IMMUNORARE5: A National Platform of 5 Academic Phase II Trials Coordinated by Lyon University Hospital to Assess the Safety and the Efficacy of the IMMUNOtherapy With Domvanalimab + Zimberelimab Combination in Patients With Advanced RARE Cancers

Immune checkpoint inhibitors (ICI) have revolutionized the management of advanced cancers. However, most rare cancers have been excluded from this progress due to the lack of clinical trials involving these diseases. After the standard first-line treatment, there are no other validated treatments for most of them. The management of these patients in ≥ 2nd line treatment relies on historic poorly effective regimens.
This creates an inequity between patients with frequent cancers beneficiating from medical progresses and approvals of innovative drugs, and patients with rare cancers are still treated with old and toxic drugs.
Few available data on case reports and early phase studies indicate a beneficial role of the immunotherapy in rare cancers.
The investigators assume that the combination of Domvanalimab and Zimberelimab is more effective than historical standard treatments in patients with 5 types of advanced rare cancers, after failure of at least one line of standard treatment in the advanced setting:
* Cohort 1: Peritoneal Mesotheliomas (PM)
* Cohort 2: Gestational Trophoblastic Tumors (GTT)
* Cohort 3: B3 Thymomas and Thymic Carcinomas (TET)
* Cohort 4: Refractory Thyroid Carcinomas (ATC)
* Cohort 5: GEP-NET and carcinoid tumors (GEP-NET (Gastroenteropancreatic neuroendocrine tumors)/TCT (Thoracic carcinoid tumor)/UP-NET (Neuroendocrine tumor of unknown primary))
The primary objective is to assess the efficacy of the combination of Domvanalimab and Zimberelimab in terms of progression-free survival rate at 24 weeks (for cohorts 1,3,5), successful hCG (Human Chorionic Gonadotropin) normalisation rate at 24 weeks for cohort 2 and survival rate for cohort 4.
The secondary objectives are to assess the efficacy of the combination of anti-TIGIT (T cell Immunoreceptor with Ig and ITIM domains) and anti-PD-1 (Programmed Death-1) immunotherapies in terms of overall response rate, progression-free survival (cohort 1-3 and 5), resistance-free survival (cohort 2), overall survival (cohorts 1-3 and 5), duration of the response (cohorts 1-3 and 5); and to assess the tolerability of the doublet of immunotherapy in terms of adverse events.
Patients will be treated until disease progression or alternatively 2 years in case of complete response (upon discussion with the coordinator of the study, the coordinator of the cohort and the investigator), unacceptable toxicity, or death. At the end of treatment, patients will be followed up for at least 1 year.
IMMUNORARE5 is composed of five independent open-label national multicenter single-arm phase II trials, sponsored by Lyon University Hospital, led in collaboration with the corresponding French national reference centers, with a centralized coordination by a dedicated team.
Each phase II trial is designed as a two-stage Simon design, with early termination for futility. For each cohort, a null hypothesis (H0) and an alternative hypotheses (H1) regarding the percentages of patients with success has been defined, with 5% one-sided alpha level and 80% power.
The trial will be conducted in 15 French Centers with an inclusion period of 36 months

Start Date01 May 2025

Sponsor / Collaborator

Hospices Civils de Lyon

CTR20244881

/ RecruitingPhase 2

一项在头颈部鳞状细胞癌受试者中评价创新联合治疗的II期平台研究一项在既往未经治疗的复发或转移性头颈部鳞状细胞癌受试者（不考虑PD-L1表达状态）中评价创新联合治疗的II期研究

[Translation] A Phase II platform study evaluating novel combination therapy in subjects with head and neck squamous cell carcinoma A Phase II study evaluating novel combination therapy in subjects with previously untreated recurrent or metastatic head and neck squamous cell carcinoma (regardless of PD-L1 expression status)

本研究是一项开放性、多中心、随机、概念验证、全球II期平台研究，旨在评估多种创新联合疗法对HNSCC患者的疗效和安全性。灵活的临床研究设计允许根据中期数据提前终止临床有效性有限或出现不可接受毒性的试验治疗组的研究，以及当创新联合治疗可用时，将新的试验治疗组引入平台研究，并调整试验治疗组内正在接受研究的患者亚组人群。子研究01的队列1旨在评价创新联合治疗作为r/m HNSCC受试者一线治疗的有效性和安全性。队列1（治疗组A和治疗组B）采用随机化设计，评估domvanalimab和赛帕利单抗联合含铂双药化疗对比赛帕利单抗联合含铂双药化疗的有效性和安全性。子研究01的队列2是一个生物标志物队列，旨在评估创新联合治疗的作用机制以及治疗的有效性和安全性。本研究计划设置队列2，具体由申办方酌情决定是否启用该队列。

[Translation]

This study is an open-label, multicenter, randomized, proof-of-concept, global Phase II platform study designed to evaluate the efficacy and safety of multiple innovative combination therapies in patients with HNSCC. The flexible clinical study design allows for early termination of the study of the trial treatment group with limited clinical efficacy or unacceptable toxicity based on interim data, as well as the introduction of new trial treatment groups into the platform study when innovative combination therapies become available, and the adjustment of the patient subgroup population being studied within the trial treatment group. Cohort 1 of Substudy 01 is designed to evaluate the efficacy and safety of innovative combination therapies as first-line treatment for subjects with r/m HNSCC. Cohort 1 (treatment groups A and B) uses a randomized design to evaluate the efficacy and safety of domvanalimab and sepalizumab combined with platinum-based doublet chemotherapy versus sepalizumab combined with platinum-based doublet chemotherapy. Cohort 2 of Substudy 01 is a biomarker cohort designed to evaluate the mechanism of action of innovative combination therapies and the efficacy and safety of treatment. Cohort 2 is planned for this study, and the sponsor will decide whether to enable this cohort at its discretion.

