Arcus Biosciences Announces that Domvanalimab Plus Zimberelimab Improved Overall Survival in ARC-10, a Randomized Study in Patients with PD-L1-High Non-Small Cell Lung Cancer
Arcus Biosciences (NYSE:RCUS) announced positive results from Part 1 of ARC-10 study evaluating domvanalimab plus zimberelimab (DZ) in non-small cell lung cancer patients. The combination demonstrated a 36% reduction in death risk compared to zimberelimab alone, with median overall survival not yet reached versus 24.4 months for zimberelimab. The DZ combination showed improved progression-free survival of 11.5 months versus 6.2 months, and higher objective response rate of 44.7% versus 35%. Treatment-related adverse events leading to discontinuation were lower in the DZ group (10.5%) compared to chemotherapy (23.5%).
Arcus Biosciences (NYSE:RCUS) ha annunciato risultati positivi dalla Parte 1 dello studio ARC-10 che valuta domvanalimab più zimberelimab (DZ) in pazienti con carcinoma polmonare non a piccole cellule. La combinazione ha dimostrato una riduzione del 36% del rischio di morte rispetto a zimberelimab da solo, con la mediana di sopravvivenza globale non ancora raggiunta rispetto a 24,4 mesi per zimberelimab. La combinazione DZ ha mostrato un miglioramento della sopravvivenza libera da progressione di 11,5 mesi rispetto a 6,2 mesi, e un tasso di risposta obiettiva più alto del 44,7% rispetto al 35%. Gli eventi avversi legati al trattamento che hanno portato a interruzioni sono stati inferiori nel gruppo DZ (10,5%) rispetto alla chemioterapia (23,5%).
Arcus Biosciences (NYSE:RCUS) anunció resultados positivos de la Parte 1 del estudio ARC-10 que evalúa domvanalimab más zimberelimab (DZ) en pacientes con carcinoma de pulmón no microcítico. La combinación demostró una reducción del 36% en el riesgo de muerte en comparación con zimberelimab solo, con una mediana de supervivencia global aún no alcanzada frente a 24,4 meses para zimberelimab. La combinación DZ mostró una mejora en la supervivencia libre de progresión de 11,5 meses frente a 6,2 meses, y una tasa de respuesta objetiva más alta del 44,7% frente al 35%. Los eventos adversos relacionados con el tratamiento que llevaron a la interrupción fueron menores en el grupo DZ (10,5%) en comparación con la quimioterapia (23,5%).
Arcus Biosciences (NYSE:RCUS)는 비소세포 폐암 환자에서 domvanalimab과 zimberelimab (DZ)의 효과를 평가한 ARC-10 연구 1부의 긍정적인 결과를 발표했습니다. 이 조합은 zimberelimab 단독 치료에 비해 사망 위험을 36% 감소시킨 것으로 나타났으며, zimberelimab의 24.4개월과 비교하여 중간 전체 생존 기간은 아직 도달하지 않았습니다. DZ 조합은 6.2개월과 비교하여 11.5개월의 더 나은 무진행 생존 기간을 보였고, 35%에 비해 44.7%의 더 높은 객관적 반응률을 나타냈습니다. 치료와 관련된 부작용으로 인한 치료 중단 비율은 DZ 그룹에서 10.5%로 화학요법의 23.5%에 비해 낮았습니다.
Arcus Biosciences (NYSE:RCUS) a annoncé des résultats positifs de la Partie 1 de l'étude ARC-10 évaluant domvanalimab plus zimberelimab (DZ) chez des patients atteints de cancer du poumon non à petites cellules. La combinaison a montré une réduction de 36 % du risque de décès par rapport à zimberelimab seul, avec une survie globale médiane encore non atteinte contre 24,4 mois pour zimberelimab. La combinaison DZ a montré une amélioration de la survie sans progression de 11,5 mois contre 6,2 mois, et un taux de réponse objective plus élevé de 44,7 % contre 35 %. Les événements indésirables liés au traitement entraînant l'arrêt du traitement étaient moins fréquents dans le groupe DZ (10,5 %) comparé à la chimiothérapie (23,5 %).
