Combining Camrelizumab and Fluzoparib for TP-53 Mutated Endometrial Cancer

Efficacy and Safety of Camrelizumab Plus Albumin-bound Paclitaxel/Carboplatin Followed by Camrelizumab With or Without Fluzoparib Maintenance Therapy for TP-53 Mutated Recurrent or Metastatic Endometrial Cancer: A Phase II Trial

This study is testing if combining two treatments, camrelizumab and fluzoparib, can help people with TP-53 mutated endometrial cancer that has come back or spread.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 117 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (Academic / other)
• Drugs / interventions: chemotherapy, radiation, prednisone, camrelizumab, Dostarlimab, Durvalumab, immunotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06413992 on ClinicalTrials.gov

What this trial studies

This Phase II trial evaluates the safety and efficacy of camrelizumab combined with fluzoparib maintenance therapy in patients with recurrent or metastatic endometrial cancer that has TP-53 mutations. The study aims to optimize treatment strategies by exploring the therapeutic significance of homologous recombination deficiency in this patient population. It builds on previous research indicating that chemotherapy combined with immunotherapy may improve outcomes for these patients, despite mixed results in prior studies. The trial will also assess the prevalence of specific genetic markers in a Chinese cohort.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with recurrent or metastatic endometrial cancer and confirmed TP-53 mutations.

Not a fit: Patients who have previously received immune checkpoint blockade or PARP inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and quality of life for patients with TP-53 mutated endometrial cancer.

How similar studies have performed: Previous studies have shown mixed results with similar approaches, indicating a need for further investigation in this specific patient population.

Eligibility criteria

Inclusion Criteria:

* Age ≥18
* Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG): 0-2. Expected survival ≥ 6 months.
* Patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) 2009 stage III-IV endometrial cancer or recurrent endometrial cancer after ≤ 1 line of platinum-based chemotherapy (including neoadjuvant, adjuvant, and concurrent chemotherapy). For patients who have failed platinum-based chemotherapy, a platinum-free interval of ≥ 12 months is required.
* No restriction on pathological type, abnormal p53 expression indicated by immunohistochemistry, and confirmation of TP53 gene mutation by Sanger sequencing or next-generation sequencing (NGS).
* No prior treatment with immune checkpoint blockade (ICB) or poly (ADP-ribose) polymerase inhibitor (PARPi).
* Discontinuation of previous radiation therapy, chemotherapy, or hormone therapy for at least 4 weeks.
* Adequate organ function as follows (no use of drugs containing blood components or corrective treatment with hematopoietic growth factors in the 7 days prior to randomization): Aspartate Aminotransferase (AST) and Alanine Transaminase (ALT) ≤ 2.5 times the upper limit of normal (≤ 5 times for patients with liver metastasis) and total bilirubin ≤ 1.5 times the upper limit of normal; serum creatinine ≤ 1.5 times the upper limit of normal; platelets ≥ 90,000 cells/mm3, hemoglobin ≥ 90 g/L, and neutrophils ≥ 1,500/mm3.
* Thyroid function prior to randomization: Thyroid-stimulating hormone (TSH) level ≤ 1 times the upper limit of normal, or if TSH is not within the normal range, free T4 ≤ 1 times the upper limit of normal.
* Peripheral neuropathy grade \< 2 (Common Terminology Criteria for Adverse Events, CTCAE 5.0) before treatment.
* Signed informed consent and ability to provide tumor tissue samples from initial diagnosis/recurrence for homologous recombination deficiency (HRD) testing.
* Willingness to comply with clinic visits and follow-up.

Exclusion Criteria:

* Currently participating in another clinical trial or within 4 weeks since completing another clinical trial.
* Known allergy to any components of the investigational drug.
* Previous treatment with immune checkpoint inhibitors, including but not limited to other anti-PD-1 and anti-PD-L1 antibodies.
* Patients requiring the use of immunosuppressive medications.
* Previous treatment with poly (ADP-ribose) polymerase inhibitors (PARPi).
* Patients requiring systemic or absorbable topical corticosteroids at an immunosuppressive dose, or patients who have used prednisone or equivalent drugs at a dose \>10 mg/day in the two weeks prior to taking the study drug.
* Patients with any active autoimmune disease or a history of autoimmune diseases, including but not limited to active hepatitis, pneumonia, uveitis, colitis (inflammatory bowel disease), pituitary inflammation, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, excluding resolved childhood asthma/atopic diseases and vitiligo. Patients with intermittent use of bronchodilators or other medical interventions for asthma should also be excluded.
* Patients in the active infectious phase requiring antimicrobial treatment (e.g., antibiotics, antiviral drugs, antifungal drugs).
* History of immunodeficiency, including human immunodeficiency virus (HIV) seropositivity or other acquired or congenital immunodeficiency diseases.
* Uncontrolled clinically significant cardiac symptoms or diseases within the past year, including but not limited to New York Heart Association (NYHA) class II or higher heart failure, unstable angina, myocardial infarction within the past year, atrial fibrillation, clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, PR interval \>250 ms, or QTc ≥470 ms.
* Arterial or venous thrombosis within the past 6 months.
* Poorly controlled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) despite antihypertensive medication, proteinuria ≥(++) and 24-hour total urinary protein \>1.0 g.
* Coagulation abnormalities (international normalized ratio \[INR\] \>2.0, prothrombin time \[PT\] \>16s), bleeding tendency, or receiving thrombolytic or anticoagulant therapy.
* Patients with other malignant tumors within the past 5 years, excluding basal cell carcinoma of the skin and squamous cell carcinoma of the skin.
* Vaccination with live vaccines within 4 weeks prior to the first administration of the investigational drug. Note: Administration of inactivated seasonal influenza vaccines is allowed.
* History of substance abuse with psychotropic drugs and unable to quit, or patients with psychiatric disorders.
* The investigator believes that any other medical, psychiatric, or social factors may affect the rights, safety, ability to sign informed consent, patient's completion of the study, or interpretation of study results.

Where this trial is running

Beijing, Beijing Municipality

• Cancer Hospital, Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Guangwen Yuan, Md — Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Study coordinator: Shuangzheng Jia, Ph D

Conditions Endometrial Carcinoma; TP53 Mutation; Recurrent or Metastatic; TP53-mutated, Endometrial Carcinoma,Camrelizumab, Fluzoparib