Start Date19 Feb 2025

Sponsor / Collaborator

Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.

[+1]

NCT06431633

/ RecruitingPhase 3IIT

A Phase III Clinical Trial of Adjuvant Treatment with Sacituzumab and Zimberelimab for Stage IB-IIIA-IIIB(N2) Previously Resected (R0) Non-small Cell Lung Cancer Patients That Did Not Achieve Pathological Complete Response After Neoadjuvant Treatment_ARIAN

Open-label, phase III, randomized, stratified (PDL1- vs PDL1+), 3 arms, multicenter clinical trial.
129 resected patients (43 per arm) with stage from IB to IIIA and IIIB (N2) non-small cell lung cancer that do not achieve pathologic complete response (pCR) after neoadjuvant treatment.
This clinical trial has 3 arms of treatment. ARM 1: Observation 10 months, ARM 2: treatment with immunotherapy (Zimberelimab) for 13 cycles and ARM 3: treatment with Sacituzumab Govitecan and Zimberelimab for 8 cycles and Zimberelimab monotherapy for 5 cycles.
The primary objective is to evaluate the disease-free survival (DFS): defined as the length of time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time.
Patient accrual is expected to be completed within 2 years, treatment is planned to extend during 1 years and the patients will be followed up for 2 years. The study will end once survival follow-up has concluded.

Start Date04 Feb 2025

Sponsor / Collaborator-

100 Clinical Results associated with Zimberelimab

100 Translational Medicine associated with Zimberelimab

100 Patents (Medical) associated with Zimberelimab

Literatures (Medical) associated with Zimberelimab

01 Feb 2025·LEUKEMIA RESEARCH

Long-term follow-up of zimberelimab in relapsed or refractory classic Hodgkin lymphoma: Insights from the phase Ⅱ YH-S001-04 clinical trial

Article

Author: Lin, Ningjing ; Liu, Zhuogang ; Xu, Bing ; Zhao, Xielan ; Wang, Li ; Zang, Aimin ; Jiang, Yongsheng ; Zhang, Ying ; Zhang, Zhihui ; Ke, Xiaoyan ; Zhou, Hui ; Zhang, Huilai ; Yan, Dongmei ; Hu, Chunhong ; Liu, Hui ; Cui, Jie ; Qi, Junyuan ; Zhang, Mingzhi ; Shao, Zonghong ; Shi, Jinsheng ; Kan, Suisui ; Yang, Shenmiao ; Liu, Lihong ; Xiang, Ying ; Bai, Hai

BACKGROUND:

Treating relapsed or refractory classical Hodgkin lymphoma (R/R cHL) remains challenging. This report extends the three-year follow-up period for the phase Ⅱ YH-S001-04 trial, expanding upon the initial 15.8-month analysis.

METHODS:

Zimberelimab 240 mg was administered every two weeks for two years or until disease progression or death. The endpoint was the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS:

The median follow-up was 38.0 months (3.5-42.8 months). The ORR was 91.6 % (95 % CI, 83.8-95.9). Median PFS was 23.6 months, with a longer PFS in responders (28.5 months) compared to non-responders (9.2 months) (P=0.0098). Complete responders had longer mPFS than partial responders (Not reached vs. 28.5 months, P=0.3469). Relapsed patients had improved mPFS compared to refractory cHL (23.6 vs. 10.6 months, P=0.0061). Patients with ＜3 lines of therapy showed longer mPFS compared to ≥3 lines (not reached vs. 23.6 months, P=0.0095). The 3-year OS rate was 94.0 % (95 % CI, 85.9-97.4). No serious adverse events with incidence >5 %.

CONCLUSIONS:

With encouraging data on both PFS and OS, zimberelimab demonstrates ongoing efficacy and safety in treating R/R cHL, supporting zimberelimab as an effective treatment alternative for R/R cHL (NCT03655483).

01 Jan 2025·SAGE Open Medical Case Reports

Advanced anaplastic thyroid carcinoma with positive expression of PD-L1 response to immune checkpoint inhibitors: A case report

Article

Author: Sang, Die ; Yuan, Yang ; Fan, Shanmin ; Su, Yanfang

Anaplastic thyroid carcinoma (ATC) is one rare type of thyroid carcinoma without standard systemic treatment for advanced disease. Recent evidence has demonstrated promising efficacy of immune checkpoint inhibitors, particularly those targeting programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), in a variety of solid tumors. However, there have been no research of immune checkpoint inhibitors plus chemotherapy in ATC. Here, we present the case of a 37-year-old man with metastatic ATC with positive PD-L1 expression, who achieved long-term remission of 34 months after later-line treatment with zimberelimab (a PD-1 inhibitor) and nab-paclitaxel, followed by single-agent zimberelimab maintenance therapy. After three cycles of the combination treatment, the thyroid lesion and the liver metastases shrank dramatically, leading to the best overall response of partial remission. PD-L1 expression may serve as a potential biomarker for tumor response to immune checkpoint inhibitors in ATC. Our review highlights the need for further studies investigating the role of PD-L1 status as biomarker to predict the prognosis of immunotherapy in the treatment of ATC.

