Gilead and Arcus Announce Anti-TIGIT Domvanalimab Plus Zimberelimab and Chemotherapy Exceeded One Year of Median Progression-Free Survival as a First-Line Treatment for Upper GI Cancers
Gilead Sciences and Arcus Biosciences announced positive results from the Phase 2 EDGE-Gastric study, which evaluated the combination of domvanalimab, zimberelimab, and chemotherapy in treating upper GI cancers. Results showed a median progression-free survival (PFS) of over one year, with a 12-month PFS rate of nearly 60%. The regimen demonstrated consistent objective response rates and was well-tolerated, with no unexpected safety signals. These findings support the ongoing Phase 3 STAR-221 study, which aims to confirm these results and potentially bring the first anti-TIGIT combination therapy to market for upper GI cancers. Data will be presented at the ASCO Annual Meeting.
- Median progression-free survival (PFS) exceeded one year.
- Nearly 60% of patients achieved 12-month PFS.
- Confirmed objective response rate (ORR) was 58.5%.
- Domvanalimab plus zimberelimab and chemotherapy regimen was well-tolerated.
- No unexpected safety signals were observed.
- Results support the ongoing Phase 3 STAR-221 study.
- Only 41 patients were enrolled in the study, limiting the robustness of the data.
- Progressive disease was confirmed in 4.9% of patients.
- Infusion-related reactions were observed in 19.5% of subjects.
Insights
The latest results from Gilead Sciences and Arcus Biosciences regarding their Phase 2 EDGE-Gastric study are promising from a financial investment perspective. Domvanalimab plus zimberelimab and chemotherapy showed a median progression-free survival (PFS) of , which is significant when compared to historical benchmarks for anti-PD-1 plus chemotherapy alone. This positive data could potentially make this combination a first-in-class anti-TIGIT treatment for upper GI cancers, leading to a strong competitive advantage if approved.
Financial implications: The Phase 3 STAR-221 study is important and its potential success could significantly boost the companies' market positions and stock prices. Investors should closely monitor updates on this study’s progress.
Short-term outlook: The immediate market reaction could be positive, given the noteworthy median PFS results, reinforcing investor confidence in Gilead’s and Arcus's oncology pipelines.
Long-term perspective: If the Phase 3 trial confirms these findings, it could lead to regulatory approval, expanding the companies' portfolios and driving revenue growth. Investors should also note the safety profile, as no unexpected safety signals were observed, which strengthens the likelihood of regulatory success.
From a clinical standpoint, the updated data on domvanalimab plus zimberelimab and chemotherapy are quite compelling. The observed median PFS of and a 12-month PFS rate of
Clinical implications: The results support further investigation in the Phase 3 STAR-221 study, which, if successful, could offer a substantial new treatment option for patients with upper GI cancers, who currently have limited effective therapies. These findings align with the ongoing trend of utilizing checkpoint inhibitors to enhance immune response against tumors.
The lack of unexpected safety signals is reassuring, suggesting that the combination therapy can be administered with manageable side effects, an essential consideration for patient quality of life.
The announcement of the positive Phase 2 results for domvanalimab plus zimberelimab and chemotherapy in upper GI cancers is pivotal for Gilead and Arcus. This therapeutic combination's potential to become the first anti-TIGIT treatment approved for these cancers positions both companies favorably in the oncology market.
Market potential: If the Phase 3 STAR-221 study confirms these findings, the combination therapy could address a significant unmet need, potentially capturing a substantial market share in the upper GI cancer segment. Given the competitive landscape in oncology, this would enhance the firms' competitive edge and possibly lead to partnerships or acquisitions in the future.
Strategically, these findings help in solidifying Gilead's and Arcus Biosciences' reputations as innovators in cancer treatment, potentially driving further investment and interest in their oncology pipelines. The ongoing collaboration between the two companies also signifies a robust strategic partnership, likely to yield additional novel treatments.
