Combining Inlyta (axitinib) with inhibitors of the PD-L1/PD-1 pathway seems to be a promising therapeutic approach for patients with advanced renal cell carcinoma (RCC), according to data presented by Pfizer at the European Society for Medical Oncology (ESMO) 2016 Congress, Oct. 7-11 in Copenhagen, Denmark.
The findings come from two Phase 1 clinical trials assessing the safety of combining Inlyta, an oral drug that is approved in the U.S. and E.U. for advanced RCC patients, with Merck and Pfizer’s experimental anti-PD-L1 avelumab or with the anti-PD-1 Keytruda (pembrolizumab).
“Combining immunotherapy agents with currently approved therapies such as Inlyta may provide a meaningful improvement in outcome for patients with renal cancer,” Dr. Chris Boshoff, MD, PhD, head of immuno-oncology, early development and translational oncology at Pfizer Global Product Development, said in a press release.
“The results presented today [at the ESMO congress] indicate that there is a potential additive or synergistic effect between Inlyta and a checkpoint inhibitor in RCC,” Boshoff added.
The Phase 1b, open-label, A4061079 study (NCT02133742) was designed to evaluate the combination of Inlyta plus Keytruda in treatment-naive patients with advanced RCC, with a first dose-finding phase and an expansion phase to test the maximum tolerated dose of Keytruda.
Early data from this trial suggested that the combination had promising anti-tumor activity, with 37 of the 52 enrolled patients (71.2%) achieving objective responses, three of whom had complete responses and 34 who had partial responses. In addition, 10 patients had stable diseases, and only five patients exhibited disease progression.
The Phase 1b, open label, JAVELIN Renal 100 study (NCT02493751) assessed the safety and anti-tumor activity of the combination of Inlyta plus avelumab as a first-line therapy for patients with advanced RCC.
Preliminary data showed that five out of the six patients treated so far (83.3%) had objective response rates, all of which were partial responses. The sixth patient, classified as having stable disease, showed tumor reduction, but not enough to meet the criteria for partial response.
Based on the results of both of these studies, two independent global Phase 3 trials are now enrolling participants. The JAVELIN Renal 101 Phase 3 trial (NCT02684006) will evaluate the combination of Inlyta plus avelumab versus Sutent (sunitinib), which is approved for RCC treatment.
The KEYNOTE-426 Phase 3 trial (NCT02853331) will assess the safety and effectiveness of Inlyta plus Keytruda compared to Sutent alone. Both trials will be assessing these combinations as first-line treatment for patients with advanced RCC.