01 Sep 2024·JOURNAL OF PHARMACEUTICAL SCIENCES

Translate Pharmacokinetics of PD-1/PD-L1 Monoclonal Antibodies from Cynomolgus Monkey to Human: Comparison of Different Approaches

Article

Author: Wang, Lu ; Chen, Wenjun ; Jiang, Bo ; Lou, Honggang ; Ruan, Zourong

Antibodies blocking programmed death-1 (PD-1) and its natural ligand programmed death-ligand 1 (PD-L1) have been proved to be promising strategies in recent years. Hundreds of PD-1/PD-L1 antibodies are under development worldwide. Prediction of human pharmacokinetics (PK) in the preclinical stage is critical for designing dosing regimens in first-in-human studies. This study aims to predict the PK of PD-1/PD-L1 antibodies in human by scaling of monkey data. A systematic literature search of published articles on the PK of PD-1/PD-L1 antibodies in cynomolgus monkey and in human was conducted. Allometric scaling (AS), the species time-invariant (STIV) method, as well as physiologically based pharmacokinetic (PBPK) modeling were investigated. Six antibodies (avelumab, atezolizumab, nivolumab, pembrolizumab, cemiplimab, and zimberelimab) were included for investigation. The exponents used in this study were 0.85 and 1 for clearance (CL) and distribution volume (V), respectively, both for AS and STIV methods. The generic PBPK model for macromolecules in PK-Sim was used without further modifications. The dissociation constant of the antibody for binding to FcRn (K_D) in endosome space for human was assumed to be two-fold of that for monkey. Predicted human CLs for the majority of drugs were within the observed range, while Vs were not well predicted using the AS method. The STIV method and the generic PBPK model can be employed to translate concentration-time curves of PD-1/PD-L1 antibodies from cynomolgus monkey to human with comparable efficacy. The results of this study provide reference for the early development of PD-1/PD-L1 antibodies.

105

News (Medical) associated with Zimberelimab

25 Feb 2025

·investors.arcusbio.com

Arcus Biosciences Reports Fourth-Quarter and Full-Year 2024 Financial Results and Provides a Pipeline Update

