– In a subgroup analysis of patients without
liver metastases, adding atezolizumab to zanzalintinib led to
enhanced progression-free survival and overall survival –
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.
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version on businesswire.com: https://www.businesswire.com/news/home/20250124233353/en/
Investors Contact: Susan Hubbard EVP, Public Affairs and
Investor Relations Exelixis, Inc. 650-837-8194
shubbard@exelixis.com
Media Contact: Stekki Millman Senior Director, Public
Affairs Exelixis, Inc. 650-837-7187 smillman@exelixis.com
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