Arcus Biosciences (NYSE:RCUS) gab positive Ergebnisse aus Teil 1 der ARC-10-Studie bekannt, die domvanalimab plus zimberelimab (DZ) bei Patienten mit nicht-kleinzelligem Lungenkrebs bewertet. Die Kombination zeigte eine 36%ige Reduktion des Sterberisikos im Vergleich zu zimberelimab allein, wobei das mediane Überleben noch nicht erreicht wurde im Vergleich zu 24,4 Monaten für zimberelimab. Die DZ-Kombination zeigte eine verbesserte progressionsfreie Überlebenszeit von 11,5 Monaten im Vergleich zu 6,2 Monaten und eine höhere objektive Ansprechrate von 44,7% im Vergleich zu 35%. Die behandlungsassoziierten unerwünschten Ereignisse, die zur Unterbrechung führten, waren in der DZ-Gruppe (10,5%) im Vergleich zur Chemotherapie (23,5%) geringer.
- 36% reduction in death risk with DZ combination compared to zimberelimab alone
- Improved progression-free survival: 11.5 months for DZ vs 6.2 months for zimberelimab
- Higher objective response rate: 44.7% for DZ vs 35% for zimberelimab
- Lower treatment discontinuation rate: 10.5% for DZ vs 23.5% for chemotherapy
- Lower Grade ≥3 treatment-related adverse events: 21.1% for DZ vs 47.1% for chemotherapy
- One treatment-related death reported in the DZ group (sudden death)
Insights
The clinical trial results for domvanalimab plus zimberelimab show significant promise in NSCLC treatment. The 36% reduction in death risk (HR=0.64) compared to zimberelimab alone is clinically meaningful. The combination therapy demonstrated superior outcomes across key metrics:
- Median overall survival not yet reached vs 24.4 months for zimberelimab alone
- Higher 12-month survival rate (
68% vs57% ) - Improved progression-free survival (11.5 months vs 6.2 months)
- Better objective response rate (
44.7% vs35% )
These positive trial results significantly strengthen Arcus's market position in the competitive immunotherapy landscape. The data demonstrates superiority over both standard chemotherapy and single-agent immunotherapy, potentially positioning domvanalimab plus zimberelimab as a leading first-line treatment option. The partnership with Gilead Sciences adds credibility and commercialization potential. The improved survival benefits combined with better tolerability could drive substantial market adoption, particularly given the large addressable market for NSCLC. This could translate into significant revenue potential, considering that leading lung cancer immunotherapies generate multi-billion dollar annual sales.
- Domvanalimab plus zimberelimab was associated with greater progression-free survival, overall survival, and objective response rate compared with those of zimberelimab or chemotherapy
-
A
36% reduction in risk of death (HR=0.64) was observed for domvanalimab plus zimberelimab compared to zimberelimab alone; zimberelimab reached a median overall survival of two years while the median overall survival for domvanalimab plus zimberelimab was not reached
-
Treatment-related adverse events leading to treatment discontinuation were low (
10.5% ) for the combination of domvanalimab and zimberelimab relative to chemotherapy (23.5% )
- Arcus will discuss these results on its earnings call at 2:00 PM PT / 5:00 PM ET Wednesday, November 6, 2024
“Domvanalimab plus zimberelimab demonstrated a meaningful improvement in overall survival compared to zimberelimab alone, with a
“These are the first results demonstrating an improvement in overall survival reported for domvanalimab and zimberelimab,” said Dimitry Nuyten, M.D., Ph.D., chief medical officer of Arcus. “They add to the growing body of evidence that domvanalimab, an Fc-silent anti-TIGIT antibody, may have a differentiated efficacy, safety and tolerability profile relative to published data from studies with Fc-enabled anti-TIGIT antibodies.”
At the time of data cutoff (DCO, May 17, 2024), 98 patients were randomized and 95 received treatment in Part 1 of the study. The median follow-up was 24.5 months, and as of the DCO, 22 patients remained on treatment (DZ, n=11; Z, n=10; chemo, n=1). Patient baseline demographics were generally balanced across the arms, with a slight imbalance of more patients with adenocarcinoma, ECOG status 0, and brain metastasis favoring the chemotherapy arm. A summary of efficacy results is below.