New data from the Phase 1/1b ARC-20 study showed that casdatifan improved upon the rate of primary progression, overall response rate (ORR) and progression-free survival (PFS) relative to published data from studies with HIF-2a inhibitors to date Initiation of the Phase 3 study for PEAK-1 evaluating casdatifan in combination with cabozantinib versus cabozantinib in immuno-oncology (IO)-experienced patients with clear cell renal cell carcinoma (ccRCC) is expected in the first half of 2025; initial data from the cohort of ARC-20 evaluating casdatifan plus cabozantinib are expected to be presented in mid-2025 Arcus completed a $150 million financing and continues to be well positioned to advance its pipeline with $992 million in cash, cash equivalents and marketable securities as of December 31, 2024 (excluding proceeds from the offering) HAYWARD, Calif.--(BUSINESS WIRE)-- Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, today reported financial results for the fourth quarter and full year ended December 31, 2024, and provided a pipeline update on its clinical-stage investigational molecules across multiple common cancers. “Last week, we presented data from nearly 90 ccRCC patients demonstrating casdatifan’s potential best-in-class profile,” said Terry Rosen, Ph.D., chief executive officer of Arcus. “Given the strong efficacy and preferable safety profile relative to standard-of-care VEGFR tyrosine kinase inhibitors, we believe casdatifan can play an important role in the treatment of every patient diagnosed with ccRCC. Arcus now has full developmental and commercial control of casdatifan, and we are pursuing a robust development plan in multiple ccRCC settings, which include our first Phase 3 trial, PEAK-1, expected to initiate next quarter, as well as our clinical collaboration with AstraZeneca. We are extremely well capitalized to execute on these plans, and we continue to evaluate and pursue opportunities to conserve capital and allocate greater resources to maximizing the potential of casdatifan.” Pipeline Highlights: Casdatifan (HIF-2a inhibitor) Casdatifan Updates: New clinical data from three monotherapy expansion cohorts in ARC-20 were presented in a rapid oral session at the 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium in February. At the time of data cut-off (DCO, January 3, 2025), the efficacy-evaluable population included a total of 87 patients with ccRCC who had received at least two prior lines of therapy, including both an anti-PD-1 and a VEGFR tyrosine kinase inhibitor (TKI) therapy. These data support the potential for casdatifan to be a best-in-class HIF-2a inhibitor for the treatment of ccRCC:Despite limited follow-up, two of the cohorts exceeded 30% confirmed ORR (inclusive of one partial response that confirmed after the DCO) Rates of primary progressive disease (progression at or before their first disease assessment) ranged from 14% to 19% Most patients (81-87%) experienced disease control with either a partial response or stable disease Only two confirmed responders out of the 26 across all cohorts had discontinued due to progression, indicating the potential for a long duration of response A 9.7-month median PFS was reached for the 50mg twice-daily casdatifan monotherapy cohort; median PFS was not yet reached for other cohorts No unexpected safety signals were observed at the time of DCO, and casdatifan had an acceptable and manageable safety profile across all doses Despite limited follow-up, two of the cohorts exceeded 30% confirmed ORR (inclusive of one partial response that confirmed after the DCO) Rates of primary progressive disease (progression at or before their first disease assessment) ranged from 14% to 19% Most patients (81-87%) experienced disease control with either a partial response or stable disease Only two confirmed responders out of the 26 across all cohorts had discontinued due to progression, indicating the potential for a long duration of response A 9.7-month median PFS was reached for the 50mg twice-daily casdatifan monotherapy cohort; median PFS was not yet reached for other cohorts No unexpected safety signals were observed at the time of DCO, and casdatifan had an acceptable and manageable safety profile across all doses Planned Data Readouts: Mid-2025: Safety and initial efficacy data for the ARC-20 cohort evaluating casdatifan plus cabozantinib in IO-experienced patients. Fall 2025: More mature data from the cohorts evaluating casdatifan monotherapy in patients who had progressed on both an anti-PD-1 and a TKI therapy. 2026: More mature data from the casdatifan + cabozantinib cohort and initial data from the new ARC-20 cohorts evaluating casdatifan in the first-line (1L) and IO-experienced settings. Upcoming Study and Cohort Initiations: Three new expansion cohorts within ARC-20 will be initiated in the first quarter of 2025:Casdatifan plus zimberelimab in all-comer 1L ccRCC Casdatifan monotherapy in favorable-risk 1L ccRCC Casdatifan monotherapy in the IO-experienced setting for patients with ccRCC who have not received a VEGFR-TKI therapy The Phase 3 PEAK-1 study evaluating casdatifan in combination with cabozantinib versus cabozantinib in IO-experienced ccRCC is expected to initiate in the second quarter of 2025. A Phase 1b study, part of AstraZeneca’s eVOLVE portfolio of trials, evaluating casdatifan in combination with volrustomig, AstraZeneca’s investigational PD-1/CTLA-4 bispecific antibody, in IO-naive patients, is expected to initiate in 2025. AstraZeneca is operationalizing this study. Casdatifan plus zimberelimab in all-comer 1L ccRCC Casdatifan monotherapy in favorable-risk 1L ccRCC Casdatifan monotherapy in the IO-experienced setting for patients with ccRCC who have not received a VEGFR-TKI therapy Domvanalimab (Fc-silent anti-TIGIT antibody) plus Zimberelimab (anti-PD-1 antibody) Overall survival data from the Phase 2 EDGE-Gastric study, evaluating domvanalimab plus zimberelimab and chemotherapy in upper gastrointestinal (GI) adenocarcinomas, are expected to be presented in the fall of 2025. The first Phase 3 data readout for domvanalimab plus zimberelimab will be from the ongoing Phase 3 study STAR-221 evaluating domvanalimab plus zimberelimab and chemotherapy in PD-L1 all-comer 1L metastatic upper GI adenocarcinomas and is expected in 2026. CD73-Adenosine Axis: Quemliclustat (small-molecule CD73 inhibitor) and Etrumadenant (A2a/A2b receptor antagonist) Quemliclustat: In the fourth quarter of 2024, Arcus initiated PRISM-1, a Phase 3 trial of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in pancreatic cancer. In February 2025, Arcus’s partner, Taiho, dosed their first patient in Japan for PRISM-1. Etrumadenant: Arcus plans to meet with the FDA in the first half of 2025 to clarify next steps for ARC-9, evaluating etrumadenant plus zimberelimab, FOLFOX, chemotherapy and bevacizumab (EZFB) versus regorafenib in third-line metastatic colorectal cancer (mCRC). Early Clinical Programs Evaluation of AB801, a potent and highly selective small-molecule AXL inhibitor, in the dose-escalation phase of a Phase 1/1b study in patients is ongoing. Arcus anticipates advancing this molecule into expansion cohorts in non-small cell lung cancer (NSCLC) in the second half of 2025. Financial Results for Fourth Quarter and Full Year 2024: Cash, Cash Equivalents and Marketable Securities were $992 million as of December 31, 2024, compared to $866 million as of December 31, 2023. The increase during the period is primarily due to the receipt of $320 million in cash from Gilead for their January 2024 equity investment, the receipt of the $100 million option continuation payment from Gilead in July 2024 and proceeds from our $50 million term loan, partially offset by the use of cash in research and development activities. Arcus expects its cash and investments, together with the proceeds from the equity financing in February 2025, will provide funding through our initial pivotal read-outs for domvanalimab, quemliclustat and casdatifan including STAR-221, PRISM-1 and PEAK-1. Revenues were $36 million for the fourth quarter 2024, compared to $31 million for the same period in 2023. In the fourth quarter 2024, Arcus recognized $28 million in License and development service revenues related to the advancement of programs under the Gilead collaboration, as well as $8 million in Other collaboration revenue related to Gilead’s ongoing rights to access Arcus’s research and development pipeline in accordance with the Gilead