Regorafenib

– In a subgroup analysis of patients without liver metastases, adding atezolizumab to zanzalintinib led to enhanced progression-free survival and overall survival – ALAMEDA, CA, USA I January 25, 2025 I Exelixis, Inc. (Nasdaq: EXEL) today announced results from an expansion cohort of the phase 1b/2 STELLAR-001 trial evaluating zanzalintinib 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: Cancers of the Colon, Rectum and Anus, at 7:00 a.m. 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 RAS wild-type CRC that was non-microsatellite instability-high or non-mismatch repair-deficient. The median number of prior lines of therapy was 3.0 for patients treated with zanzalintinib alone and 2.5 for patients treated with zanzalintinib in combination with atezolizumab. Thirty-two percent and 31% of patients did not have liver metastases in baseline scans, respectively. Both progression-free survival (PFS) and overall survival (OS) were numerically improved by the addition of atezolizumab to zanzalintinib. Detailed efficacy results of the overall population and the subgroup analysis of patients without liver metastases are in Table 1 below. In a biomarker analysis, a PD-L1 combined positive score greater than 1 was associated with improved PFS and OS in patients treated with zanzalintinib in combination with atezolizumab versus zanzalintinib alone. “This cohort of the STELLAR-001 trial was designed to inform the contribution of atezolizumab to zanzalintinib in patients with previously treated metastatic colorectal cancer,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “Data from this randomized expansion cohort reaffirms our decision to initiate STELLAR-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, dependent on study event rates.” Detailed safety results for the overall population are 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 treatment-related AE occurred in each group, both of which were also determined by investigator as related to the disease under study. Zanzalintinib was discontinued in 19% of patients receiving zanzalintinib alone and 30% of patients receiving zanzalintinib in combination with atezolizumab. Treatment-related AEs leading to discontinuation of any drug occurred in 8% and 19% of patients, respectively. About STELLAR-001 STELLAR-001 (NCT03845166) is a global, open-label phase 1b/2 study of zanzalintinib as a single agent or in combination with atezolizumab in patients with inoperable locally advanced or metastatic solid tumors. The trial is divided into two parts: a dose-escalation stage and an expansion cohort stage. The 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-clear cell RCC, breast cancer that is hormone receptor-positive and HER-2 negative and castration-resistant prostate cancer. More information about the trial is available at ClinicalTrials.gov . About STELLAR-303 The 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 instability-high or non-mismatch repair-deficient CRC. 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 the intent-to-treat population that includes patients with and without liver metastases. The study completed enrollment in the third quarter of 2024, and preliminary results are expected in the second half of 2025, dependent on study event rates. 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 implicated in cancer growth and spread, including VEGF receptors, MET, AXL and MER. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and resistance to multiple therapies, including immune checkpoint inhibitors. With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship 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 phase 3 pivotal trial evaluating zanzalintinib compared with everolimus as a first oral therapy in patients with advanced neuroendocrine tumors (NET), regardless of site of origin, is expected to be initiated 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 U.S. 1 Approximately 154,000 new cases will be diagnosed in the U.S. with around 53,000 expected deaths from the disease in 2025. 1 Colorectal cancer is most frequently diagnosed among people aged 65-74 and is more common in men and in people of non-Hispanic American Indian/Alaska Native descent. 2 Nearly a quarter of colorectal cancer cases are diagnosed at the metastatic stage, at which point the five-year survival rate is just 15.7%. 2 About Exelixis Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship 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 and follow Exelixis on LinkedIn. 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. SEER. Available at: https://seer.cancer.gov/statfacts/html/colorect.html. Accessed January 2025 . SOURCE: Exelixis

ALAMEDA, Calif.--( BUSINESS WIRE )-- Exelixis, Inc. (Nasdaq: EXEL) today announced results from an expansion cohort of the phase 1b/2 STELLAR-001 trial evaluating zanzalintinib 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: Cancers of the Colon, Rectum and Anus, at 7:00 a.m. 