Highlighting Key Developments in Clinical and Strategic Thinking From
Web-Based Sources. Updated July 2017.
New results from CABOSUN, phase 2 trial of cabozantinib vs sunitinib in previously untreated advanced renal cell carcinoma
• IRC confirms cabozantinib significantly improved progression-free
survival compared to sunitinib
• US regulatory submission remains on track for Q3’17
SOUTH SAN FRANCISCO, CA— Exelixis, Inc. has announced that the analysis of the review by a blinded independent radiology review committee (IRC) confirmed the primary efficacy endpoint results of investigator-assessed progression-free survival (PFS) from the CABOSUN randomized phase 2 trial. This trial compares cabozantinib with sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease per the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Per the IRC analysis, cabozantinib demonstrated a clinically meaningful and statistically significant reduction in the rate of disease progression or death as measured by PFS. Exelixis remains on target to complete a supplemental New Drug Application (sNDA) for cabozantinib as a treatment of first-line advanced renal cell carcinoma in the third quarter of 2017.
CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ agreement with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP). Exelixis and the Alliance cooperative group plan to submit these results for presentation at an upcoming international medical meeting.
Calithera Biosciences announces FDA fast track
designation granted to CB-839 for renal cell carcinoma
SOUTH SAN FRANCISCO, CA—Calithera Biosciences, Inc., a clinical stage biotechnology company focused on the development of novel cancer therapeutics, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to CB-839 in combination with everolimus, for the treatment of patients with metastatic renal cell carcinoma (RCC) who have received 2 or more prior lines of therapy. CB-839 is a first-in-class, oral, selective, potent inhibitor of glutaminase being evaluated in Phase 1/2 clinical trials for the treatment of solid tumors including RCC, triple negative breast cancer, non-small cell lung cancer, and melanoma.
The FDA’s Fast Track designation is designed to facilitate the development and expedite the review of drugs and biologics, to treat serious or life threatening conditions, and to fill an unmet medical need. Specifically, Fast Track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support approval, and also provides the opportunity to submit sections of an NDA on a rolling basis as data become available.
AVEO Oncology announces phase 1/2 TiNivo trial of tivozanib
and Opdivo® (nivolumab) in RCC advances to phase 2
CAMBRIDGE, MA—AVEO Oncology announced that its Phase 1/2 AVEO-sponsored TiNivo trial evaluating tivozanib in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, Opdivo® (nivolumab), in subjects with advanced renal cell carcinoma (RCC) has progressed to the Phase 2 portion of the trial.
Advancement of the study into the Phase 2 expansion follows the successful completion of the Phase 1 dose escalation portion of the trial, where tivozanib was administered in two escalating dose cohorts in combination with nivolumab at a constant 240 mg every 2 weeks (n=6). The combination was well tolerated to the full dose and schedule of single agent tivozanib, with no dose limiting toxicities. The full dose tivozanib regimen of 1.5 mg daily for 21 days, followed by a 7 day rest period, is the recommended Phase 2 dose (RP2D) for the expansion portion of the trial, which is expected to enroll up to an additional 20 subjects. The TiNivo study is being led by the Institut Gustave Roussy in Paris under the direction of Bernard Escudier, MD, Chairman of the Genitourinary Oncology Committee. Phase 1 results from the ongoing study will be submitted for presentation at an upcoming scientific meeting.
“The promise of delivering synergistic activity by combining VEGF TKIs and PD-1s in renal cell carcinoma hinges on the tolerability of the combination,” said Dr. Escudier. “Tivozanib has a uniquely favorable tolerability profile as demonstrated in past single agent and combination studies. These initial results are very promising in that we see both evidence of a uniquely tolerable combination as well as early and meaningful activity. I look forward to enrolling the expansion cohort and to establishing a broader understanding for the potential of this compelling combination.”
“Together with the longest progression free survival from a Phase 3 first line RCC study, tivozanib’s tolerability is distinct from other VEGF TKIs, which we believe better position it for use in combination with immunotherapy and other agents,” said Michael Bailey, president and chief executive officer of AVEO. “As our registration strategy for single agent tivozanib reaches key inflection points, with a European regulatory decision expected in the near-term and readout of our US registration-directed TIVO-3 study expected in the first quarter of 2018, our attention is increasing on tivozanib immuno-oncology combinations that have the potential to deliver significantly improved outcomes and tolerability to patients. The TiNivo trial is an important first step in this effort, and we share Dr Escudier’s enthusiasm for the completion of this trial.” KCJ