Combination of famitinib with camrelizumab plus nab-paclitaxel as first-line treatment for patients with immunomodulatory advanced triple-negative breast cancer (FUTURE-C-PLUS): A prospective, single-arm, phase 2 study.

1007 Background: Camrelizumab (anti-PD-1 antibody) and nab-paclitaxel (nab-P) have demonstrated promising anti-tumour activity in patients with immunomodulatory (IM) subtype metastatic triple negative breast cancer (TNBC), with 52.6% of ORR observed in heavily pretreated patients in our previous umbrella trial (FUTURE). As antiangiogenic agents were known to enhance the response to immune checkpoint inhibitors, we assessed the efficacy and safety of novel triplet combination of famitinib (tyrosine kinase inhibitor targeting VEGFR-2, PDGFR and c-kit), camrelizumab and nab-paclitaxel in patients with IM subtype advanced TNBC. Methods: In this prospective, single-arm, phase 2 study, eligible patients were 18-70 years and had treatment-naive IM subtype unresectable locally advanced or metastatic TNBC. IM subtype was defined as CD8+ by immunohistochemistry. Eligible patients received camrelizumab (200 mg iv, d1, 15, q4w) with nab-P (100 mg/m 2 iv, d1, 8, 15, q4w) and famitinib (20 mg po qd, d1-28, q4w). Treatment was continued until disease progression, patient withdrawal, or unacceptable toxic effects. In the absence of intolerable toxicity, nab-P was to be administered for a minimum of 6 cycles. Primary endpoint was objective response rate according to RECIST v1.1. We explored the predictive biomarkers using targeted sequencing with a 484-gene panel. Results: From Oct 2019 to Oct 2020, 48 patients were enrolled. Confirmed objective responses were achieved in 39 (81.3%; 95% CI 70.2%-92.3%) of 48 patients in the intention-to-treat population and in 39 (84.8%; 95% CI 74.4%-95.2%) of 46 patients in the per-protocol population. Median time to response was 1.8 months (95% CI 1.8-2.0 months). With a median follow-up of 9.0 months, progression-free survival (PFS) and duration of response data were not mature. Thirty patients (62.5%) are still on the study treatment. The 9-month PFS rate was 60.2% (95% CI, 43.2% to 77.3%). Grade 3 or 4 adverse events were neutropenia (33.3%), anaemia (10.4%), febrile neutropenia (10.4%), thrombocytopenia (8.3%), hypertension (4.2%), hypothyroidism (4.2%), proteinuria (2.1%), septicemia (2.1%) and immune related myocarditis (2.1%). Adverse events that led to the discontinuation of any agent occurred in 6.3% of the patients. Two patients had treatment-related serious adverse events. No treatment-related deaths were reported. Biomarker analysis showed that somatic mutations of GSK3A may have the potential to predict immunotherapy response. Conclusions: Addition of famitinib to camrelizumab and nab-paclitaxel showed promising antitumour activity as first-line therapy with manageable toxicity profile for IM subtype advanced TNBC patients. Results from ongoing randomized controlled trial FUTURE-SUPER (NCT 04395989) are eagerly awaited. Clinical trial information: NCT04129996 .