Phase I study to evaluate the safety and efficacy of rivoceranib (apatinib) and nivolumab in patients with unresectable or metastatic cancer.

18 Background: Due to their immuno-modulatory effects, anti-angiogenic drugs have been clinically investigated in combination with anti-PD-1 therapies. The addition of rivoceranib (apatinib), a highly-selective VEGFR-2 tyrosine kinase inhibitor, is being evaluated in an ongoing 2-part Phase I trial in subjects with locally advanced unresectable/metastatic solid tumors who have received at least 3 doses of nivolumab. A classic 3+3 dose escalation has been completed (Part 1) and the study is currently ongoing with an extension period (Part 2). Herein, we present the safety and preliminary efficacy. Methods: To date, 10 subjects were enrolled in Part 1 while 3 subjects have been enrolled in Part 2. Median number of prior lines of therapy were 3 and 1, respectively, for the two study segments. The major inclusion criteria specified that patients must have received at least 3 doses of nivolumab and are continuing nivolumab therapy. Escalating doses of rivoceranib at 400, 600, and 700 mg po qd was proposed in combination with nivolumab at 240 mg iv q2w to determine the MTD. Best tumor response and time of progression was assessed using RECIST v1.1 and iRECIST. Results: 300 mg rivoceranib was determined as RP2D for Part 2. 5/13 patients had G2/3 hypertension. Common treatment-related AEs were hypertension, hand and foot syndrome, and nausea and immune-related AEs were hypothyroidism and diarrhea. Notably, in 10 evaluable patients, 3 patients had PD and 4 patients showed tumor shrinkage (5-29%). A patient with Malignant Spindled/Epitheloid Sarcoma, who had PD during previous nivolumab treatment has shown tumor reduction, so far, of 9%. A patient with Gastric Cancer, who had stable disease (a 4% increase) after 2 months of nivolumab showed a reduction of 29%, 2 months after introduction of rivoceranib. 2 patients have had stable disease for more than 8 months as of Oct 26, 2018. Conclusions: Preliminary results indicate the potential clinical benefit of a 300 mg starting dose in combination with 240 mg of nivolumab in unresectable/metastatic solid tumors with a tolerable safety profile. Efficacy of ongoing and future patients in Part 2 will be further evaluated. Clinical trial information: NCT03396211.