– Data Support the Ongoing Phase 3 STAR-221 Study of Domvanalimab Plus Zimberelimab and Chemotherapy, Potentially the First Anti-TIGIT Combination to Market for These Cancers –
– Results will be Presented Today During an Oral Session at the ASCO Annual Meeting –
“I am encouraged to see that patients treated with domvanalimab plus zimberelimab and chemotherapy had a median progression-free survival beyond one year, which exceeds the historical benchmarks for anti-PD-1 plus chemotherapy alone,” said Dr. Janjigian. “Notably, nearly
At data cutoff (DCO, March 12, 2024), safety and efficacy were evaluated in all patients enrolled and treated (n=41). With a median time on treatment of 49.4 weeks (range: 0.4 - 79.4 weeks), the domvanalimab plus zimberelimab and chemotherapy regimen demonstrated sustained improvement across efficacy measures, including in those patients who have low PD-L1 expression.
Summary of efficacy results: |
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Endpoint |
Overall*
|
PD-L1-high
|
PD-L1-low
|
Progression-Free Survival (PFS) |
|
|
|
Median in Months ( |
12.9 mos (9.8, 13.8) |
13.8 mos (11.3, NE) |
11.3 mos (5.5, 13.8) |
12-month PFS Rate ( |
|
|
|
Objective Response Rate (ORR) per RECIST v1.1 |
|
|
|
Confirmed ORR ( |
|
|
|
Complete Response |
3 ( |
1 ( |
1 ( |
Partial Response |
21 ( |
10 ( |
11 ( |
Stable Disease |
14 ( |
5 ( |
9 ( |
Progressive Disease Confirmed |
2 ( |
0 |
2 ( |
Not Evaluable** |
1 ( |
0 |
1 ( |
Median Duration of Response (DOR) in Months |
12.4 mos (9.9, NE) |
NE (11.5, NE) |
10.2 mos (4.0, 12.4) |
*One subject with no tissue available for central PD-L1 testing. From local lab results, the subject is PD-L1 low via 22-C3 assay. This subject achieved confirmed complete response. |
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** One subject has no post baseline scans |
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CI: confidence interval |
|||
NE: not evaluable |
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TAP: tumor area positivity |
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No unexpected safety signals were observed at the time of DCO. The domvanalimab plus zimberelimab and chemotherapy regimen was generally well tolerated and showed an overall safety profile consistent with the known safety profiles of each individual molecule to date. Infusion-related reactions were observed in
The updated data from Arm A1 of the Phase 2 EDGE-Gastric study support the ongoing Phase 3 STAR-221 study, in unresectable or metastatic upper GI cancers, which is expected to complete enrollment mid-year 2024.
Domvanalimab and zimberelimab are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use of these molecules, and their safety and efficacy for the treatment of gastrointestinal cancers have not been established.
About the EDGE-Gastric Study
The ongoing, multi-arm, multi-cohort global Phase 2 EDGE-Gastric trial (NCT05329766) is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab and the anti-PD-1 monoclonal antibody zimberelimab in patients with locally advanced unresectable or metastatic gastric (G), gastroesophageal junction (GEJ) or esophageal (E) adenocarcinoma. Patients in Arm A1, with previously untreated G/GEJ/E adenocarcinoma, received 1600 mg of domvanalimab intravenously (IV) every four weeks (Q4W) plus 480 mg of zimberelimab IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus + 2400 mg/m2 continuous 46-48-hour IV infusion) every two weeks.
About Domvanalimab
Domvanalimab is the first and most clinically advanced Fc-silent investigational monoclonal antibody that is specifically designed with Fc-silent properties to block and bind to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a checkpoint receptor on immune cells that acts as a brake on the anticancer immune response. By binding to TIGIT with Fc-silent properties, domvanalimab is believed to work by freeing up immune-activating pathways and activate immune cells to attack and kill cancer cells without depleting the peripheral regulatory T cells important in avoiding immune-related toxicity.
