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

Qingyuan Zhang, Bin Shao, Zhongsheng Tong, Quchang Ouyang, Yuting Wang, Guoying Xu, Shaorong Li, Huiping Li, Qingyuan Zhang, Bin Shao, Zhongsheng Tong, Quchang Ouyang, Yuting Wang, Guoying Xu, Shaorong Li, Huiping Li

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).

Keywords: Apatinib; Camrelizumab; Fuzuloparib; Immunotherapy; PARP; PD-1; TNBC; Triple-negative breast cancer; VEGFR.

Conflict of interest statement

YW, GX, and SL are employees of Jiangsu Hengrui Pharmaceuticals. Other authors have no potential conflict of interest to declare.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Tumor response. A Best percentage change in sum of diameters of the target lesion from baseline in individual patients. B Treatment duration and tumor response. Asterisk (*) symbol represents patients with a partial response
Fig. 2
Fig. 2
Kaplan–Meier curve for progression-free survival in patients with camrelizumab plus apatinib 500 mg and fuzuloparib

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