Exelixis (NASDAQ:EXEL) is positioning zanzalintinib, or “Zanza,” as the centerpiece of a broad oncology development strategy, Andrew Peters, the company’s senior vice president of strategy and investor relations, said during a discussion with Stifel Senior Biotech Analyst Stephen Willey.
Peters said the company is focused on building “franchises” around zanzalintinib, including in colorectal cancer and renal cell carcinoma, with seven ongoing or planned pivotal studies. He highlighted STELLAR-303, the colorectal cancer study supporting an upcoming December PDUFA date in third-line colorectal cancer, as a foundation for the company’s efforts in that tumor type.
“Our job…is just focusing and being competitive and trying to gain as much market share across all of those segments as possible,” Peters said. He added that Exelixis does not view zanzalintinib plus atezolizumab as targeting only a narrow patient subset, citing consistent benefit across subgroups in the study’s forest plot.
Additional Colorectal Cancer Data Expected
Willey asked about a pre-specified overall survival analysis in patients without liver metastases, with data expected around midyear. Peters said additional positive data would strengthen the company’s discussions with physicians and patients and could complement the overall intent-to-treat results.
He described the update as part of the standard regulatory review process, particularly for survival data. Peters said patients with liver metastases tend to experience events faster, which contributed to the timing difference between the broader data presentation and the non-liver-metastasis analysis.
Exelixis is also studying zanzalintinib in STELLAR-316, an early-stage colorectal cancer trial involving patients who are minimal residual disease positive after definitive therapy. Peters said the current standard for these patients is “watch and wait,” despite ctDNA-positive patients being at high risk of recurrence.
STELLAR-316 is evaluating zanzalintinib alone and in combination with pembrolizumab. Peters said Exelixis is working with Natera and Merck to help identify patients and support enrollment. He said company executives have expressed optimism that enrollment could be brisk because of the unmet need in this setting.
Dosing Strategy and Safety Considerations
Addressing questions about the 100 mg dose and median dose intensity observed in STELLAR-303 and earlier datasets, Peters said Exelixis uses extensive pharmacokinetic modeling and exposure-response work to inform dose selection. He said the company considers tumor sensitivity, line of therapy and combination partners rather than assuming one dose should apply across all indications.
Peters said Exelixis is applying lessons from cabozantinib development to zanzalintinib. He described the goal as optimizing clinical benefit-risk by indication and combination, with the broader objective of running studies capable of changing standards of care.
Renal Cell Carcinoma Studies Aim to Define Future Use
In renal cell carcinoma, Peters discussed STELLAR-304, a study of zanzalintinib plus nivolumab in non-clear cell RCC. He said the lack of large randomized data in non-clear cell RCC is notable, and current guideline use is largely informed by smaller, single-arm studies.
Exelixis designed STELLAR-304 to test the regimen against an active standard of care and potentially generate what Peters called “level 1 evidence.” Top-line data are expected later this year, according to the discussion.
Peters also discussed Exelixis’ collaborations with Merck, including LITESPARK-033 and LITESPARK-034. He said the company is thinking about how RCC treatment may evolve, describing cabozantinib as “the TKI of the 2020s” and zanzalintinib as a candidate to become “the TKI of the 2030s.”
For LITESPARK-034, Peters said recent LITESPARK-011 data suggest HIF-VEGF TKI combinations can play a role in the RCC treatment journey. He said Exelixis aims to determine whether an optimized TKI such as zanzalintinib can improve on that approach.
For LITESPARK-033, which evaluates belzutifan and zanzalintinib after adjuvant immunotherapy, Peters said the industry has seen challenges with immunotherapy retreatment across tumor types. He said Exelixis expects adjuvant pembrolizumab use to expand over time, particularly after survival benefit data, and wants to help define treatment options for patients who progress after adjuvant checkpoint therapy.
Other Pipeline Updates
Willey also asked about STELLAR-311, a phase II/III study of single-agent zanzalintinib versus everolimus as first TKI therapy in neuroendocrine tumors. Peters did not provide specifics on the phase II/III gating criteria, but said the design is intended to improve efficiency and assess whether the study is likely to succeed while continuing enrollment.
Beyond zanzalintinib, Peters said Exelixis has several early-stage programs, including antibody-drug conjugates and other biotherapeutics. He said the company does not plan to release small, immature datasets, instead waiting for more stable results that can support investment decisions.
“If any of those early stage programs aren’t going to potentially define a new standard of care, we’ll move on to the next thing,” Peters said. He added that Exelixis intends to prioritize programs rigorously and present data when it has a robust enough dataset to explain why the company is advancing or discontinuing an asset.
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.