collaboration agreement. Research and Development (R&D) Expenseswere $111 million for the fourth quarter 2024, compared to $93 million for the same period in 2023. The net increase of $18 million was primarily driven by higher costs associated with our early-stage R&D and preclinical program activities, driven by higher enrollment in our studies for casdatifan, higher expense incurred on Gilead-led studies for domvanalimab, as well as increases in compensation cost related to our growing headcount. Non-cash stock-based compensation expense was $9 million for each of the fourth quarter 2024 and 2023. For the fourth quarter 2024 and 2023, Arcus recognized gross reimbursements of $41 million and $42 million, respectively, for shared expenses from its collaborations, primarily the Gilead collaboration. Gross reimbursements were $165 million for the full year 2024, compared to $162 million for 2023. Our partnership reimbursements were flat compared to the prior year despite the increases in gross costs, due to increases in Gilead-led activities and programs fully funded by us. R&D expense by quarter may fluctuate due to the timing of clinical manufacturing and standard-of-care therapeutic purchases with a corresponding impact on reimbursements. General and Administrative (G&A) Expenseswere $28 million for the fourth quarter 2024, compared to $29 million for the same period in 2023. Non-cash stock-based compensation expense was $8 million for the fourth quarter 2024, compared to $9 million for the same period in 2023. Net Losswas $94 million for the fourth quarter 2024, compared to $81 million for the same period in 2023. Arcus Ongoing and Announced Clinical Studies: Trial Name Arms Setting Status NCT No. Kidney Cancer PEAK-1 cas + cabo vs. cabo Post-IO ccRCC Planned Phase 3 TBD AstraZeneca Collaboration (part of eVOLVE portfolio) cas + volru 2L+ IO-Naive ccRCC Planned Phase 1b TBD ARC-20 cas, cas + cabo 2L+ Cancer Patients/ccRCC Ongoing Phase 1/1b NCT05536141 Upper Gastrointestinal Cancers STAR-221 dom + zim + chemo vs. nivo + chemo 1L Gastric, GEJ and EAC Ongoing Registrational Phase 3 NCT05568095 EDGE-Gastric (ARC-21) dom +/- zim +/- chemo 1L/2L Upper GI Malignancies Ongoing Randomized Phase 2 NCT05329766 Lung Cancer STAR-121 dom + zim + chemo vs. pembro + chemo 1L NSCLC (PD-L1 all-comers) Ongoing Registrational Phase 3 NCT05502237 PACIFIC-8 dom + durva vs. durva Unresectable Stage 3 NSCLC Ongoing Registrational Phase 3 NCT05211895 EDGE-Lung dom +/- zim +/- quemli +/- chemo 1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2 NCT05676931 VELOCITY-Lung dom +/- zim +/- sacituzumab govitecan-hziy or other combos 1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2 NCT05633667 Pancreatic Cancer PRISM-1 quemli + gem/nab-pac vs. gem/nab-pac 1L PDAC Ongoing Randomized Phase 3 NCT06608927 ARC-8 quemli + zim + gem/nab-pac vs. quemli + gem/nab-pac 1L PDAC Ongoing Randomized Phase 1/1b NCT04104672 Colorectal Cancer ARC-9 etruma + zim + mFOLFOX vs. SOC 2L/3L/3L+ CRC Ongoing Randomized Phase 2 NCT04660812 Other ARC-25 AB598 Gastric Cancer Ongoing Phase 1 NCT05891171 ARC-27 AB801 NSCLC Ongoing Phase 1 NCT06120075 cabo: cabozantinib; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; CRC: colorectal cancer; dom: domvanalimab; durva: durvalumab; EAC: esophageal adenocarcinoma; etruma: etrumadenant; GEJ: gastroesophageal junction; gem/nab-pac: gemcitabine/nab-paclitaxel; GI: gastrointestinal; nivo: nivolumab; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma; pembro: pembrolizumab; quemli: quemliclustat; SOC: standard of care; zim: zimberelimab 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, A2a/A2b receptors, CD39 and AXL. For more information about Arcus Biosciences’s clinical and preclinical programs, please visit www.arcusbio.com. Domvanalimab, etrumadenant, quemliclustat and zimberelimab are investigational molecules, and neither Gilead nor Arcus has received approval from any regulatory authority for any use globally, and their safety and efficacy have not been established. Casdatifan, AB598 and AB801 are also investigational molecules, and Arcus has not received approval from any regulatory authority for any use globally, and their safety and efficacy have not been established. About the Gilead Collaboration In May 2020, Arcus established a 10-year collaboration with Gilead to strategically advance our portfolio. Under this collaboration, Gilead obtained time-limited exclusive option rights to all of our clinical programs arising during the collaboration term. Arcus and Gilead are co-developing four investigational products, including zimberelimab (Arcus’s anti-PD-1 molecule), domvanalimab (Arcus’s anti-TIGIT antibody), etrumadenant (Arcus’s adenosine receptor antagonist) and quemliclustat (Arcus’s CD73 inhibitor). The collaboration was expanded in November 2021 and May 2023 to include research directed to two targets for oncology and two targets for inflammatory diseases. 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. Rosen’s quote and statements regarding: Arcus’s expectation that its cash and investments are sufficient to provide funding through its initial pivotal readouts for domvanalimab, quemliclustat and casdatifan; the timing of future study milestones, including the expected timing for data readout for STAR-221 and plans to disclose or present study analyses or data, including any analyses or data from ARC-20 or EDGE-Gastric; whether data and results from studies validate our pipeline or support further development of a program; the potency, efficacy or safety of Arcus’s investigational products, including their potential for a best-in-class profile; and the initiation, design of and associated timing for future studies and cohorts, including statements about PEAK-1 and the new cohorts in ARC-20. 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 preliminary and interim data not being guarantees that future data will be similar; the unexpected emergence of adverse events or other undesirable side effects in Arcus’s investigational products; difficulties or delays in initiating or conducting clinical trials due to difficulties or delays in the regulatory process, enrolling subjects or manufacturing or supplying product for such clinical trials; unfavorable global economic, political and trade conditions; Arcus’s dependence on the collaboration with third parties such as Gilead and Taiho for the successful development and commercialization of its optioned molecules; difficulties associated with the management of the collaboration activities 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 U.S. Securities and Exchange Commission. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this press release. Arcus disclaims any obligation or undertaking to update, supplement or revise any forward-looking statements contained in this press release except to the extent required by law. The Arcus name and logo are trademarks of Arcus Biosciences, Inc. All other trademarks belong to their respective owners. ARCUS BIOSCIENCES, INC. Consolidated Statements of Operations (unaudited) (In millions, except per share amounts) Three Months Ended December 31, Years Ended December 31, 2024 2023 2024 2023 Revenues: License and development service revenue $28 $22 $222 $80 Other collaboration revenue 8 9 36 37 Total revenues 36 31 258 117 Operating expenses: Research and development 111 93 448 340 General and administrative 28 29 120 117 Impairment of long-lived assets — — 20 — Total operating expenses 139 122 588 457 Loss from operations (103) (91) (330) (340) Non-operating income (expense): Interest and other income, net 12 11 52 41 Interest expense (2) — (4) (2) Total non-operating income, net 10 11 48 39 Loss before income taxes (93) (80) (282) (301) Income tax expense (1) (1) (1) (6) Net loss $(94) $(81) $(283) $(307) Net loss per share: Basic and diluted $(1.03) $(1.08) $(3.14) $(4.15) Shares used to compute net loss per share: Basic and diluted 91.7 72.6 90.1 74.0 Selected Consolidated Balance Sheet Data (unaudited) (In millions) December 31, 2024 December 31, 2023 Cash, cash equivalents and marketable securities $992 $866 Total assets 1,150 1,095 Total liabilities 665 633 Total stockholders’ equity 485 462 Derived from the audited financial statements included in the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 25, 2025. 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 Maryam Bassiri AD, Corporate Communications (510) 406-8520 mbassiri@arcusbio.com

