Fluzoparib in Combination With Camrelizumab and Temozolomide in Advanced Melanoma

Sponsor

Jun Guo (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05983237

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate how well fuzoparib in combination with camrelizumab and temozolomide works in treating patients with advanced, metastatic melanoma with the homologous recombination (HR) pathway gene mutation / alteration.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: Fluzoparib Camrelizumab Temozolomide	Phase 1/Phase 2

Detailed Description

Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a subset of cancer cells with deficiencies in DNA repair pathways. Non-BRCA deficiencies in homologous recombination DNA repair genes could also enhance tumor cell sensitivity to PARP inhibitors. Therefore, PARP inhibitors are also selectively cytotoxic for cancer cells with deficiencies in DNA repair proteins other than BRCA1 and BRCA2.

In melanoma, genetic HR mutation/ alterations are rather common. Retrospective data showed that nearly18-40% of melanoma harbors a mutation in at least 1 of the HR genes in their tumor. The commonly altered genes were ARID1A, FANCA, ATM, BRCA1, ATRX and BRCA2, ATR, BRCA1 BRIP1 and SF3B1. These findings indicate that HR mutations / alterations are frequently observed in metastatic melanoma, and they suggest that PARP inhibitors could potentially be of a great clinical value in a substantial portion of the patients with advanced melanoma.

In this clinical study, clinical efficacy of fluzoparib in combination with camrelizumab and temozolomide will be evaluated by assessing an objective clinical response rate in patients with advanced, metastatic melanoma with the homologous recombination (HR) pathway gene mutation / alteration.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase Ib Study of Fluzoparib in Combination With Camrelizumab and Temozolomide in Advanced Melanoma With Homologous Recombination (HR) Mutation ，a Single-center Open-label Exploratory Clinical Trial

Anticipated Study Start Date :

Aug 31, 2023

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Camre+Fluzo+TMZ This arm will enroll patients who has advanced melanoma with a genetic HR mutation/ alteration .	Drug: Fluzoparib Camrelizumab Temozolomide Fluzoparib 50-150mg bid po, d1-21, q3w Camrelizumab 200mg iv, d1, q3w Temozolomide 50mg/m2-200mg/m2 d1-5,q3w

Arm

Intervention/Treatment

Experimental: Camre+Fluzo+TMZ

This arm will enroll patients who has advanced melanoma with a genetic HR mutation/ alteration .

Drug: Fluzoparib Camrelizumab Temozolomide

Fluzoparib 50-150mg bid po, d1-21, q3w Camrelizumab 200mg iv, d1, q3w Temozolomide 50mg/m2-200mg/m2 d1-5,q3w

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) [6 months]
ORR of Fluzoparib in combination with Camrelizumab and Temozolomide in patients with advanced melanoma with genetic homologous recombination (HR) mutation/ alteration using RECIST v1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of unresectable or metastatic stage III or IV melanoma;
Must have genetic HR and/or SF3B1 mutation/ alteration;
Must have measurable disease based on RECIST 1.1;
Must have an ECOG performance status of 0 to 1;
Must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline;
Anticipated overall survival more than 3 months;
Male and no pregnant female, able to adapt birth control methods during treatment.

Exclusion Criteria:

Previously treated with a PARP inhibitor;
Hypersensitivity to Fluzoparib or Camrelizumab or Temozolomide;
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug;
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug;
Patients with a history of other (including unknown primary) malignancies within 5 years prior to the first dose of trial treatment;