Adebrelimab Combined with Non-platinum Chemotherapy and Fuzuloparib in Recurrent Platinum-resistant Ovarian Cancer

Official title

Adebrelimab Combined with Non-platinum Chemotherapy and Fuzuloparib in the Treatment of Patients with Recurrent Platinum-resistant Ovarian Cancer (Sunrise Trial): a Single-Arm, Exploratory Study

Overview

The investigators explore the efficacy and safety of adebrelimab (PD-L1 inhibitor) plus Non-platinum chemotherapy and Fuzuloparib (PARP inhibitor) induction therapy followed by maintenance therapy with adebrelimab plus fluzoparib in platinum-resistant relapsed/metastatic ovarian cancer.

Detailed description

Patients with platinum-resistant relapsed/metastatic ovarian cancer are treated with adebrelimab (PD-L1 inhibitor) plus Non-platinum chemotherapy and Fuzuloparib (PARP inhibitor) induction therapy for 6 cycles followed by maintenance therapy with adebrelimab plus fluzoparib

Interventions

• Drug Immunotherapy（Adebrelimab）
  Adebrelimab plus non-platinum chemotherapy（Liposomal doxorubicin/Gemcitabine/ or nab-paclitaxel）and fluzoparib induction therapy followed by maintenance therapy with adebrelimab plus fluzoparib.
• Drug immunotherapy（Adebrelimab）
  anti-PD-L1

Primary outcome measures

• Objective Response Rate(ORR) [Time frame: From the enrollment to the final documentation of response of the last subject (assessed up to 36 months)]

Secondary outcome measures (4)

• Progression-free survival (PFS) [Time frame: From the enrollment to death, lost to follow-up, withdrawal, or study end, whichever occurred first, assessed up to 36 months]
• Disease Control Rate(DCR) [Time frame: From the enrollment to death, lost to follow-up, withdrawal, or study end, whichever occurred first, assessed up to 36 months]
• Overall survival (OS) [Time frame: From the enrollment to the death of last subject or the end of the clinical trial (assessed up to 36 months)]
• Adverse events (AEs) [Time frame: from the initiation of the first dose to 28 days after the last dose，assessed up to 36 months]

Eligibility criteria

Inclusion criteria

• Age 18-70; Female;
• Pathologically (including histologically) confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (hereinafter referred to as ovarian cancer), recurrence within less than six months after the last treatment with platinum-containing chemotherapy;
• Patients have at least one target lesion with measurable dimensions according to RECIST1.1 criteria;
• HRR gene mutation confirmed by testing tissue or blood samples;
• ECOG PS 0-1;
• Major organ functions are normal and meet the following criteria:(1) Blood routine inspection standards must meet: (no blood transfusion within 14 days)a.HB≥100g/L, b. WBC≥3×10\^9/L c. ANC≥1.5×10\^9/L, d.PLT≥100×10\^9/L; (2) Biochemical examination must meet the following standards: a. BIL ≤1.5 times the upper limit of normal (ULN); b. ALT and AST≤2.5×ULN, ALT and AST≤5×ULN in patients with liver metastases; c. Serum Cr≤1.5×ULN
• Activated partial thromboplastin time (APTT) ≤ 1.5 times ULN, prothrombin time (PT) ≤ 1.5 times ULN, international normalized ratio (INR) ≤ 1.5 times ULN, unless the patient is receiving anticoagulation, as long as PT or APTT is within the expected range of anticoagulant use;
• No severe heart, lung, liver or kidney disorders;
• Women of childbearing age must have a pregnancy test (serum) within seven days before enrollment, have a negative result, and be willing to use appropriate methods of contraception during the trial period and eight weeks after the last administration of the test drug;
• Estimated survival≥ 12 weeks;
• Sign a written informed consent form and be able to comply with the visitation and related procedures set out in the program.

Exclusion criteria

1\. Other clinical drug experiments in which other experimental research drugs are used concurrently with the study; 2. Patients with known hypersensitivity to fluzoparib or hypersensitivity to drug-active or inactive ingredients with a similar chemical structure to fluzoparib; 3. Patients with known hypersensitivity to adebrelimab or hypersensitivity to the active or inactive components of the drug having a similar chemical structure to adebrelimab; 4. Inability to swallow oral medications and any gastrointestinal disorders that may interfere with the absorption and metabolism of study medications, such as uncontrolled nausea and vomiting, gastrointestinal obstruction or malabsorption; 5. prior treatment with known or probable immune checkpoint inhibitors; 6. Have any active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); Except vitiligo or recovered childhood asthma/allergies who do not require any intervention in adulthood; 7. Autoimmune-mediated hypothyroidism treated with stable doses of thyroid-replacement hormones; Type I diabetes mellitus with a stable dose of insulin; 8. A history of immunodeficiency, including a positive HIV test, or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation and allogeneic bone marrow transplantation; 9. With unstable systemic diseases, such as hypertension that cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥90 mmHg), severe arrhythmias, etc.; 10. Previous or current idiopathic pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, organising pneumonia, drug-induced pneumonia, or active pneumonia on screening-phase CT; 11. There are cardiac clinical symptoms or diseases that are not well controlled, such as: (1) cardiac insufficiency above NYHA grade 2 (2) unstable angina (3) acute myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention (5) QTc\>470ms; 12. Patients who are pregnant or breastfeeding, or who plan to become pregnant during study treatment; 13. The investigators considered it unsuitable for inclusion.

\-

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fujian Cancer Hospital — Fuzhou

Identifiers

NCT: NCT06600841 · SY-OC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