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 RAS wild-type CRC that was non-microsatellite instability-high or non-mismatch repair-deficient. The median number of prior lines of therapy was 3.0 for patients treated with zanzalintinib alone and 2.5 for patients treated with zanzalintinib in combination with atezolizumab. Thirty-two percent and 31% of patients did not have liver metastases in baseline scans, respectively. Both progression-free survival (PFS) and overall survival (OS) were numerically improved by the addition of atezolizumab to zanzalintinib. Detailed efficacy results of the overall population and the subgroup analysis of patients without liver metastases are in Table 1 below. TABLE 1 Zanzalintinib alone Zanzalintinib + atezolizumab Overall population Patients, n 53 54 Median follow-up, months 19.2 18.9 Median PFS, months 3.0 4.0 PFS HR (95% CI) 0.65 (0.42-0.99) Median OS, months 11.1 11.7 OS HR (95% CI) 0.89 (0.56-1.42) ORR, % 1.9 7.4 Partial response, n 1 4 Patients without liver metastases Patients, n 17 17 Median PFS, months 3.3 8.2 PFS HR (95% CI) 0.37 (0.15-0.91) Median OS, months 21.1 18.5 OS HR (95% CI) 0.74 (0.27-2.04) 6-month survival rate, % 64.7 87.8 12-month survival rate, % 52.3 62.7 ORR, % 5.9 18.0 Partial response, n 1 3 CI: confidence interval; HR: hazard ratio; ORR: objective response rate; OS: overall survival; PFS: progression-free survival. In a biomarker analysis, a PD-L1 combined positive score greater than 1 was associated with improved PFS and OS in patients treated with zanzalintinib in combination with atezolizumab versus zanzalintinib alone. “ This cohort of the STELLAR-001 trial was designed to inform the contribution of atezolizumab to zanzalintinib in patients with previously treated metastatic colorectal cancer,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “ Data from this randomized expansion cohort reaffirms our decision to initiate STELLAR-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, dependent on study event rates.” Detailed safety results for the overall population are 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 treatment-related AE occurred in each group, both of which were also determined by investigator as related to the disease under study. Zanzalintinib was discontinued in 19% of patients receiving zanzalintinib alone and 30% of patients receiving zanzalintinib in combination with atezolizumab. Treatment-related AEs leading to discontinuation of any drug occurred in 8% and 19% of patients, respectively. TABLE 2 Zanzalintinib alone Zanzalintinib + atezolizumab Any Grade Grade 3/4 Any Grade Grade 3/4 Most Common TRAE, % Nausea 36 6 54 0 Diarrhea 49 8 52 9 Fatigue 21 4 43 11 Hypertension 30 13 19 7 Other TRAE, % Proteinuria 17 0 13 0 Palmar-plantar erythrodysesthesia 11 0 6 0 Stomatitis 2 2 6 0 TRAE: treatment-related adverse event About STELLAR-001 STELLAR-001 (NCT03845166) is a global, open-label phase 1b/2 study of zanzalintinib as a single agent or in combination with atezolizumab in patients with inoperable locally advanced or metastatic solid tumors. The trial is divided into two parts: a dose-escalation stage and an expansion cohort stage. The 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-clear cell RCC, breast cancer that is hormone receptor-positive and HER-2 negative and castration-resistant prostate cancer. More information about the trial is available at ClinicalTrials.gov . About STELLAR-303 The 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 instability-high or non-mismatch repair-deficient CRC. 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 the intent-to-treat population that includes patients with and without liver metastases. The study completed enrollment in the third quarter of 2024, and preliminary results are expected in the second half of 2025, dependent on study event rates. 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 implicated in cancer growth and spread, including VEGF receptors, MET, AXL and MER. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and resistance to multiple therapies, including immune checkpoint inhibitors. With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship 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 phase 3 pivotal trial evaluating zanzalintinib compared with everolimus as a first oral therapy in patients with advanced neuroendocrine tumors (NET), regardless of site of origin, is expected to be initiated 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 U.S. 1 Approximately 154,000 new cases will be diagnosed in the U.S. with around 53,000 expected deaths from the disease in 2025. 1 Colorectal cancer is most frequently diagnosed among people aged 65-74 and is more common in men and in people of non-Hispanic American Indian/Alaska Native descent. 2 Nearly a quarter of colorectal cancer cases are diagnosed at the metastatic stage, at which point the five-year survival rate is just 15.7%. 2 About Exelixis Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship 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 and follow 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; the expectation for initial clinical data readouts from STELLAR-303 in the second half of 2025, dependent on study event rates; the therapeutic potential of zanzalintinib, both alone and in combination with atezolizumab, in patients with metastatic CRC; and Exelixis’ scientific pursuit to create transformational treatments that give more patients hope for the future. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon 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: the availability of data at the referenced times; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis’ continuing compliance with applicable legal and regulatory requirements; the potential failure of zanzalintinib, both alone and in combination with atezolizumab to demonstrate safety and/or efficacy in STELLAR-001, STELLAR-303 and in future clinical testing; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating zanzalintinib; the costs of conducting clinical trials; Exelixis’ dependence on third-party vendors 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 detailed from time to time under the caption “Risk Factors” in Exelixis’ most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’ future filings with the Securities and Exchange Commission. All forward-looking 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 U.S. trademarks of Exelixis. TECENTRIQ (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group. _________________ 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. SEER. Available at: https://seer.cancer.gov/statfacts/html/colorect.html . Accessed January 2025.