Combined inhibition of both TIGIT and programmed cell death protein-1 (PD-1) is believed to significantly enhance immune cell activation, as these checkpoint receptors play distinct, complementary roles in anti-tumor activity. Domvanalimab is being evaluated in combination with anti-PD-1 monoclonal antibodies, including zimberelimab, as well as other investigational cancer immunotherapies and A2a/A2b adenosine receptor antagonist etrumadenant, in multiple ongoing and planned early and late-stage clinical studies in various tumor types.
About Zimberelimab
Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the antitumor activity of T cells. Zimberelimab has demonstrated high affinity, selectivity and potency in various tumor types.
Zimberelimab is being evaluated in the
Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights for zimberelimab in greater
About Arcus Biosciences
Arcus Biosciences is a clinical-stage, global biopharmaceutical company developing differentiated molecules and combination medicines for people with cancer. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of first- or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has expedited the development of multiple investigational medicines into clinical studies, including new combination approaches that target TIGIT, PD-1, the adenosine axis (CD73 and dual A2a/A2b receptor), HIF-2a, CD39 and AXL. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in
Arcus Forward-Looking Statements
This press release contains forward-looking statements. All statements regarding events or results to occur in the future contained herein are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, the statements in Dr. Janjigian’s quote and statements regarding: whether data and results from the EDGE-Gastric study reinforces our confidence in our Phase 3 STAR-221 study and the potential of this regimen to address a high unmet need for people with upper GI cancers; the potential for domvanalimab in combination with zimberelimab and chemotherapy to be first anti-TIGIT combination to market for upper GI cancers; and the timing of upcoming milestones. All forward-looking statements involve known and unknown risks and uncertainties and other important factors that may cause Arcus’s actual results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to risks associated with: interim data not being replicated in future studies evaluating the same investigational molecules or regimen; the unexpected emergence of adverse events or other undesirable side effects in Arcus’s investigational products, including domvanalimab and zimberelimab; risks associated with the manufacturing or supplying product for such clinical trials; uncertainties in timelines associated with the conduct of clinical studies and with respect to the regulatory application process; Arcus’s dependence on the collaboration with Gilead for the successful development and commercialization of its optioned molecules; difficulties associated with the management of the collaboration activities with our strategic partners or expanded clinical programs; changes in the competitive landscape for Arcus’s programs; and the inherent uncertainty associated with pharmaceutical product development and clinical trials. Risks and uncertainties facing Arcus are described more fully in the “Risk Factors” section of Arcus’s most recent periodic report filed with the
Gilead Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving domvanalimab and zimberelimab (such as the EDGE-Gastric and STAR-221 studies); uncertainties relating to regulatory applications and related filing and approval timelines, and the risk that any such approvals, if granted, may be subject to significant limitations on use; the possibility that Gilead may make a strategic decision to discontinue development of domvanalimab and zimberelimab for indications that are currently under evaluation and, as a result, these programs may never be successfully commercialized for such indications; the risk that Gilead may not realize the potential benefits of its collaboration with Arcus or its other investments in oncology; difficulties or unanticipated expenses in connection with the collaboration and the potential effects on Gilead’s revenues and earnings; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, as filed with the
Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.
Arcus name and logo are trademarks of Arcus Biosciences, Inc.
For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on X/Twitter (@Gilead Sciences) and LinkedIn (@Gilead-Sciences).
Dr. Janjigian has served as a consultant to Arcus Biosciences; she has not been paid for any media work.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240601477420/en/
Meaghan Smith, Gilead Media
public_affairs@gilead.com
Jacquie Ross, Gilead Investors
investor_relations@gilead.com
Pia Eaves, Arcus Investors
peaves@arcusbio.com, (617) 459-2006
Holli Kolkey, Arcus Media
hkolkey@arcusbio.com, (650) 922-1269
Source: Arcus Biosciences
FAQ
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