PRODIGE 113 (FFCD 2314) - REWENEC 01 STUDY Randomized Trial of FOLFIRI + Zimberelimab + Domvanalimab vs FOLFIRI With a Hybrid Synthetic Control Arm in Second Line Treatment of Neuroendocrine Carcinoma of Gastro-enteropancreatic or Unknown Origin. Phase II Comparative Randomized Study - Multicentric

Background Neuroendocrine carcinomas (NECs) of gastro-entero-pancreatic (GEP) or unknown (UK) origin are rare and highly aggressive diseases. The recommended first-line (L1) treatment is platinum-etoposide combination therapy, which has a progression-free survival (PFS) of only 4-9 months and a median overall survival (OS) of approximately 12 months. All patients experience relapse, often rapidly after this first line of chemotherapy. The standard second-line (L2) chemotherapies recommended by ESMO, ENETS, and NCCN, FOLFIRI and FOLFOX, have modest efficacy with a PFS of 3 months and a median OS of 6 months. The BEVANEC study (PHRCK 2014, NCT02820857) reported no benefit of FOLFIRI + bevacizumab compared to FOLFIRI in a randomized phase II study that enrolled 150 patients in 26 centers over a period of 5 years in France.
To date, the most promising efficacy data for this highly aggressive cancer come from clinical trials of immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 checkpoint. For example, in France, the non-comparative phase II NIPINEC trial (NCT03591731) randomized patients to receive nivolumab +/- ipilimumab in L2/3 and achieved its primary evaluation criterion (ORR-8 weeks>10%). Other trials in Europe and worldwide have also reported efficacy data in the context of single-arm studies.
Scientific Questions and Unmet Needs:
1. New therapeutic options/perspectives are necessary for patients with GEP/UK NECs given the limited overall survival.
2. Approximately 50% of patients experienced early progression under immunotherapy in the NIPINEC trial and other trials, which may be explained by the absence of chemotherapy combined with immunotherapy and/or the existence of resistance mechanisms.
3. In the GEP/UK NEC indication, the design of these immunotherapy trials has been non-comparative single-arm studies because the realization of randomized comparative trials is considered very difficult for these very rare cancers (incidence <5/million).
Rationale for the REWENEC-01 Trial The DURIGAST PRODIGE 59 study, conducted by the FFCD, demonstrated the feasibility and safety of the FOLFIRI + double immune checkpoint inhibitor (anti-PD-1 and anti-CTLA4) combination, as well as for the combination Folfox-Domvanalimab-Zimberelimab (anti-PD-1 and anti-TIGIT). In a translational study of the immune phenotype in patients with NECs treated with the anti-PD1 pembrolizumab, an increase in TIGIT expression was observed after pembrolizumab treatment and higher TIGIT expression on T cells in the blood of patients with high Ki67 expression in their tumors. These data suggest that TIGIT is a potential complementary therapeutic target to PD-1/PD-L1 checkpoint inhibition in GEP/UK NECs. Domvanalimab has been developed as an anti-TIGIT monoclonal antibody and zimberelimab as an anti-PD-1.
Design and primary objective of the REWNEC-01 Trial The REWENEC-01 trial is a comparative phase II trial that will randomize GEP/UK NEC patients between an experimental arm FOLFIRI+Zimberelimab + Domvanalimab and a control arm FOLFIRI in L2. The FOLFIRI arm will be a "hybrid" synthetic control arm composed of patients from historical/external data from the FOLFIRI arm of BEVANEC and French retrospective studies RBNEC and CEPD, mixed with patients recruited prospectively during the trial and randomized to the control arm. The randomization ratio for patients included prospectively during the trial will be 4:1 (4 patients assigned to FOLFIRI+Zimberelimab + Domvanalimab for 1 patient assigned to FOLFIRI). The randomization algorithm will take into account "external" patients assigned progressively to the control arm to obtain a 1:1 ratio between the trial arms, with balanced distributions of stratification factors between the two arms.
With 77 patients to be included, this strategy will provide statistical power equivalent to that of a trial including 122 patients, sufficient to demonstrate an advantage in overall survival rate at 12 months from 32% to 50%.
The hypotheses related to efficacy criteria are formulated a priori, as recommended by the FDA guidance document on trials with synthetic/external control arms. The proof of concept has been reported at ESMO 2023. The primary judgment criterion will be the overall survival rate at 12 months because it is a strong and significant criterion for translating the clinical benefit of the Chemotherapy + Zimberelimab + Domvanalimab combination. The design with a hybrid synthetic control arm allows for the consideration of a randomized comparative study in a cancer as rare as neuroendocrine carcinoma.

