Agreement supports 12 additional trials including four Phase II studies.
Exelixis reports the expansion of its cabozantinib development program under a CRADA with NCI’s Cancer Therapy Evaluation Program (NCI-CTEP). It has received approval for an initial program of 12 clinical trials. The CRADA, originially inked in November 2011, provides for funding for as many as 20 active clinical trials each year for a five-year period, which Exelixis believes will allow it to broaden the cabozantinib development program in a cost-efficient manner.
Cabozantinib is a tyrosine kinase inhibitor that simultaneously targets the MET and VEGF signaling pathways. In clinical studies, cabozantinib has demonstrated a spectrum of antitumor activity in 12 out of 13 tumor types tested, with regression of metastatic or primary tumor lesions in soft tissue, visceral organs, and the brain; resolution of bone lesions on bone scan; and substantial reductions in pain and narcotic use in patients with castration-resistant prostate cancer (CRPC).
Exelixis initiated a rolling submission of an NDA for cabozantinib in medullary thyroid cancer in December 2011 based on the Phase III EXAM trial. The NDA submission is expected to be completed in the first half of this year. The drug is currently in Phase III development in CRPC.
Three groups of initial trials have been approved under the CRADA to prioritize future development, find new areas of study, and support additional Phase I studies. To prioritize future development, four randomized Phase II trials have the potential to demonstrate cabozantinib’s utility in disease settings where there is substantial unmet medical need. Trials are planned to be conducted in first-line renal cell carcinoma, second-line hepatocellular carcinoma, platinum-resistant or refractory ovarian cancer, and second-line non-small-cell lung cancer. Cabozantinib has previously shown clinical activity in all these settings.
Additional nonrandomized Phase II trials in ocular melanoma and non-small-cell lung cancer are expected to further expand the datasets from earlier studies, which demonstrated the antitumor activity of cabozantinib in these indications. Results from this group of trials could aid in the prioritization of future Phase III trials.
To figure out additional indications worth studying in the future, the CRADA will support single-arm Phase II trials to explore cabozantinib’s potential in endometrial cancer, bladder cancer, and sarcoma. Positive results in these indications could lead to further study in randomized Phase II or Phase III studies. The final group of trials the CRADA will support pertain to Phase I combination trials in additional tumor types as well as a trial to evaluate cabozantinib in pediatric malignancies.
The proposed trials approved under the CRADA will be conducted under an IND held by NCI-CTEP. Protocol development for each of the trials is expected to commence shortly, and the first of these trials is anticipated to begin in around the end of this year or early 2013.