Phase 3Phase 1Phase 2Clinical ResultFinancial Statement

19 Feb 2025

·www.biospace.com

Gilead Passes on Option for Arcus’ Cancer Drug Despite Strong Early Data

iStock, Sundry Photography The news comes on the heels of promising Phase I/Ib data, which point to the potential of casdatifan as a more effective alternative to Merck’s Welireg in renal cell carcinoma. Gilead will not move forward with Arcus Biosciences’ casdatifan, an investigational HIF-2a blocker that is being tested for kidney cancer. As per the California biotech’s Tuesday press announcement, Gilead’s window to exercise its exclusive option to obtain rights to casdatifan has “expired.” Arcus will retain full control over the asset and its development path forward. Arcus also announced that it will run a $150 million common stock offering—which Gilead will participate in—to help bankroll future studies of casdatifan. Arcus CEO Terry Rosen in a statement said that the biotech is “thrilled” to keep ownership of casdatifan, which he says “represents a transformational change for Arcus” and allows it to “address a significant unmet need for patients with an estimated $5 billion market opportunity.” Investors, however, are not as enthused: Arcus’ shares dipped 16% to $10.96 on Tuesday, a new 52-week low for the company, per SeekingAlpha . Analysts at Mizuho Securities, on the other hand, appeared optimistic about Arcus, writing in a Tuesday note that the stock offering “could allow [Arcus] to advance the casdatifan program independently” and provide freedom to assess the candidate as a monotherapy or as part of combination regimens. Tuesday’s news comes just days after Arcus presented promising Phase I/Ib data for casdatifan at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium. Results, disclosed over the weekend, showed that a 100-mg dose, given once a day, resulted in a 33% confirmed overall response rate (ORR) and a 52% stable disease rate in patients with metastatic clear cell renal cell carcinoma (RCC). Patients treated with this casdatifan dosage did not reach median progression-free survival (PFS) at the time of the readout, though a different dose level—50 mg twice-daily—had a median PFS of 9.7 months. Arcus is taking the 100-mg dose forward. According to Mizuho, these data suggest that casdatifan is “superior” to Merck’s Welireg (belzutifan), which is also a HIF-2a inhibitor that is FDA-approved for advanced RCC. In particular, the analysts zeroed in on casdatifan’s 9.7-month PFS in the 50-mg, once-daily dose arm, which they say compares favorably to Welireg’s 5.6-month PFS, as indicated in its label . Additionally, casdatifan’s 33% ORR is higher than Welireg’s 22%, as per Mizuho. Cross-study comparisons are inconclusive, however, in the absence of direct head-to-head trials. Arcus plans to ramp up investment to “position casdatifan as the HIF-2a inhibitor of choice,” Rosen said in a statement. The biotech will unveil more data for the therapy throughout 2025 and is preparing to launch another study, dubbed PEAK-1, which will test casdatifan with Cabometyx , Exelixis’s VEGF2 inhibitor, in metastatic clear cell RCC patients who had previously undergone immune-oncology treatments.