Start Date01 Apr 2026

Sponsor / Collaborator

Hospices Civils de Lyon

[+1]

NCT07134556

/ Not yet recruitingPhase 2

A Phase II Trial Evaluating the Safety and Efficacy of the Combination of Zimberelimab, Domvanalimab and Sacituzumab Govitecan as First-line Therapy for PD-L1 Positive Advanced Triple-negative Breast Cancer

The ADJUNCT is a single-arm, phase II clinical trial to evaluate the safety and efficacy of the combination of zimberelimab, domvanalimab and sacituzumab govitecan as first-line therapy for patients with PD-L1 positive advanced or metastatic triple-negative breast cancer.

Start Date01 Mar 2026

Sponsor / Collaborator

Medica Scientia Innovation Research SL

NCT07283848

/ WithdrawnPhase 2IIT

A Single-Arm, Phase II Study of Perioperative Zimberelimab + Domvanalimab and Neoadjuvant Chemotherapy in Locally Advanced, Resectable, Gastroesophageal Adenocarcinoma

The purpose of the study is to understand whether study drugs domvanalimab and zimberelimab are safe and effective in combination with standard chemotherapy for patients with operable cancer of the esophagus, stomach, or gastroesophageal junction (where the stomach meets the esophagus).
All participants will receive the study treatment. Participants will receive chemotherapy and two immune therapies drugs (domvanalimab and zimberelimab) for up to 4 months before surgery. After surgery and at least a 4 week recovery, participants will receive domvanalimab and zimberelimab for up to 8 months. After completion of the study treatment, participants will be followed for up to 5 years per standard of care.

Start Date01 Feb 2026

Sponsor / Collaborator

The Massachusetts General Hospital

[+2]

100 Clinical Results associated with Domvanalimab

100 Translational Medicine associated with Domvanalimab

100 Patents (Medical) associated with Domvanalimab

Literatures (Medical) associated with Domvanalimab

01 Jan 2026·Nature Reviews Clinical Oncology

Domvanalimab plus zimberelimab shows promise in upper-tract cancers

Article

Author: Sidaway, Peter

01 Dec 2025·NATURE MEDICINE

Domvanalimab and zimberelimab in advanced gastric, gastroesophageal junction or esophageal cancer: a phase 2 trial

Article

Author: Prusty, Subhransu ; DuPage, Amy ; Wainberg, Zev A ; Sison, Edward Allan R ; Rha, Sun Young ; Janjigian, Yelena Y ; Pelster, Meredith ; Nelson, Sandahl ; Thompson, Amy ; Koralek, Daniel O ; Oh, Do-Youn

