Neoadjuvant Treatment of gBRCA-Mutated HER2-Negative Breast Cancer With HRS-1167 and Famitinib ± Camrelizumab

NCT06516289 | Recruiting Phase 2

• 1 other identifier: SCHBCC-N074
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

BRCA-Mutated Breast Carcinoma; HER2-negative Breast Cancer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• Phase 2: Residual Cancer Burden (RCB)

  Immediately after the surgery

• Phase 2: Event-free survival (EFS)

  Approximately 3 years

• Phase 2: Objective response rate (ORR)

  Immediately after the surgery

• Phase 2: Rate of complete cell cycle arrest (CCCA) in HR+/HER2- breast cancer

  After 4 weeks of therapy

• Phase 2: Adverse events (AEs)

  Up to 6 months

Study Arms (5)

Safety run-in

EXPERIMENTAL

HRS-1167 + famitinib

Drug: HRS-1167; Drug: Famitinib

Phase 2: Cohort A (HR+/HER2-, gBRCAm)

EXPERIMENTAL

HRS-1167 + famitinib, RP2D

Drug: HRS-1167; Drug: Famitinib

Phase 2: Cohort B (HR-/HER2-, gBRCAm)

EXPERIMENTAL

HRS-1167 + famitinib, RP2D

Drug: HRS-1167; Drug: Famitinib

Phase 2: Cohort C (HR+/HER2-, gBRCAm expansion cohort)

EXPERIMENTAL

HRS-1167 + famitinib, (RP2D) + camrelizumab

Drug: HRS-1167; Drug: Famitinib; Drug: Camrelizumab

Phase 2: Cohort D (HR-/HER2-, gBRCAm expansion cohort)

EXPERIMENTAL

HRS-1167 + famitinib, (RP2D) + camrelizumab

Drug: HRS-1167; Drug: Famitinib; Drug: Camrelizumab

Interventions

HRS-1167 DRUG

a highly selective PARP1 inhibitor

Phase 2: Cohort A (HR+/HER2-, gBRCAm); Phase 2: Cohort B (HR-/HER2-, gBRCAm); Phase 2: Cohort C (HR+/HER2-, gBRCAm expansion cohort); Phase 2: Cohort D (HR-/HER2-, gBRCAm expansion cohort); Safety run-in

Famitinib DRUG

a tyrosine kinase inhibitor targeting VEGFR2, PDGFR, and c-kit

Phase 2: Cohort A (HR+/HER2-, gBRCAm); Phase 2: Cohort B (HR-/HER2-, gBRCAm); Phase 2: Cohort C (HR+/HER2-, gBRCAm expansion cohort); Phase 2: Cohort D (HR-/HER2-, gBRCAm expansion cohort); Safety run-in

Camrelizumab DRUG

a humanised anti-programmed death-1 (anti PD-1) antibody

Phase 2: Cohort C (HR+/HER2-, gBRCAm expansion cohort); Phase 2: Cohort D (HR-/HER2-, gBRCAm expansion cohort)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years old, female.
• Patients with histologically confirmed unilateral primary invasive breast cancer who meet the criteria of cT0-4, N1-3, M0 or cT≥3, N0, M0 (inflammatory breast cancer not included).
• Patients with HER-2 negative disease. HER2-negative disease was defined as follows: disease whose HER-2 is 1+ or negative by immunohistochemical (IHC), or fluorescence in situ hybridization (FISH) is negative if IHC is 2+.
• Patients with pathogenic germline BRCA 1/2 mutation.
• According to the RECIST 1.1 criteria, there is at least one measurable objective lesion.
• Eastern Cooperative Oncology Group (ECOG) performance score 0-1.
• Appropriate haematological, hepatic and renal function (no blood transfusion or hematopoietic stimulating factors within 14 days): 1) Absolute number of neutrophils (ANC) ≥ 1.5 x 10\^9/L; 2) Platelets ≥ 100 x 10\^9/L; 3) Hemoglobin ≥ 90 g/L ; 4) White blood cell (WBC) ≥ 3.0×10\^9/L and ≤15×10\^9/L; 5) Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); 6) AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN; 7) serum creatinine (Cr) ≤1.5×ULN, and creatinine clearance (CrCL) ≥50 mL/min (Cockcroft-Gault equation); 8) Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5 ULN with international normalized ratio (INR) ≤1.5 ULN (not receiving anticoagulation); 9) Serum albumin ≥ 2.5g/dL.
• Left ventricular ejection fraction (LVEF) ≥ 50%.
• lead ECG: QT interval corrected by Fridericia method (QTcF) \< 470 msec.
• Urine test: urinary protein \< 2+; If urinary protein ≥ 2+, 24-hour urinary protein quantification must show protein ≤1g.
• Subject is willing and able to comply with the protocol (including contraceptive measures) for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• With good compliance with the planned treatment, are able to understand the follow-up procedures of this study and sigh the informed consent form.

