Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial

Li Chen, Yi-Zhou Jiang, Song-Yang Wu, Jiong Wu, Gen-Hong Di, Guang-Yu Liu, Ke-Da Yu, Lei Fan, Jun-Jie Li, Yi-Feng Hou, Zhen Hu, Can-Ming Chen, Xiao-Yan Huang, A-Yong Cao, Xin Hu, Shen Zhao, Xiao-Yan Ma, Ying Xu, Xiang-Jie Sun, Wen-Jun Chai, Xiaomao Guo, Xizi Chen, Yanhui Xu, Xiao-Yu Zhu, Jian-Jun Zou, Wen-Tao Yang, Zhong-Hua Wang, Zhi-Ming Shao, Li Chen, Yi-Zhou Jiang, Song-Yang Wu, Jiong Wu, Gen-Hong Di, Guang-Yu Liu, Ke-Da Yu, Lei Fan, Jun-Jie Li, Yi-Feng Hou, Zhen Hu, Can-Ming Chen, Xiao-Yan Huang, A-Yong Cao, Xin Hu, Shen Zhao, Xiao-Yan Ma, Ying Xu, Xiang-Jie Sun, Wen-Jun Chai, Xiaomao Guo, Xizi Chen, Yanhui Xu, Xiao-Yu Zhu, Jian-Jun Zou, Wen-Tao Yang, Zhong-Hua Wang, Zhi-Ming Shao

Abstract

Purpose: Camrelizumab, an mAb against programmed cell death protein 1 (PD-1), plus nab-paclitaxel exhibited promising antitumor activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC). Famitinib is a tyrosine kinase inhibitor targeting VEGFR2, PDGFR, and c-kit. We aimed to assess the efficacy and safety of a novel combination of famitinib, camrelizumab, and nab-paclitaxel in advanced immunomodulatory TNBC.

Patients and methods: This open-label, single-arm, phase II study enrolled patients with previously untreated, advanced, immunomodulatory TNBC (CD8 IHC staining ≥10%). Eligible patients received 20 mg of oral famitinib on days 1 to 28, 200 mg of i.v. camrelizumab on days 1 and 15, and i.v. nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 in 4-week cycles. The primary endpoint was objective response rate (ORR), as assessed by investigators per RECIST v1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and exploratory biomarkers.

Results: Forty-eight patients were enrolled and treated. Median follow-up was 17.0 months (range, 8.7-24.3). Confirmed ORR was 81.3% [95% confidence interval (CI), 70.2-92.3], with five complete and 34 partial responses. Median PFS was 13.6 months (95% CI, 8.4-18.8), and median DOR was 14.9 months [95% CI, not estimable (NE)-NE]. Median OS was not reached. No treatment-related deaths were reported. Among 30 patients with IHC, 13 (43.3%) were programmed death-ligand 1 (PD-L1)-negative, and PD-L1 was associated with favorable response. PKD1 and KAT6A somatic mutations were associated with therapy response.

Conclusions: The triplet regimen was efficacious and well tolerated in previously untreated, advanced, immunomodulatory TNBC. The randomized controlled FUTURE-SUPER trial is under way to validate our findings. See related commentary by Salgado and Loi, p. 2728.

Trial registration: ClinicalTrials.gov NCT04129996.

©2022 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.
Figure 1.
Study overview. *One patient was diagnosed with a second primary tumor (multiple myeloma) and carried a likely pathogenic germline BRCA1 mutation.
Figure 2.
Figure 2.
Tumor response and survival data. A, Best percentage change from baseline in the target lesion, as assessed by the investigators (n = 46); the best overall response is indicated by color coding of bars and includes assessment of target, nontarget, and new lesions via RECIST v1.1. B, DORs among patients with a confirmed OR (n = 39); the bar length represents the treatment duration for each patient. C and D, Kaplan–Meier curve of PFS and OS. PD, progressive disease; SD, stable disease; mo, months.
Figure 3.
Figure 3.
Genomic and clinicopathologic biomarkers for therapy response. A, The genomic landscape of patients in the FUTURE-C-Plus trial. B and C, Association of variants detected via biopsy and ctDNA using an extraordinary response (relative remission ≥ 80%). D, Detected somatic mutations with an objective response. E–H, Association of age, number of metastatic sites, PD-L1, and PD-L1/CD31 expression with tumor response. *, P < 0.05; †, 0.05 ≤ P < 0.25. Abbreviations: DN, double-negative; SP, single-positive; DP, double-positive; Del, deletion; ins, insertion; PD, progressive disease; SD, stable disease.

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