Dual inhibition of T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and programmed cell death protein 1 (PD-1) may enhance antitumor immunity in advanced gastroesophageal cancers. Here we report the EDGE-Gastric study, an ongoing, multicenter, international, phase 2 study with three cohorts, one in the first-line setting (cohort A) and two in the second-line or greater setting (cohorts B and C). Cohort A comprises four arms: two nonrandomized (A1 and A2) and two randomized (A3 and A4). In arm A1, presented here, dual blockade of TIGIT and PD-1 with domvanalimab (Fc-silent anti-TIGIT) and zimberelimab (anti-PD-1) plus oxaliplatin, leucovorin, fluorouracil (FOLFOX) was evaluated in patients with previously untreated advanced HER2-negative gastric, gastroesophageal junction or esophageal adenocarcinoma. Among 41 treated patients, the confirmed objective response rate was 59% (90% confidence interval (CI) 44.5-71.6%), median progression-free survival was 12.9 months (90% CI 9.8-14.6 months) and median overall survival was 26.7 months (90% CI 18.4 months to not estimable (NE)). In patients with tumor area positivity ≥1% (PD-L1 positive) and tumor area positivity ≥5% (PD-L1 high), respectively, the objective response rate was 62% (90% CI 45.1-77.1%) and 69% (90% CI 45.2-86.8%), median progression-free survival was 13.2 months (90% CI 11.3-15.2 months) and 14.5 months (90% CI 11.3 months-NE), and median overall survival was 26.7 months (90% CI 19.5 months-NE) and not reached (90% CI 17.4 months-NE). Immune-related adverse events were reported in 27% of patients; the safety profile was consistent with that reported for anti-PD-1 plus platinum-based chemotherapy. Dual TIGIT and PD-1 blockade with domvanalimab and zimberelimab plus chemotherapy demonstrated encouraging efficacy, and the regimen is being evaluated in the phase 3 STAR-221 trial. ClinicalTrials.gov identifier: NCT05329766 .

01 May 2024·Clinical lung cancer

STAR-121: A Phase III Randomized Study of Domvanalimab and Zimberelimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Untreated Metastatic Non–Small Cell Lung Cancer With No Actionable Gene Alterations

Article

Author: Rodriguez-Abreu, Delvys ; Johnson, Melissa ; Todd, Trever ; Gray, Jhanelle E ; Chen, Xueying ; Yu, Xinwei ; Mohammad, Saad ; Bosch-Barrera, Joaquim ; Ahn, Myung-Ju ; Kim, Jongseok ; Reck, Martin

INTRODUCTION:

Dual inhibition with a T-cell immunoreceptor with immunoglobulin and ITIM domains plus programmed death (ligand)-1 (PD[L]-1) inhibitors, with or without chemotherapy, is an emerging therapeutic strategy in metastatic non-small cell lung cancer (mNSCLC). The STAR-121 (NCT05502237) phase III, global, randomized, open-label study will investigate first-line domvanalimab (anti-TIGIT) and zimberelimab (anti-PD-1) plus chemotherapy versus pembrolizumab plus chemotherapy in mNSCLC with no actionable gene alterations.

PARTICIPANTS AND METHODS:

Approximately 720 participants (≥18 years old) with untreated mNSCLC and no EGFR and ALK mutations will be randomized into 3 groups (A, B, or C) in a 4:4:1 ratio and stratified by baseline PD-L1 expression (tumor cells <50% vs. ≥50%), histology (squamous vs. nonsquamous), and geographic region (East Asia vs. non-East Asia). Group A will receive domvanalimab 1200 mg plus zimberelimab 360 mg plus platinum-doublet chemotherapy (PT), group B will receive pembrolizumab 200 mg plus PT, and group C will receive zimberelimab 360 mg plus PT, every 3 weeks. Treatment will be administered until disease progression or intolerable toxicity. Dual primary endpoints are progression-free survival (by blinded independent central review [BICR]) and overall survival for group A versus B. Key secondary endpoints comprise overall response rate (by BICR), safety, and quality of life. Exploratory endpoints include efficacy and safety between groups A and C, pharmacokinetics, patient-reported outcomes, and biomarkers.

CONCLUSION:

Enrollment in the STAR-121 study commenced on October 12, 2022, and is currently ongoing with completion planned by September 2024. The study completion is expected by December 2027.

