Antitumor activity and safety of camrelizumab plus famitinib in patients with platinum-resistant recurrent ovarian cancer: results from an open-label, multicenter phase 2 basket study

Abstract

BackgroundCombination treatments with immune-checkpoint inhibitor and antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a notable therapeutic strategy in recurrent ovarian cancer (ROC). We report the results of camrelizumab (an anti-programmed cell death protein-1 antibody) in combination with famitinib (a receptor tyrosine kinase inhibitor) for the treatment of platinum-resistant ROC from an open-label, multicenter, phase 2 basket trial.MethodsEligible patients with platinum-resistant ROC were enrolled to receive camrelizumab (200 mg every 3 weeks by intravenous infusion) and oral famitinib (20 mg once daily). All patients had disease progression during or <6 months after their most recent platinum-based chemotherapy. Primary endpoint was confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 based on investigator’s assessment. Secondary endpoints included disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS), 12-month OS rate and safety profile.ResultsOf the 37 women enrolled, 11 (29.7%) patients had primary platinum resistant, 15 (40.5%) patients had secondary platinum resistant and 11 (29.7%) patients had primary platinum refractory disease. As the cut-off date of April 9, 2021, nine (24.3%) patients had achieved a confirmed objective response, the ORR was 24.3% (95% CI, 11.8 to 41.2) and the DCR was 54.1% (95% CI, 36.9 to 70.5). Patients with this combination regimen showed a median TTR of 2.1 months (range, 1.8–4.1) and a median DoR of 4.1 months (95% CI, 1.9 to 6.3). Median PFS was 4.1 months (95% CI, 2.1 to 5.7), and median OS was 18.9 months (95% CI, 10.8 to not reached), with the median follow-up duration of 22.0 months (range, 12.0–23.7). The estimated 12-month OS rate was 67.2% (95% CI, 49.4 to 79.9). The most common ≥grade 3 treatment-related adverse events were hypertension (32.4%), decreased neutrophil count (29.7%) and decreased platelet count (13.5%). One (2.7%) patient died of grade 5 hemorrhage that was judged possibly related to study treatment by investigator.ConclusionThe camrelizumab with famitinib combination appeared to show antitumor activity in heavily pretreated patients with platinum-resistant ROC with an acceptable safety profile. This combination might provide a novel alternative treatment strategy in platinum-resistant ROC setting and warranted further exploration.Trial registration numberNCT03827837.

A multicenter phase 2 trial of camrelizumab plus famitinib for women with recurrent or metastatic cervical squamous cell carcinoma

“…Reactive capillary endothelial proliferation is a common skin toxicity associated with camrelizumab 28 ; hand-foot syndrome, hypertension, and proteinuria are likely to be associated with famitinib 25 . The incidence of reactive capillary endothelial proliferation in this study was substantially reduced compared with that of camrelizumab monotherapy; this finding was in line with those from other studies that combined camrelizumab with anti-angiogenic agents 27,[29][30][31] . This indicates that the camrelizumabregulated immune response may destroy the dynamic balance between pro-and anti-angiogenic factors.…”

A real-world study of anlotinib as third-line or above therapy in patients with her-2 negative metastatic breast cancer

“…Antiangiogenic therapy and immunotherapy both act on the tumor microenvironment, and previous preclinical studies have shown that immunotherapy combined with anti-angiogenic drugs synergistically inhibit tumor growth and metastasis ( 33 ). Some clinical trials also confirmed the value of antiangiogenic therapy in combination with immunotherapy ( 34 , 35 ). However, the application of anlotinib combined with ICIs in breast cancer has not yet been reported, our present study shows that anlotinib combined with immunotherapy has also achieved good clinical efficacy in metastatic breast cancer.…”

Therapeutic targeting of VEGF and/or TGF-β to enhance anti-PD-(L)1 therapy: The evidence from clinical trials

“…At the cut-off date, 24.3% of patients achieved CR or PR. The median PFS and OS of this group of patients were 4.1 months and 18.9 months, respectively ( 74 ). Sintilimab plus anlotinib was demonstrated efficacy as second-line or later therapy for patients with PD-L1-positive advanced cervical cancer in a phase II trial, with an ORR of 54.8% (23/42) ( 75 ).…”

“…The results from a multicenter phase II basket trial (NCT03827837) showed that the camrelizumab plus famitinib exhibited antitumor activity in patients with platinum-resistant ovarian cancer (OC) ( 74 ). At the cut-off date, 24.3% of patients achieved CR or PR.…”