + Adebrelimab
Description:
Cohort 2: Apatinib 375 mg po qd; Fluzoparib 100mg po bid; Adebrelimab 1200mg, iv, d1,
q3w]
Arm group label:
Cohort 2: Apatinib + Fluzoparib + Adebrelimab
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Willing to participate and sign the informed consent in person
2. Male or female patients, aged ≥18 years and ≤75 years
3. Histologically or cytologically confirmed non-small cell lung cancer with clinical
stage IIIB-IV (International Association for the Study of Lung Cancer, 8th Edition)
4. 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
5. Have at least one measurable lesion (RECIST 1.1 criteria)
6. 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.
7. ECOG score 0-1
8. Expected survival time ≥12 weeks, as assessed by the investigator.
9. Normal organ function, includes:
1. Neutrophil count ≥1.5 × 10^9 / L,
2. Platelet count ≥100 × 10^9 / L,
3. Hemoglobin ≥10 g/dL
4. Serum creatinine ≤1.5× upper limit of normal (ULN), creatinine clearance ≥
60ml/min (Cockcroft-Gault formula)
5. Total bilirubin ≤ 1.5×ULN
6. AST and ALT ≤ 2.5×ULN; Patients with liver metastasis, AST and ALT≤5×ULN, were
determined by the investigator
7. Normal coagulation function: INR and PT≤ 1.5 ×ULN
10. The pregnancy test is negative at enrollment. To be enrolled, men or women are
required to commit to using adequate, effective contraception or abstinence from sex
from the start of the study until the end of the study and for 3 months after the
last dose of the study drug
11. The toxic effects of any previous treatment have returned to ≤CTCAE1 or baseline
level
12. Stopping other antineoplastic therapy including but not limited to chemotherapy,
radiotherapy and surgery 4 weeks before receiving the study drugs; targeted therapy
should be discontinued for at least 5 half-lives of the corresponding drug before
receiving the study drugs.
Exclusion Criteria:
1. Non-small cell lung cancer admixed with components of small cell lung cancer or
sarcomatoid carcinoma, as confirmed by histology or cytology.
2. Patients with > 2 lines of prior chemotherapy, or previously treated with PARP
inhibitor or small-molecule angiogenesis inhibitors.
3. 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.
4. 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
5. Symptomatic, uncontrolled brain or leptomeningeal metastases
6. Had undergone major surgery within 4 weeks before the start of the study, or had
complications/sequelae that have not yet recovered
7. Patients with previously or currently diagnosed myelodysplastic syndrome (MDS) or
acute myeloid leukemia (AML)
8. 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.
9. Patients with respiratory syndrome due to pleural effusion or ascites (≥CTCAE grade
2 dyspnea)
10. Active viral infections such as human immunodeficiency virus, hepatitis B, hepatitis
C, etc
11. Uncontrolled grand mal seizures, unstable spinal cord compression, superior vena
cava syndrome, or other mental disorders that prevent the patient from signing
informed consent
12. Immunodeficiency (other than splenectomy), or other conditions considered by the
investigator to be likely to expose the patient to a high risk of toxicity
13. A history of active autoimmune disease or possibly recurrent autoimmune disease that
may affect vital organ function or require immunosuppressive therapy including
systemic corticosteroids
14. 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
15. Bleeding tendency and history of thrombosis:
1. Any bleeding event of CTCAE2 grade within 3 months before screening or of CTCAE
grade 3 or higher within 6 months before screening
2. They have active bleeding or abnormal coagulation function, have a tendency to
bleed, or are receiving thrombolytic or anticoagulant therapy
3. Patients require anticoagulant therapy with drugs such as warfarin or heparin
4. Long-term antiplatelet therapy (e.g., aspirin, clopidogrel) is required.
5. Thrombotic or embolic events such as cerebrovascular accident (including
transient ischemic attack), pulmonary embolism within the past 6 months
16. History of severe cardiovascular disease:
1. New York Heart Association (NYHA) grade 3 and 4 congestive heart failure
2. Unstable angina or newly diagnosed angina or myocardial infarction within 12
months before screening
3. Arrhythmias requiring therapeutic intervention (patients taking beta-blockers
or digoxin are eligible)
4. CTCAE≥ grade 2 valvular heart disease
5. Hypertension that cannot be controlled with medications (systolic blood
pressure > 150 mmHg or diastolic blood pressure > 100 mmHg)
17. Patients who were pregnant or breastfeeding, or expected to plan to become pregnant
during the study treatment
18. Any previous or current medical conditions, treatments, or laboratory abnormalities
that may interfere with the results of the study or prevent the patient from
participating fully in the study, or the investigator considers the patient to be
unsuitable for the study; Patients could not receive platelet or red-cell
transfusions for 4 weeks before starting the study drug
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-Sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Contact:
Last name:
Wenfeng Fang, MD
Phone:
86-20-8734-3894
Email:
fangwf@sysucc.org.cn
Contact backup:
Last name:
Li Zhang, MD
Phone:
86-20-87343458
Email:
zhangli6@mail.sysu.edu.cn
Start date:
July 2023
Completion date:
December 2025
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05932264