Clinical ResultASCODrug ApprovalClinical Study

18 Feb 2025

·www.fiercebiotech.com

Gilead loses interest in Arcus\' kidney cancer rival to Merck\'s Welireg

The casadatifan collaboration was only one facet of a far-reaching, 10-year deal Gilead Sciences struck with Arcus in 2020.\n Gilead Sciences has defied analysts’ expectations by passing on its chance to license Arcus Biosciences’ potential rival to Merck & Co.’s kidney cancer drug Welireg.Gilead had the right to opt in to develop and sell Arcus’ experimental hypoxia-inducible factor-2 alpha (HIF-2a) inhibitor, called casdatifan, once Arcus had delivered a qualifying data package. Last October, the biotech unveiled phase 1 data in metastatic clear cell renal cell carcinoma (ccRCC) showing casdatifan achieved a general overall response rate (ORR) of 34% and a confirmed ORR of 25%. The readout led Evercore analysts to predict that Gilead would opt in to the program by early 2025.But, this morning, the company announced that the window for Gilead to take up this option had expired, and the rights to casdatifan would in fact be staying with Arcus.If Arcus CEO Terry Rosen, Ph.D., was disappointed by Gilead’s decision, he certainly wasn’t showing it. The biotech is “thrilled to retain ownership of casdatifan,” Rosen said in a statement, arguing that the drug “has the potential to address a significant unmet need for patients with an estimated $5 billion market opportunity.”The CEO pointed to updated phase 1 data presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium on Saturday as demonstrating “casdatifan’s potential to be the best-in-class HIF-2a inhibitor in what appears to be a two-horse race” with Merck’s Welireg. That readout showed a 33% confirmed response rate for the 100-mg dose that Arcus is looking to take forward. Arcus has been pitching casdatifan as an alternative to Merck’s Welireg, which is also a HIF-2a inhibitor. Welireg won its second FDA approval in relapsed or refractory renal cell carcinoma in December after being initially approved to treat the rare disease von Hippel-Lindau.“Owning the rights to casdatifan represents a transformational change for Arcus, providing us with significant future strategic optionality,” Rosen said. “We anticipate that every patient with ccRCC will receive a HIF-2a inhibitor, and our development plan is designed to position casdatifan as the HIF-2a inhibitor of choice.”To this end, Arcus will launch a phase 3 study comparing a combo of casdatifan and Exelixis\' Cabometyx versus Cabometyx alone in the second quarter. Arcus has also secured a collaboration to evaluate its drug with AstraZeneca’s investigational anti-PD-1/CTLA-4 bispecific antibody volrustomig in a phase 1 trial of patients who have not yet received an anti-PD-1.But the withdrawal of Gilead’s interest in casdatifan means Arcus has had to look elsewhere to fund the program. As a result, the biotech has also announced this morning a $150 million offering of its common stock, which will fund the phase 3 trial as well as “enable Arcus to rapidly advance casdatifan and maintain the momentum for this program that Arcus has independently built to date.”The casadatifan collaboration was only one facet of a far-reaching, 10-year deal that Gilead struck with Arcus in 2020, paying $175 million upfront for rights to the PD-1 checkpoint inhibitor zimberelimab plus options on the rest of Arcus’ pipeline. Gilead took up options on three Arcus programs the following year, handing the biotech another $725 million.There have been some bumps in the road since then, with Gilead and Arcus announcing a year ago that they were stopping a phase 3 lung cancer TIGIT trial. At the same time, Gilead revealed it would leave Arcus to run a late-stage study of the small-molecule CD73 inhibitor quemliclustat on its own.Still, Gilead kept an interest in Arcus\' work, with the Foster City, California-based pharma plugging a further $320 million into its biotech partner at the time. Arcus said last year that it would use the cash, in part, to help fund its phase 3 trial of casdatifan.

$Gilead loses interest in Arcus\' kidney cancer rival to Merck\'s Welireg$

Phase 1Phase 3ASCODrug ApprovalClinical Result

100 Deals associated with Zimberelimab

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KEGG	Wiki	ATC	Drug Bank
D12063	-	-	-

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Approved

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Indication	Country/Location	Organization	Date
PD-L1 positive Uterine Cervical Cancer	China	Guangzhou Gloria Biosciences Co., Ltd.	30 Jun 2023
Hodgkin's Lymphoma	China	Guangzhou Gloria Biosciences Co., Ltd.	25 Aug 2021

