fluzoparib and camrelizumab in treating patients with r/m npc that progressed after first-line chemotherapy

Conditions: Nasopharyngeal Carcinoma; Nasopharyngeal Cancer

Summary: the aim of this study is to define the efficacy and safety of fluzoparib and camrelizumab in treating patients with recurrent/metastatic nasopharyngeal carcinoma that progressed after first-line chemotherapy.

currently, the standard first-line treatment for recurrent/metastatic nasopharyngeal carcinoma is cisplatin-based chemotherapy. the recommended subsequent line therapy is single-agent chemotherapy or single-agent pd-1 antibody (nivolumab or pembrolizumab), according to nccn guidelines (head and neck cancer, version 2021.3). however, the efficacy of nivolumab or pembrolizumab in subsequent line setting is limited, range from 20-30%. in order to improve the efficacy, we launch this study to evaluate whether combination treatment of parp inhibitor (fluzoparib) and pd-1 antibody (camrelizumab) has the potential to increase efficacy in the subsequent line treatment, meanwhile has tolerable adverse effect.

Eligibility criteria:
inclusion criteria: 1. sign an informed consent; 2. age older than 18 years old and younger than 75 years old; 3. patients with histologically confirmed recurrent/metastatic nasopharyngeal carcinoma, that progressed after at least first-line chemotherapy, according to recist 1.1 criteria; 4. no previous treatment of pd-1/l1 inhibitors, ctla-4 inhibitors, other checkpoint inhibitors or immune modulation therapy, or parp inhibitors; 5. at least one lesion that fulfills the criteria of "evaluable disease" per recist 1.1 criteria; 6. anticipated overall survival more than 3 months; 7. satisfactory performance status: ecog (eastern cooperative oncology group) scale 0-2; 8. normal organ function; 9. hbv dna\<500 iu/ml（or 2500 copies/ml）and hcv rna negative ; 10. male and no pregnant female, able to adapt birth control methods during treatment. exclusion criteria: 1. hypersensitivity to fluzoparib or camrelizumab; 2. symptomatic spinal cord compression, or high-risk to develop pathological fracture that requires urgent surgery or radiation; 3. necrotic disease, high-risk of massive bleeding; 4. suffered from malignant tumors, except cervical carcinoma in situ, papillary thyroid carcinoma, or skin cancer (non- melanoma) within five years; 5. severe, uncontrolled heart disease, such as more than nyha ii heart failure, unstable angina pectoris, myocardial infarction within 1 year prior to signing inform consent, severe arrhythmia that requires urgent intervention; 6. previous treatment of pd-1/l1 inhibitors, ctla-4 inhibitors, other checkpoint inhibitors or immune modulation therapy, or parp inhibitors; 7. receive vaccine or live vaccine within 28 days prior to signing the informed consent; 8. still suffered from adverse effect (more than ctcae grade 1), that results from previous treatment; 9. severe, uncontrolled infections within 28 days prior to signing inform consent; 10. active, known or suspected autoimmune disease; type i diabetes, hypothyroidism those only need hormone replacement therapy, vitiligo or inactive asthma who don't need systemic therapy can recruit; 11. hiv positive; 12. diagnosed as active pulmonary tuberculosis within one year before signing inform consent; or diagnosed as active pulmonary tuberculosis more than one year, but did not receive standardized anti-tuberculosis treatment; 13. hepatitis b surface antigen (hbsag) positive and hbv-dna ≥500iu/ml, or 2500cps/ml; positive hcv rna; 14. history of drug abuse, drug taking, alcohol abuse; 15. other diseases which may influence the safety or compliance of the clinical trial, such as mental illness, or their family and society factors; 16. women of child-bearing potential who are pregnant or breastfeeding.

Keywords: parp inhibitor fluzoparib checkpoint inhibitor pd-1 inhibitor camrelizumab