138

News (Medical) associated with Domvanalimab

07 Jan 2026

·investors.arcusbio.com

Arcus Outlines 2026 Plans for Casdatifan, its Potential Best-in-Class HIF-2a Inhibitor, and its Inflammation Programs

Arcus’s highest priority is to execute on its ongoing Phase 3 trial and overall development plan aimed at establishing casdatifan as the standard-of-care and backbone therapy for clear cell renal cell carcinoma (ccRCC), including the initiation of a Phase 3 trial in the first-line (1L) setting At least three data presentations are planned for casdatifan in 2026, including updated data from the four late-line monotherapy cohorts of the Phase 1/1b ARC-20 study, which will be presented at a medical conference in February 2026 Arcus’s first development candidate for inflammatory and autoimmune diseases, an oral MRGPRX2 antagonist for chronic spontaneous urticaria, is expected to enter the clinic in 2026 With approximately $1 billion of cash and investmentsi, Arcus expects to be able to fund its planned operations until at least the second half of 2028 Arcus will present at the 44th Annual J.P. Morgan Healthcare Conference on Wednesday, January 14, 2026 HAYWARD, Calif.--(BUSINESS WIRE)-- Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules for patients with cancer and inflammatory and autoimmune diseases, today outlined its 2026 priorities for casdatifan and its emerging inflammation and immunology (I&I) programs. “As we enter 2026, the highest priorities for Arcus will be the rapid enrollment of PEAK-1, our Phase 3 study evaluating casdatifan in immunotherapy (IO)-experienced ccRCC patients, and the initiation of a 1L Phase 3 study evaluating casdatifan informed by data from multiple ongoing and soon-to-be initiated Phase 1 combination studies,” said Terry Rosen, Ph.D., chief executive officer of Arcus. “This year, we also expect to advance our first small molecule for inflammatory disease into the clinic.” Casdatifan (HIF-2a inhibitor for ccRCC) Upcoming Data Presentations: Arcus expects to have at least three data readouts for casdatifan, its potential best-in-class HIF-2a inhibitor, during 2026: In February 2026, Arcus plans to present updated data from the four cohorts of the Phase 1/1b ARC-20 study evaluating casdatifan monotherapy in late-line ccRCC at a medical conference. These data will include updated progression-free survival (PFS) data for the 100mg once-daily (QD) cohort of casdatifan and for all four monotherapy cohorts combined (n=121), as well as updated biomarker data correlating erythropoietin suppression with clinical outcomes. Mid-year, Arcus expects to present updated data for approximately 45 patients treated in ARC-20 with casdatifan plus cabozantinib in IO-experienced ccRCC; this cohort evaluates the same combination in the same setting as PEAK-1, an ongoing Phase 3 study, which represents Arcus’s “fast-to-market” strategy in ccRCC. In the second half of the year, Arcus expects to present data from multiple ARC-20 cohorts evaluating casdatifan in early-line metastatic settings, including data from the cohort evaluating casdatifan plus the anti-PD-1 antibody, zimberelimab, in 1L ccRCC. This will be the first presentation of data for a tyrosine kinase inhibitor (TKI)-sparing HIF-2a inhibitor-based regimen in the 1L setting. Data from this cohort are expected to show an acceptable safety profile and early efficacy, including a low rate of primary progression, which is essential in this setting. The cohort is designed to de-risk Arcus’s strategy to displace TKIs as an early-line treatment. This will be the first presentation of data for a tyrosine kinase inhibitor (TKI)-sparing HIF-2a inhibitor-based regimen in the 1L setting. Data from this cohort are expected to show an acceptable safety profile and early efficacy, including a low rate of primary progression, which is essential in this setting. The cohort is designed to de-risk Arcus’s strategy to displace TKIs as an early-line treatment. Development Strategy: Arcus’s development plan is designed to establish casdatifan as a foundational standard of care across multiple settings of ccRCC, which represents a potential global market opportunity of $5 billion or more. Arcus’s ongoing Phase 3 study for casdatifan in IO-experienced ccRCC, PEAK-1, is evaluating casdatifan plus cabozantinib, the most widely used TKI in this setting. Similar Phase 3 trials in this setting have completed enrollment in 18 months or less, and Arcus’s goal is to achieve a similar timeline. Arcus’s strategy in 1L ccRCC is focused on TKI-free