Neoadjuvant Treatment of gBRCA-Mutated HER2-Negative Breast Cancer With HRS-1167 and Famitinib ± Camrelizumab
NCT Number: NCT06516289
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: BRCA-Mutated Breast Carcinoma|HER2-negative Breast Cancer
Interventions: DRUG: HRS-1167|DRUG: Famitinib|DRUG: Camrelizumab
Sponsor: Fudan University
Sex: FEMALE
Age: ADULT, OLDER_ADULT
Enrollment: 130
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07
Completion Date: 2027-06
Locations: Breast cancer institute of Fudan University Cancer Hospital, Shanghai, Shanghai, 200032, China

Summary:
This study is a prospective, open-label, multi-center, phase II clinical trial designed for HER2-negative breast cancer with pathogenic mutations in the germline gene (gBRCA1/2) that were indicated for neoadjuvant chemotherapy. The characteristics of this study are a precision treatment scheme without chemotherapy, the scheme of HRS-1167 combined with famitinib neoadjuvant therapy for patients with gBRCA mutations is explored, and the efficacy of combined immunotherapy is further explored according to the efficacy of the combination of the two drugs.

Primary Outcome Measures: Safety run-in: Incidence rate of dose-limiting toxicities (DLTs), Incidence rate of DLT will be evaluated in participants in the Safety Run-In, who will be followed for protocol-defined DLT events up to 28±3 days after the first dose of HRS-1167 and famitinib., 28±3 days|Safety run-in: adverse events (AEs), Incidence rate of AEs of any cause will be evaluated in participants in the Safety Run-In according to CTCAE v5.0., 28±3 days|Safety run-in: Serious adverse events (SAEs), Incidence rate of SAEs of any cause will be evaluated in participants in the Safety Run-In according to CTCAE v5.0., 28±3 days|Phase 2: Total Pathologic complete response (tpCR: ypT0/Tis ypN0) rate, Defined as no residual invasive cancer cells are found in the pathological examination of breast and axillary lymph node; if only residual in situ cancer cells are present in the surgical specimens, it can also be considered as achieving a pathological complete response., Immediately after the surgery
Secondary Outcome Measures: Phase 2: Residual Cancer Burden (RCB), RCB will be estimated from routine pathological sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. The pathological variables include bidimensional diameters of the primary tumor bed, the proportion of primary tumor area containing invasive carcinoma, the number of positive lymph nodes, and the diameter of the largest nodal metastasis, Immediately after the surgery|Phase 2: Event-free survival (EFS), Defined as the time from the date of the first study dose to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause., Approximately 3 years|Phase 2: Objective response rate (ORR), Defined as the proportion of patients with complete response (CR) and partial response (PR) by magnetic resonance imaging (MRI) according to RECIST v1.1., Immediately after the surgery|Phase 2: Rate of complete cell cycle arrest (CCCA) in HR+/HER2- breast cancer, Rate of CCCA determined by IHC Ki67 ( Ki67 ≤ 2.7%) between pre- and post-treatment., After 4 weeks of therapy|Phase 2: Adverse events (AEs), Incidence rate of AEs of any cause will be evaluated in participants enrolled in the phase 2 period according to CTCAE v5.0., Up to 6 months|Phase 2: Serious adverse events (SAEs), Incidence rate of SAEs of any cause will be evaluated in participants enrolled in the phase 2 period according to CTCAE v5.0., Up to 6 months|Biomarker analysis1, Gene mutations in the paired tumor and peripheral blood will be tested and analysed to predict therapy response., At baseline, at the end of first 2 cycles (each cycle is 28 days) and immediately after the surgery|Biomarker analysis 2, Gene expression signatures in the paired tumor and peripheral blood will be tested and analysed to predict therapy response., At baseline, at the end of first 2 cycles (each cycle is 28 days) and immediately after the surgery