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Carcinoma to the Uterine Cervix	Phase 3	China	Guangzhou Gloria Biosciences Co., Ltd.	01 May 2023
Adenocarcinoma of Esophagus	Phase 3	United States	Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.	21 Nov 2022
Adenocarcinoma of Esophagus	Phase 3	Japan	Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.	21 Nov 2022
Adenocarcinoma of Esophagus	Phase 3	Argentina	Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.	21 Nov 2022
Adenocarcinoma of Esophagus	Phase 3	Australia	Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.	21 Nov 2022
Adenocarcinoma of Esophagus	Phase 3	Belgium	Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.	21 Nov 2022
Adenocarcinoma of Esophagus	Phase 3	Brazil	Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.	21 Nov 2022
Adenocarcinoma of Esophagus	Phase 3	Canada	Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.	21 Nov 2022
Adenocarcinoma of Esophagus	Phase 3	Chile	Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.	21 Nov 2022
Adenocarcinoma of Esophagus	Phase 3	France	Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.	21 Nov 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04999761 (ASCO_GI2025) Manual	Phase 1	Metastatic Esophageal Carcinoma First line	43	Zimberelimab + Futibatinib + cisplatin + fluorouracil	qonnlftzrn(udmenrmrza) = DLTs were evaluated in the first three pts, and none were reported. ckktnrrbuf (tmdbauylkj )	Positive	23 Jan 2025
NCT04736173 (ARC-10, BusinessWire) Manual	Phase 1	PD-L1 positive Non-Small Cell Lung Cancer PD-L1 High Expression	98	Domvanalimab plus Zimberelimab	krrswxghkd(mlhiitnfyg) = cmwaxlhmxe bybxtvkyjo (lgahzsksij, 13.7 - NE) View more	Positive	05 Nov 2024
NCT04736173 (ARC-10, BusinessWire) Manual	Phase 1		98	Zimberelimab	krrswxghkd(mlhiitnfyg) = hqkvlbzclq bybxtvkyjo (lgahzsksij, 7.8 - NE) View more	Positive	05 Nov 2024
NCT03972722 (phase II study, Pubmed \| Int J Gynecol Cancer)	Phase 2	Metastatic Carcinoma to the Uterine Cervix programmed death ligand-1-positive	105	Zimberelimab 240 mg	sgekyfjyyc(reqksuqskv) = 19.0% rupzwdvjqv (ouzmgserem ) View more	Positive	01 Dec 2023
NCT04262856 (ARC-7, Corporate Publications) Manual	Phase 2	Non-Small Cell Lung Cancer First line	150	zimberelimab	ltznelbpet(pbdjtkjigb) = lvcqunrwtd mwoivjyssp (pdxbiddmja, 17.9 - 44.6) View more	Positive	03 Jun 2023
NCT04262856 (ARC-7, Corporate Publications) Manual	Phase 2	Non-Small Cell Lung Cancer First line	150	domvanalimab + zimberelimab	ltznelbpet(pbdjtkjigb) = ltjzoybfum mwoivjyssp (pdxbiddmja, 26.4 - 54.8) View more	Positive	03 Jun 2023
NCT04262856 (ARC-7, ASCO2022) Manual	Phase 2	metastatic non-small cell lung cancer First line PD-L1 High Expression	149	zimberelimab	aehftazkdx(mnsbtbqfmm) = ctxycqwaog ixqjziucci (nkelnloyie, 15.0 - 42.8) View more	Positive	20 Dec 2022
NCT04262856 (ARC-7, ASCO2022) Manual	Phase 2		149	domvanalimab+zimberelimab	aehftazkdx(mnsbtbqfmm) = tpyflbarwy ixqjziucci (nkelnloyie, 26.3 - 56.8) View more	Positive	20 Dec 2022
NCT03972722 (SITC2022 \| ESMO_IO2022) Manual	Phase 2	Uterine Cervical Cancer	90	zimberelimab	eflvqgrvoo(alngntsceb) = zcqzuusqmk pklzbptjnl (ikdlzdlpft, 18.85 - 38.22) View more	Positive	08 Dec 2022
NCT03972722 (CSCO2022)	Phase 2	Recurrent Cervical Cancer \| Metastatic Cervical Carcinoma	105	赛帕利单抗(GLS-010)注射液	zvnnaxztas(dcfjobpkzv) = oybkckbhew jpqirizdee (jvnqptkomp ) View more	-	21 Sep 2022
NCT03655483 (Pubmed \| Eur J Cancer Care (Engl) \| Eur J Cancer) Manual	Phase 2	Classical Hodgkin's Lymphoma Third line	85	zimberelimab	anyfyylptp(hbhuolarep) = lvjcmsrhwx momhuxwyoc (zmkygqivqi, 82.3 - 95.9) View more	Positive	27 Aug 2021
NCT03713905 (Pubmed \| Eur J Cancer Care (Engl) \| Eur J Cancer) Manual	Phase 1	HR-positive/HER2-low Solid Tumors \| Lymphoma	289	GLS-010	uqpqrpnexy(gfvdxpnfiy) = anemia, leukopenia, elevated alanine aminotransaminase/asparate aminotransferase (ALT/AST), and elevated bilirubin bdljtodcbe (rpydimjuij ) View more	Positive	01 May 2021
NCT03713905 (CSCO2020)	Phase 1	Lymphoma	39	GLS-010(赛帕利单抗)	mjenxfujxv(midqdjmwvw) = yphrayjjxk qhtqgbkmbt (yxdquzxfih ) View more	-	19 Sep 2020

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