regimens, which are enabled by the consistently low rate of primary progression observed with casdatifan across all cohorts and settings evaluated to date. This strategy has the potential to bring about a highly desirable paradigm shift with a first-in-class regimen that delays treatment with TKIs and their associated toxicities to later lines of therapy. The following cohorts are designed to efficiently determine the optimal 1L registrational strategy for casdatifan: Casdatifan plus zimberelimab (Arcus’s anti-PD-1 antibody): This combination is currently being evaluated in ARC-20, and this cohort has completed enrollment. Arcus plans to present data from this cohort in the second half of 2026. Casdatifan plus anti-PD-1-containing regimens: Arcus is planning to initiate new cohorts to evaluate two other TKI-free casdatifan plus anti-PD-1-containing regimens in the 1L setting. Casdatifan plus volrustomig (AstraZeneca’s anti-PD-1/CTLA-4 bispecific antibody): This combination is being evaluated in the eVOLVE-RCC02 study (which is being operationalized by AstraZeneca). Data from these cohorts will inform and enable the initiation of a Phase 3 study for a casdatifan-containing, TKI-free regimen in the 1L setting. Arcus is targeting initiation of this study by year-end 2026. Small-Molecule Inflammation & Immunology Programs Arcus’s I&I strategy leverages the company’s demonstrated capabilities in small-molecule drug discovery, focusing on indications currently dominated by blockbuster injectable biologics and on highly validated targets. Arcus’s I&I portfolio currently includes several oral small molecules, including an MRGPRX2 antagonist and inhibitors of TNF, CCR6 and CD40L. The company is also developing an anti-CD89 antibody that has potential in patients with a type of rheumatoid arthritis that is currently difficult to treat. Arcus expects to advance its lead inflammation program, a potential best-in-class oral MRGPRX2 antagonist for atopic dermatitis and chronic spontaneous urticaria, into clinical development in 2026. The molecule was designed to have exquisite potency, enabling substantially lower-dose target coverage relative to the most advanced MRGPRX2 antagonist in clinical development, thereby avoiding potential exposure-limiting toxicities. Arcus also expects to advance an oral small-molecule TNF inhibitor, a potential treatment for rheumatoid arthritis, psoriasis and inflammatory bowel disease (such as ulcerative colitis), into the clinic in late 2026 or early 2027. Quemliclustat (CD73 inhibitor for pancreatic cancer) Arcus's oncology portfolio also includes quemliclustat, a small-molecule CD73 inhibitor, which is being evaluated in PRISM-1, a registrational Phase 3 study in 1L pancreatic cancer that completed enrollment in September 2025. Results from this study are expected in the first half of 2027. Runway Guidance Arcus has approximately $1 billion of cash and investmentsi and expects to be able to fund its planned operations until at least the second half of 2028. This guidance includes a rapid wind down of the Phase 3 STAR-221 and Phase 2 EDGE-GASTRIC studies. In the first quarter of 2026, Arcus and Gilead expect to conduct an analysis of STAR-121, a Phase 3 study evaluating domvanalimab plus zimberelimab and chemotherapy in 1L non-small cell lung cancer. Depending on the outcome of this analysis, Arcus could realize additional cost savings. Presentation at 44th Annual J.P. Morgan Healthcare Conference Arcus will present at the 44th Annual J.P. Morgan Healthcare Conference at 3:00 pm PT on Wednesday, January 14, 2026. A live webcast of the presentation will be available on the “Investors & Media” section of the Arcus Biosciences website at www.arcusbio.com. A replay will be available following the live event. Domvanalimab, zimberelimab and quemliclustat are investigational molecules, and neither Arcus nor Gilead has received approval from any regulatory authority for any use globally, and their safety and efficacy have not been established. Casdatifan is also an investigational molecule, and Arcus has not received approval from any regulatory authority for any use globally, and its safety and efficacy have not been established. About RCC According to the American Cancer Society, kidney cancer is among the top 10 most commonly diagnosed forms of cancer among both men and women in the U.S., and an estimated 80,980 Americans will be diagnosed with kidney cancer in 2025. Clear cell RCC is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 18%. In 2022, approximately 