A phase Ib study of camrelizumab in combination with apatinib and fuzuloparib in patients with recurrent or metastatic triple-negative breast cancer

Abstract

Background Strategies to improve activity of immune checkpoint inhibitors for triple-negative breast cancer (TNBC) are needed. Preclinical studies showed that antiangiogenic agents and poly (ADP-ribose) polymerase (PARP) inhibitors might sensitize tumors to immunotherapy. Here, we investigated the tolerability, safety, and preliminary antitumor activity of camrelizumab, an anti-PD-1 antibody, in combination with apatinib, a vascular endothelial growth factor receptor-2 inhibitor, and fuzuloparib, a PARP inhibitor, in patients with recurrent or metastatic TNBC. Methods This phase Ib study included a dose-finding part and a dose-expansion part. In the dose-finding part, a 3 + 3 dose escalation scheme was introduced. Patients were given camrelizumab (200 mg every 2 weeks) plus apatinib (375 mg or 500 mg once daily) and fuzuloparib (starting dose 100 mg twice daily) every 28-day cycle. After evaluation of the tolerability and safety of the dosing regimens, a clinical recommended dose was determined for the dose-expansion part. The primary endpoint was dose-limiting toxicity (DLT). Results A total of 32 patients were enrolled. Three patients received camrelizumab 200 mg + apatinib 375 mg + fuzuloparib 100 mg, and 29 received camrelizumab 200 mg + apatinib 500 mg + fuzuloparib 100 mg (clinical recommended dose). No DLTs were observed in either group. The most common grade ≥ 3 treatment-related adverse events were decreased white blood cell count (20.7%), hypertension (13.8%), decreased neutrophil count (10.3%), and increased aspartate aminotransferase (10.3%). Two patients discontinued study treatment due to immune-mediated hepatitis (n = 1) and anemia, decreased platelet count, decreased white blood cell count, increased alanine aminotransferase, increased aspartate aminotransferase, and increased γ-glutamyltransferase (n = 1). One patient died of unknown cause. Two (6.9% [95% CI, 0.9–22.8]) of 29 patients with camrelizumab 200 mg + apatinib 500 mg + fuzuloparib 100 mg had objective response. The disease control rate was 62.1% (95% CI, 42.3–79.3). The median progression-free survival was 5.2 months (95% CI, 3.6–7.3), and the 12-month overall survival rate was 64.2% (95% CI, 19.0–88.8). Conclusions Combination of camrelizumab plus apatinib and fuzuloparib showed manageable safety profile and preliminary antitumor activity in patients with recurrent or metastatic TNBC. Trial registration ClinicalTrials.gov NCT03945604 (May 10, 2019).

Small molecule agents for triple negative breast cancer: Current status and future prospects

“…In the ITT population, DCR was 87 %, CBR was 50 %, mPFS was 8.1 months, and mOS was not achieved, with a 1-year OS rate of 68.3 %. The combination of camrelizumab and apatinib with fluzopanib also showed good safety and significant anti-tumor activity [46] . In a phase 1b clinical trial, the combination strategy was used in 32 patients with relapsed or metastatic TNBC.…”

Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients

“… 86 Research on the therapeutic effectiveness of PD-1 and PD-L1 inhibitors has mainly been conducted in patients with triple-negative breast cancer. 87 Nevertheless, attempts are currently being made to explore the efficacy of PD-1 and PD-L1 inhibitors in patients with HR+/HER2+ ABC. The combination of T-DM1 and atezolizumab has the potential to enhance the toxicity of anti-HER2 drugs and simultaneously strengthen anti-tumor immunity.…”

Targeted Therapy Breakthrough: Apatinib Enhances Neoadjuvant Chemotherapy in Triple- Negative Breast Cancer

“…for neoadjuvant and salvage therapy in TNBC [1,[16][17][18][19] , achieving satisfactory pathological complete response rates and prognoses. Studies have also indicated that PD-1 inhibitors can signi cantly enhance the antitumor e cacy of anthracycline drugs and reduce the risk of TNBC recurrence.…”