You may not qualify if:

• Patients with any of the following were not enrolled in the study:
• Cancer-related history and treatment history: 1) Bilateral breast cancer; 2) Previous history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS); 3) Previous history of invasive or metastatic breast cancer; 4) Any malignant tumor was diagnosed within 3 years before signing the informed consent, excluding cured cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinoma; 5) Received systemic chemotherapy, systemic targeted therapy and local radiotherapy within 3 years before signing the informed consent; 6) Previously treated with VEGFR small molecule tyrosine kinase inhibitors (such as famitinib, sorafenib, sunitinib, regorafenib, etc.) (except bevacizumab); 7) Prior treatment with PARP inhibitors for any disease;
• Stage IV breast cancer according to the AJCC staging system, 8th edition.
• Inflammatory breast cancer or breast rupture.
• There are clinical symptoms or diseases of the heart that are not well controlled
• Hypertension that is not well controlled by antihypertensive medication: systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg has a history of hypertensive crisis or hypertensive encephalopathy.
• NCI-CTCAE v5.0 grade ≥2 bleeding events occurred within 4 weeks before the first medication, including but not limited to hemoptysis (single episode of hemoptysis volume ≥ 2mL), vaginal bleeding, gastrointestinal bleeding, etc.
• Excessive arterial/venous thrombosis events occurred within 6 months before the first medication, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc. Patients with lower extremity intermuscular venous thrombosis who were evaluated as not requiring anticoagulant therapy, and those whose mural thrombus caused by catheterization had disappeared and did not require drug therapy were considered for enrollment.
• Inability to swallow tablets normally or abnormal gastrointestinal function, which may affect drug absorption as judged by the researcher;
• Receipt of a strong inhibitor of CYP3A4, CYP2D6, P-gp, or BCRP from the date of first dose \<5 times of drug half-lives or 14 days; The interval between receiving treatment with the above enzyme strong inducers and the first dose \< 28 days.
• Evidence of any disease as judged by the investigator (e.g., severe or uncontrolled systemic disease, including severe systemic infection, uncontrolled hypertension, renal transplantation and active bleeding disease, coagulation disorders, platelet dysfunction, severe chronic gastrointestinal disease, or patients with other serious medical conditions);
• Have undergone major surgery other than invasive diagnostic procedures, peripherally inserted central catheter (PICC) procedures, or pathological biopsy within 28 days prior to the first dose, or are expected to undergo major surgery during the study period;
• Unhealed wounds, ulcers, or fractures;
• Active hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] positive and HBV-DNA ≥500IU/ml);
• Hepatitis C infection (defined as a positive test for hepatitis C virus antibody \[HCV-Ab\] and an HCV-RNA test higher than the lower limit of the assay);

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Breast cancer institute of Fudan University Cancer Hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

famitinib; camrelizumab

Study Officials

• Zhi-Ming Shao, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhi-Ming Shao, MD

CONTACT

86-21-641755901105; zhimingshao@yahoo.com

Xi-Yu Liu, MD

CONTACT

86-21-64175590-63202; liu-xiyu@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 1, 2024
• First Posted: July 23, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 12, 2024

Record last verified: 2024-12

Locations

CN (1)