32,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 20,000 patients receiving first-line treatment. About Casdatifan (AB521) Casdatifan is a small-molecule inhibitor of HIF-2a, a master switch that turns on hundreds of genes in response to low oxygen levels. In a majority of people with the most common form of kidney cancer (clear cell renal cell carcinoma), genetic anomalies result in the dysregulation of this master switch and transformation of normal kidney cells into cancerous ones. Casdatifan was designed to provide deep and durable inhibition of the HIF-2a pathway. Early clinical studies have shown high response rates and a low primary progression rate relative to clinical benchmarks, warranting further investigation in late-stage studies. Casdatifan, which is administered in pill form once daily, has a safety profile that allows it to be investigated in combination with other treatments. 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 U.S. and globally as a foundational anti-PD-1 treatment option in multiple ongoing clinical studies in combination with other immunotherapies. Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights for zimberelimab in greater China, has obtained approval for zimberelimab for the treatment of recurrent or metastatic cervical cancer and for relapsed or refractory classical Hodgkin’s lymphoma. Zimberelimab is not approved for any use in the U.S. or other regions outside of China. Gloria conducts its development and commercialization activities independent of Arcus and Gilead. About Arcus Biosciences Arcus Biosciences is a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules for the treatment of cancer and inflammatory and autoimmune diseases. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of its late-stage portfolio of first- and/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 advanced multiple investigational medicines into registrational clinical trials including casdatifan, a HIF-2a inhibitor for clear cell renal cell carcinoma, and quemliclustat, a small-molecule CD73 inhibitor for pancreatic cancer. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com. Forward Looking Statement 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, Arcus’s goals and strategy for its casdatifan and inflammation and immunology programs; the potential for casdatifan to become a standard‑of‑care or “backbone” therapy or to be best‑in‑class; planned, expected or potential timing, occurrence and content of clinical data readouts, presentations and publications (including those from ARC‑20, eVOLVE‑RCC02, PEAK‑1 and PRISM‑1); the design, initiation, enrollment, conduct and timelines of ongoing or planned clinical trials (including the potential initiation of a 1L Phase 3 study by year‑end 2026 and enrollment goals for PEAK‑1); the anticipated clinical profile of Arcus’s product candidates, including safety, tolerability and activity, and expectations regarding TKI‑sparing regimens; the advancement and therapeutic potential of Arcus’s I&I candidates (including MRGPRX2 antagonist and TNF inhibitor) and the timing of their entry into the clinic; the scope and timing of program wind‑downs; market opportunity estimates; collaboration activities and expectations (including with AstraZeneca and Gilead); and Arcus’s cash runway and other financial or operational expectations. 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: the outcomes of anticipated analyses from ongoing Phase 3 studies with domvanalimab, including STAR-121 and PACIFIC-8; delays in the wind-down of STAR-221 and EDGE-Gastric; the unexpected emergence of adverse events or other undesirable side effects in Arcus’s investigational products, including casdatifan; risks associated with preliminary and interim data not being guarantees that future data will be similar; 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; further changes to Arcus’s strategy and operating plans; changes in the competitive landscape for Arcus’s programs; reliance on collaborators and third parties (including AstraZeneca and Gilead) and related dependencies; regulatory feedback that may alter design or timing; and assumptions underlying cash‑runway guidance and program wind‑downs 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. i Based on cash, cash equivalents and marketable securities balance of $841 million as of September 30, 2025, and net proceeds of approximately $270 million from Arcus’s November 2025 financing. 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 3ImmunotherapyDrug ApprovalPhase 2

