Camrelizumab plus famitinib for advanced or metastatic urothelial carcinoma after platinum-based therapy: data from a multicohort phase 2 study

Abstract

BackgroundDual blockade of immune checkpoint and angiogenesis is an effective strategy for multiple cancers. Camrelizumab is a monoclonal antibody against PD-1, and famitinib is a multitargeted receptor tyrosine kinase inhibitor with antiangiogenesis and antiproliferation activities against tumor cells. We conducted an open-label, multicenter phase 2 basket study of camrelizumab and famitinib in eight cohorts of genitourinary or gynecological cancers. Here, findings in cohort of advanced or metastatic urothelial carcinoma with platinum-progressive disease (cohort 2) are presented.MethodsPatients who had progressed after platinum-based chemotherapy for advanced or metastatic disease or had progressed within 12 months after completion of platinum-based (neo)adjuvant therapy were given camrelizumab (200 mg intravenously every 3 weeks) plus famitinib (20 mg orally once daily). Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1.ResultsTotally, 36 patients were recruited. With a median duration from enrollment to data cut-off of 11.9 months (range 6.1–28.5), ORR was 30.6% (95% CI 16.3% to 48.1%). Median duration of response (DoR) was 6.3 months (95% CI 2.1 to not reached). Median progression-free survival (PFS) was 4.1 months (95% CI 2.2 to 8.2), and median overall survival (OS) was 12.9 months (95% CI 8.8 to not reached). Patients with bladder cancer (n=18) had numerically better outcomes, with an ORR of 38.9% (95% CI 17.3% to 64.3%) and a median PFS of 8.3 months (95% CI 4.1 to not reached). Median DoR and OS in this subpopulation had not been reached with lower limit of 95% CI of 4.2 months for DoR and 11.3 months for OS, respectively. Of 36 patients, 22 (61.1%) had grade 3 or 4 treatment-related adverse events, mainly decreased platelet count and hypertension.ConclusionsCamrelizumab plus famitinib showed potent antitumor activity in advanced or metastatic urothelial carcinoma patients after platinum-based chemotherapy. Patients with bladder cancer seemed to have better response to this combination.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.…”

Management of Bladder Cancer Patients with Clinical Evidence of Lymph Node Invasion (cN+)

“…Phase 2 trials also confirm the antitumor effect of Camrelizumab (PD-1 inhibitor) with famitinib in patients with advanced or metastatic BCa who had progressed after platinum-based ChT. The subgroup of BCa patients achieved a median PFS of 8.3 months (95% CI: 4.1 -not reached) and ORR of 38.9% (95% CI: 17.3-64.3%) [237]. Famitinib malate is a tyrosine kinase inhibitor (TKI) against VEGFR-2, PDGFR, c-kit, and FGFR [238].…”

Management of Bladder Cancer Patients with Clinical Evidence of Lymph Node Invasion (cN+)

“…Phase 2 trials also confirm the antitumor effect of camrelizumab (PD-1 inhibitor) with famitinib in patients with advanced or metastatic BCa who had progressed after platinum-based ChT. The subgroup of BCa patients achieved a median PFS of 8.3 months (95% CI: 4.1–not reached), and an ORR of 38.9% (95% CI: 17.3–64.3%) [ 199 ]. Famitinib malate is a tyrosine kinase inhibitor (TKI) against VEGFR-2, PDGFR, c-kit, and FGFR [ 200 ].…”