Endpoint |
DZ (n=38) |
Z (n=40) |
Platinum-Doublet Chemo* (n=17) |
Overall Survival (OS) |
|||
Median, months ( |
NR (13.7-NE) |
24.4 (7.8-NE) |
11.9 (2.7-NE) |
Hazard Ratio ( |
|
|
|
DZ vs Z |
0.64 (0.32-1.25) |
|
|
DZ vs chemo |
0.43 (0.20, 0.93) |
|
|
Z vs chemo |
|
0.63 (0.30-1.29) |
|
12-Month Survival Rate ( |
|
|
|
Events, % (n) |
36.8 (14) |
52.5 (21) |
70.6 (12) |
Progression-Free Survival (PFS)** |
|||
Median, months ( |
11.5 (4.0-26.2) |
6.2 (2.5-12.3) |
9.6 (2.6-16.4) |
Hazard Ratio ( |
|
|
|
DZ vs Z |
0.69 (0.40-1.18) |
|
|
DZ vs chemo |
0.69 (0.35, 1.38) |
|
|
Z vs chemo |
|
1.07 (0.56-2.05) |
|
Events, % (n) |
36.8 (14) |
75.0 (30) |
76.5 (13) |
Confirmed Objective Response Rate** |
|||
% (n)
[ |
44.7 (17) [28.6-61.7] |
35.0 (14) [20.6-51.7] |
35.3 (6) [14.2-61.7] |
CI: confidence interval; NE: not evaluable; NR: not reached. |
|||
*Carboplatin with either paclitaxel or pemetrexed. |
|||
**Assessed per investigator according to RECIST v1.1. |
|||
DZ and Z were generally well tolerated with no new safety concerns at the time of DCO. Treatment-related adverse events (TRAEs) leading to treatment discontinuation were higher for chemotherapy (
Investors may dial into the earnings conference call at +1 (404) 975-4839 (local) or +1 (833) 470-1428 (toll-free), using Access Code: 940081, on Wednesday, Nov. 6, 2024, at 2:00 PM PT / 5:00 PM ET. Participants may also register for the call online using this link: https://www.netroadshow.com/events/login?show=4818aee3&confId=72838. To access the live webcast and accompanying slide presentation, please visit the “Investors & Media” section of the Arcus Biosciences website at www.arcusbio.com. A replay will be available following the live event.
About the ARC-10 Study
ARC-10 was initially initiated and conducted as a randomized Phase 3 trial; the protocol was subsequently amended to evaluate domvanalimab plus zimberelimab versus pembrolizumab (part 2). Part 1 of the ARC-10 study is a multicenter, randomized, open-label study for patients with front-line locally advanced or metastatic squamous or non-squamous NSCLC with PD-L1 TPS ≥
About Domvanalimab
Domvanalimab is the most clinically advanced Fc-silent investigational monoclonal antibody that was 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 activating 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 anti-tumor 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
Domvanalimab and zimberelimab are investigational molecules. Arcus and Gilead have not received approval from any regulatory authority for any commercial use globally, and their safety and efficacy for the treatment of lung cancer have not been established.
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, HIF-2a, CD73, dual A2a/A2b receptor, CD39, and AXL. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com.
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. Nuyten’s and Dr. Johnson’s quotes and statements regarding the efficacy, safety or potential of domvanalimab and/or zimberelimab; the mechanisms of action for any of our investigational products; and current or future combinations involving our investigational products, including the potential benefit or effect of any such combinations. 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 other ongoing or 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; Arcus’s dependence on the collaboration with Gilead for the successful development and commercialization of its optioned molecules, including domvanalimab and zimberelimab; 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
The Arcus name and logo are trademarks of Arcus Biosciences, Inc. All other trademarks belong to their respective owners.
View source version on businesswire.com: https://www.businesswire.com/news/home/20241105383975/en/
Investor Inquiries:
Pia Eaves
VP of Investor Relations & Strategy
(617) 459-2006
peaves@arcusbio.com
Media Inquiries:
Holli Kolkey
VP of Corporate Affairs
(650) 922-1269
hkolkey@arcusbio.com
Source: Arcus Biosciences
FAQ
What were the survival results for domvanalimab plus zimberelimab in the ARC-10 study for RCUS?
What was the progression-free survival for domvanalimab plus zimberelimab in RCUS's ARC-10 study?
What were the safety results for domvanalimab plus zimberelimab in RCUS's lung cancer trial?
