Exelixis (NASDAQ:EXEL) executives and investors spent part of the discussion at a Leerink event focusing on recent renal cell carcinoma (RCC) data, evolving treatment sequencing debates, and the company’s late-stage pipeline plans around its next-generation tyrosine kinase inhibitor (TKI) zanzalintinib. Andrew Peters, senior vice president of strategy and investor relations, also reviewed takeaways from ASCO GU and highlighted expectations for colorectal cancer (CRC) regulatory timing.
ASCO GU: sequencing vs. combining in RCC
Peters said ASCO GU played out “as expected,” with much of the clinician debate centered on whether it is better to combine modalities or sequence them. The conversation touched on LITESPARK-011, which evaluated belzutifan plus lenvatinib in second-line RCC and showed a progression-free survival (PFS) benefit but no statistically significant overall survival (OS) benefit at the time of the second interim analysis, as characterized in the discussion.
On the commercial implications, Peters said the dataset was likely “pretty benign” for Exelixis’ business. If belzutifan/lenvatinib sees some second-line use, he suggested it could drive incremental CABOMETYX plus nivolumab use in the frontline setting, because patients who receive belzutifan/lenvatinib in second line likely would not have received lenvatinib in first line.
Asked about the prospects for OS to eventually become statistically significant, Peters said it was difficult to speculate without details of the statistical plan, but added that it was “hard to see” a very robust survival advantage at this point and emphasized the need to wait for further data.
Tolerability considerations and the “TKI break” concept
Quality-of-life and toxicity considerations were also discussed in the context of combination therapy. Peters highlighted that clinicians weigh the added toxicity of combining agents versus sequencing them. He noted that adverse events such as hypoxia and cardiac dysfunction—raised in the context of belzutifan-based regimens—can be particularly problematic clinically, including questions around baseline patient characteristics and how hypoxia should be monitored.
He added that feedback Exelixis has heard favors sequencing in part because belzutifan monotherapy can provide what he called a “TKI break,” offering patients a different adverse-event profile after prolonged time on IO-TKI combinations or TKI monotherapy.
Merck collaboration: LITESPARK-033 and a shifting RCC market
Peters described LITESPARK-033, a trial that recently started under Exelixis’ collaboration with Merck, as an effort to anticipate how RCC treatment could look in the early 2030s. He linked the study’s rationale to expectations that more patients will have received prior adjuvant pembrolizumab over time, particularly given OS benefit in the adjuvant setting referenced during the event.
According to Peters, LITESPARK-033 is designed to help define the standard of care for patients who progress after adjuvant pembrolizumab—an area he characterized as still an “unanswered question” with new data, where current approaches may default to existing options such as cabozantinib. He said the study aims to test whether zanzalintinib, combined with belzutifan, can help “redefine” treatment in that population.
When asked about Merck’s expected second Phase III trial announcement for zanzalintinib in RCC, Peters declined to provide specifics, saying the partners have agreed not to discuss details until the study is up and running and advising investors to “stay tuned.”
Non-clear cell RCC: STELLAR-304 and the zanzalintinib profile
Peters said Exelixis expects topline data in mid-2026 from a frontline non-clear cell RCC study of zanzalintinib plus nivolumab (STELLAR-304). He underscored that non-clear cell RCC has lacked large randomized trials, and that treatment patterns have been shaped by guideline recommendations informed by a “hodgepodge” of smaller, often single-arm datasets. STELLAR-304, he said, is intended to provide “level one evidence” in a large randomized pivotal study, comparing zanzalintinib plus nivolumab against sunitinib (Sutent).
He sized non-clear cell RCC as about 15% to 20% of RCC on an epidemiology basis and said the goal is to generate differentiating data across response rates, PFS, and ideally OS to establish a new standard of care.
Peters also contrasted zanzalintinib with CABOMETYX on pharmacokinetics and dose management. He said cabozantinib’s approximately four-day half-life can make dose holds and symptom resolution periods lengthy—sometimes 10 days to two weeks or longer—creating challenges for patient management and combinations. Zanzalintinib, he said, was designed to maintain a similar kinase profile while improving the PK profile, with a half-life of “a little under 24 hours,” which he characterized as more user-friendly for combinations and down-titration.
CRC: STELLAR-303 data and December PDUFA timing
In CRC, Peters pointed to the Phase III STELLAR-303 trial of zanzalintinib plus atezolizumab (Tecentriq), which he said read out positively at ESMO and was concurrently published. He said Exelixis is preparing for a potential zanzalintinib launch “later this year” in CRC and referenced a December PDUFA date.
Peters described third-line-plus CRC treatment in the U.S. as roughly split among the SUNLIGHT regimen, TKIs, and chemotherapy. He argued that a key historical gap in CRC has been limited availability of checkpoint inhibitors for many patients, and said STELLAR-303 demonstrated an OS advantage versus standard of care, positioning the combination as a potential new standard of care.
He also discussed an observed dynamic in SUNLIGHT outcomes related to prior bevacizumab exposure, noting that most U.S. patients receive bevacizumab earlier in treatment. Peters said Exelixis has seen no meaningful difference in its data by prior bevacizumab use and also cited no real difference between liver metastases and non-liver metastases subgroups, describing the STELLAR-303 result as robust across stratification factors.
On liver metastases specifically, Peters said the company’s interest in analyzing liver vs. non-liver metastases stems from industry observations that checkpoint inhibitor activity in late-line CRC can differ by liver metastasis status. He said Exelixis was “pleasantly surprised” to see activity across both cohorts and suggested the result supports the idea that the regimen’s activity is not solely driven by VEGF inhibition, pointing instead to additional targets (including TAM kinases and MET/AXL/MER) and effects on tumor microenvironment biology.
Peters clarified that the OS benefit presented at ESMO was in the intent-to-treat population (including patients with and without liver metastases), while the non-liver metastases subgroup OS analysis remained immature due to fewer events. He said the company expects a more mature look at non-liver metastases OS in mid-2026 and expressed hope that it will be positive, which could support messaging around benefit in ITT, liver metastases, and non-liver metastases groups.
Finally, Peters briefly addressed 2026 guidance, saying it reflects continued momentum in the base RCC business and additional momentum from the company’s MET business.
About Exelixis (NASDAQ:EXEL)
Exelixis, Inc is a biotechnology company specializing in the discovery, development and commercialization of small molecule therapies primarily for the treatment of cancer. Building on a platform that leverages model organism genetics and high-throughput screening, the company focuses its research on kinase inhibitors that modulate critical signaling pathways involved in tumor growth and metastasis. Exelixis’s translational research approach aims to advance novel compounds from early-stage discovery through clinical development and regulatory approval.
The company’s most recognized products include CABOMETYX® (cabozantinib), approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma, and COMETRIQ® (cabozantinib) for metastatic medullary thyroid cancer.