06 Jan 2026

·www.biospace.com

Gilead Keeps Dealing With $300M OncoNano Drug Delivery Cancer Pact

iStock, Sundry Photography OncoNano’s platform, called ON-BOARD, packages drugs in pH-sensitive micelles that ensure their specific delivery near tumors, while also preventing systemic exposure. Gilead is joining with Texas’ OncoNano Medicine to deliver one of Gilead’s investigational cancer drugs using the biotech’s platform, fulfilling a promise it made late last year to stay active in business development. Details of the deal, announced Tuesday, were sparse, with the companies revealing only that the arrangement will mean a $300 million windfall for OncoNano—a sum that includes the upfront commitment, milestones and additional payments related to an additional target, if Gilead chooses to expand the collaboration. At the heart of the partnership is OncoNano’s proprietary ON-BOARD platform, which uses “ultra pH-sensitive polymeric micelles” to encapsulate drugs and respond to the cellular environments shared by various cancers, according to the company’s website . This approach not only protects the therapeutic payload from being broken down in the body—therefore preventing systemic exposure—but also ensures their specific release into the tumor’s microenvironment. “We believe it can complement Gilead’s oncology expertise to bring effective treatment options to patients,” OncoNano CEO Kartik Krishnan said in a statement. The companies did not disclose which of Gilead’s cancer drugs they will apply ON-BOARD to. Tuesday’s OncoNano partnership comes after Gilead last month finally gave up on its TIGIT therapy domvanalimab, which it had been developing in partnership with Arcus Therapeutics. The partners were studying domvanalimab in the Phase III STAR-221 trial in first-line advanced gastric and esophageal cancers. An interim analysis at the time found no significant improvements in overall survival compared with Bristol Myers Squibb’s Opdivo—and determined that continuing on with the study would be futile. Gilead and Arcus decided to terminate STAR-221 as well as a Phase II trial called EDGE-Gastric. The collaboration with OncoNano also comes a few months after Gilead expressed an eagerness to spend money in business development, especially looking to improve its portfolios in liver disease, immunology and cancer. CFO Andrew Dickinson, speaking on the company’s Q3 earnings call, said Gilead is looking for “late-stage derisked assets” to pick up “every two to three years at a minimum.”

Phase 2Phase 3Clinical Trial FailureClinical Trial Termination

17 Dec 2025

·www.biospace.com

Lilly’s Triple Triumph, Prasad’s COVID Error, J&J’s Surprise Voucher, M&A Targets

Eli Lilly’s retatrutide exceeds expectations in Phase III, capping off a sparkling 2025 for the obesity titan; an internal FDA safety review finds no confirmed pediatric deaths caused by COVID-19 vaccines, and Commissioner Marty Makary says no black box warning will be attached to the shots; and BioSpace looks at six biotechs that could be pharma’s next buy. > Listen on Spotify > Listen on Apple Products > Listen on Amazon Music > Listen on iHeart Eli Lilly is wrapping up 2025 with record-breaking weight loss in a late-stage trial for its triple hormone receptor agonist retatrutide . Results from the Phase III TRIUMPH-4 trial exceeded analyst expectations, leading BMO Capital markets to cleverly dub it “a true TRIUMPH.” Also in the weight loss arena, Zealand Pharma inked a deal with China’s OTR Therapeutics worth up to $2.5 billion to collaborate on next-gen drugs for obesity and other metabolic diseases, and Rhythm Pharmaceuticals awaits a Dec. 20 FDA verdict for Imcivree in hypothalamic obesity. Turning to the FDA, reports broke late last week that the agency was considering slapping a black box label—its strictest warning—on COVID-19 vaccines. Commissioner Marty Makary denied those reports on Monday, stating on Bloomberg TV that the FDA has “no plans” to make such a move. This follows an internal memo from Vinay Prasad leaked over Thanksgiving in which the CBER director claimed that “at least” 10 children have died “because of” COVID-19 vaccines. An internal safety review published last week refuted this conclusion, instead concluding that between zero and seven deaths could be linked to the shots. Pfizer CEO Albert Bourla , for one, is tired of the recent rhetoric from HHS on vaccines and hopes they are “an anomaly” that will be corrected soon. With strong words about the administration’s sentiment on vaccines, Bourla prominsed Pfizer’s continued investment in vaccines despite declining revenue. Pfizer this week lowered its 2026 guidance to $62.5 billion in revenue, missing analyst consensus. Clinical research 5 of 2025’s Defining Clinical Wins In the midst of regulatory and political upheaval, biopharma’s R&D engine kept running, churning out highs and lows in equal parts. Here are some of this year’s most glorious clinical trial victories. December 15, 2025 · 9 min read · Tristan Manalac The FDA has also granted several approvals in the past week, to Amgen , Milestone Pharmaceuticals and AstraZeneca and Daiichi Sankyo . USAntibiotics also snagged a greenlight, for Augmentin XR , the first approval to be given under the agency’s new Commissioner’s National Priority Voucher (CNPV) program. Also this week, Johnson & Johnson scored a CNPV ticket—without even having to apply—for its investigational combo of Tecvayli plus Darzalex for relapsed or refractory multiple myeloma after the FDA was impressed by Phase III data. In ClinicaSpace this week, we highlighted 5 of 2025’s Defining Clinical Wins and The 5 Most Painful Clinical Trial Failures of 2025 . This past week provided a few more on each front. In the winner’s circle, Immunome’s desmoid tumor drug and and Kyverna’s CAR T for stiff person syndrome both aced pivotal trials, while Sanofi’s MS drug tolebrutinib and Gilead and Arcus’ TIGIT therapy domvanalimab each failed Phase III tests. And in BioPharm Executive, we highlight 6 Biotechs That Could Be Big Pharma’s Next M&A Target , and more M&A predictions for 2026.

