Exelixis Announces Encouraging Results From Phase 1b/2 STAR 001 Trial Evaluating Samzalintinib Alone Or In Combination With An Immune Checkpoint Inhibitor In Metastatic Colorectal Cancer At ASCO GI

“In a subgroup analysis of patients without liver metastases, the addition of atezolizumab to zanzalintinib led to increased progression-free survival and overall survival”

ALAMEDA, Calif.-(Business Wire)–Exelixis, Inc. (NASDAQ: EXEL) today announced the results of an expansion arm of the Phase 1b/2 STAR trial evaluating samzalintinib alone or in combination with atezolizumab (Tecentriq ® ) in patients with previously treated metastatic colorectal cancer (CRC). The findings will be presented during Poster Session C: Colon, Rectal, and Anal Cancer, at 7:00 AM PT on January 25 at the American Society of Clinical Oncology 2025 Gastrointestinal Cancers Symposium (ASCO GI 2025).

This cohort of the Stellar-001 trial included 107 patients randomized 1:1 to receive single-agent zanzalintinib or zanzalintinib in combination with atezolizumab. Patients had unresectable, locally advanced or metastatic disease Rac Wild-type CRC that is not bio-microsatellite instability high or mismatched deficiency. The median number of prior lines of therapy was 3.0 for patients treated with sanzalintinib and 2.5 for patients treated with sanzalintinib in combination with atezolizumab. Thirty-two percent and 31% of patients had no liver metastases in the initial scan.

Both progression-free survival (PFS) and overall survival (OS) were numerically improved by adding atezolizumab to zanzalintinib. Detailed efficacy results for the overall population and subgroup analysis of patients without liver metastases are provided in Table 1 below.

In a biomarker analysis, a PD-L1 composite positive score greater than 1 was associated with improved PFS and OS in patients treated with zanzalintinib in combination with atezolizumab alone versus zanzalintinib alone.

This arm of the Stellar-001 trial is intended to inform the contribution of atezolizumab to zanzalintinib in patients with previously treated metastatic colorectal cancer, said Amy Peterson, MD. Med., Executive Vice President, Product Development & Medical (Tase 🙂 jobs and Chief Medical Officer, Exelixis (NASDAQ :). Data from this randomized expansion cohort support our decision to initiate STAR-303 evaluating zanzalintinib in combination with atezolizumab compared with regorafenib in patients with metastatic colorectal cancer, which completed enrollment in August 2024, and we anticipate data from that trial in the second half of 2025, depending on the rate of study events.

Detailed safety results for the overall population are provided in Table 2 below. Grade 3/4 treatment-related adverse events (AEs) occurred in 40% of patients receiving zanzalintinib alone and 48% of patients receiving zanzalintinib in combination with atezolizumab. One grade 5 AE occurred in each group, both of which were also determined by investigators related to the study disease. Zanzalintinib was discontinued in 19% of patients who received zanzalintinib alone, and 30% of patients who received zanzalintinib in combination with atezolizumab. Treatment-related AEs leading to discontinuation of either drug occurred in 8% and 19% of patients.

About the stellar 001
Stellar-001 (NCT03845166) is a global open-label phase 1b/2 open-label phase 1B/2 study as a single agent or in combination with atezolizumab in patients with unresectable locally advanced or metastatic solid tumors. The trial was divided into two parts: a dose escalation phase and an expansion cohort phase. Expansion cohorts evaluating zanzalintinib (100 mg) as a single agent or in combination with atezolizumab also include patients with clear cell renal cell carcinoma (RCC), non-small cell RCC, hormone-positive, and HER-2-negative breast cancer. and castration-resistant prostate cancer. More information about the trial is available at ClinicalTrials.gov.

About star-303
A global phase 3 pivotal study, Stellar-303, is evaluating zanzalintinib (100 mg) in combination with atezolizumab compared with regorafenib in patients with metastatic, refractory non-microsatellite unstable or non-discordant specific deficiency. The primary endpoint in the study is OS in patients without active liver metastases. If OS is positive in the population of patients without liver metastases, the study will evaluate OS in an intention-to-treat population that includes patients with and without liver metastases and without liver metastases. The study ended enrollment in the third quarter of 2024, and preliminary results are expected in the second half of 2025, depending on the rate of study. More information about the trial is available at ClinicalTrials.gov.

About zanzalintinib
Zanzalintinib is a third-generation oral tyrosine kinase inhibitor that inhibits the activity of receptor tyrosine kinases involved in cancer growth and spread, including VEGF receptors, MET, AXL, and MER. These receptor tyrosine kinases are involved in both normal cellular function and pathological processes such as oncogenesis, metastasis, tumor angiogenesis, and resistance to multiple therapies, including immune checkpoint inhibitors. With Zanzalintinib, Exelixis sought to build on its extensive experience with the target profile of Cabozantinib, the company’s lead medicine, while improving key characteristics, including pharmacokinetic half-life. Zanzalintinib is currently being developed for the treatment of advanced solid tumors, including genitourinary, colorectal, and head and neck cancers. A pivotal phase 3 trial evaluating Zanzalintinib compared with everolimus as first-line oral therapy in patients with advanced neuroendocrine tumors (NETs), regardless of site of origin, is expected in the first half of 2025.

About CRC
Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths in the US1, about 154,000 new cases in the US will be diagnosed in the US with about 53,000 expected deaths from the disease in 2025.1. 65-74 and is more common in men and in people of non-Hispanic American Indian/Alaskan descent. 2 Almost a quarter of colorectal cancer cases are diagnosed in the metastatic stage, at which point the five-year survival rate is only 15.7%.2

About exelixis
Exelixis is a globally ambitious oncology company innovating new generation drugs and regimens at the forefront of cancer care. Driven by drug discovery and development excellence, we are rapidly evolving our product portfolio to target a growing range of tumor types and indications with our clinically differentiated pipeline of small molecules, anti-drug conjugates and other biotherapeutics. This comprehensive approach leverages decades of strong investment in our science and partnerships to advance our investigational programs and expand the impact of our lead commercial product, CaboMetyx ® (Cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com, follow @Exelixisinc on X (Twitter), like Exelixis, Inc. on Facebook (NASDAQ 🙂 and follow the following Exelixis on LinkedIn.

Forward-looking statements
This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of data from Stellar-001 at ASCO GI 2025; Expectation for initial clinical data readouts from Stellar-303 in the second half of 2025, depending on study event rates; Therapeutic potential of zanzalintinib, alone and in combination with etezolizumab, in patients with metastatic CRC; and Exelixis’ scientific quest to create transformational treatments that give more patients hope for the future. All statements relating to expectations, projections or other characteristics of future events or circumstances are forward-looking statements and are based on Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: availability of data at the reference time; the complexities and unpredictability of the regulatory review and approval process in the US and elsewhere; Exelixis’ continued compliance with applicable legal and regulatory requirements; Potential failure of Zanzalintinib, alone and in combination with atezolizumab, to demonstrate safety and/or efficacy in Stellar-001, Stellar-303 and in a future clinical trial; Unanticipated concerns that may arise as a result of the occurrence of adverse safety events or additional analyzes of data from clinical trials evaluating zanzalintinib; costs of conducting clinical trials; Exelixis’ dependence on third-party suppliers for the development, manufacture and supply of zanzalintinib; Exelixis’ ability to protect its intellectual property rights; market competition; changes in economic and business conditions; and other factors affecting Exelixis and its development programs described in detail from time to time in accordance with the risk factors caption in Exelixis’ most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’ future filings with securities and exchange commission. All statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

Exelixis, the Exelixis logo and CaboMetyx are registered US trademarks of Exelixis.

Tecentriq (Atezolizumab) is a registered trademark of Genentech, a member of the Roche group.

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1 Key statistics for colorectal cancer. ACS. Available at: https://www.cancer.org/cancer/types/colon-rectal-cancer/about/key-statistics.html. Accessed January 2025.
2 Cancer Stat Facts: Colorectal Cancer. Look. Available at: https://seer.cancer.gov/statfacts/html/colorect.html. Accessed January 2025.

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Investors contact:
Susan Hubbard
EVP, public affairs and
Investor relations
Exelixis, Inc.
650-837-8194
shubbard@exelixis.com

Media contact:
Stekkie Millman
Senior Director, Public Affairs
Exelixis, Inc.
650-837-7187
smillman@exelixis.com

Source: Exelixis, Inc.