Phase 3VaccineDrug ApprovalClinical Result

100 Deals associated with Domvanalimab

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
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
Adenocarcinoma of Esophagus	Phase 3	Georgia	Gilead Sciences Shanghai Pharmaceutical Technology Co. Ltd.	21 Nov 2022

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05329766 (EDGE-Gastric, Pubmed \| Nat Med)	Phase 2	Esophageal Carcinoma \| Advanced gastric carcinoma \| Advanced Gastroesophageal Junction Adenocarcinoma First line HER2-negative	41	Domvanalimab+Zimberelimab+FOLFOX	imwphknfxq(kuhdiyfvec) = qjsvfpkfrv rzwvokqarx (zskxubfknr, 44.5 - 71.6) View more	Positive	18 Oct 2025
				Domvanalimab+Zimberelimab+FOLFOX (PD-L1 positive)	imwphknfxq(kuhdiyfvec) = qhllxlngni rzwvokqarx (zskxubfknr, 45.1 - 77.1) View more
NCT05329766 (EDGE-Gastric, ESMO2025)	Phase 2	Advanced Gastric Adenocarcinoma \| Adenocarcinoma of Esophagus \| Advanced Gastroesophageal Junction Adenocarcinoma First line HER-2-negative	41	Domvanalimab (dom) + Zimberelimab (zim) + FOLFOX (PD-L1 Positive (TAP ≥1%))	xbmtmowldw(qvuubxarbg) = gqgcjlnkgq tosuurjydv (ybtmjqkjju, 45 - 77) View more	Positive	17 Oct 2025
				Domvanalimab (dom) + Zimberelimab (zim) + FOLFOX (PD-L1 High (TAP ≥5%))	xbmtmowldw(qvuubxarbg) = ivbiungpik tosuurjydv (ybtmjqkjju, 45 - 87) View more
NCT05329766 (EDGE-Gastric, Company_Website) Manual	Phase 2	Adenocarcinoma of Esophagus \| Locally Advanced Gastroesophageal Junction Adenocarcinoma \| Locally Advanced Unresectable Gastric Adenocarcinoma	41	Domvanalimab + Zimberelimab + FOLFOX	bmwfxmfmxy(adkqdflxlf) = dyushfgxbo yrjyxxmkyy (pzoppnbvno, 45 - 72) View more	Positive	12 Oct 2025
				Domvanalimab + Zimberelimab + FOLFOX (PD‐L1 Positive (TAP ≥ 1%))	bmwfxmfmxy(adkqdflxlf) = qrfkgtwobb yrjyxxmkyy (pzoppnbvno, 45 - 77) View more
NCT06790706 (IMMUNORARE5, ASCO2025)	Phase 2	Anaplastic Thyroid Carcinoma BRAFV600 mutation \| TIGIT expression	24	DOMVANALIMAB + ZIMBERELIMAB combination	zlsgpdpgjd(tytwmrzwbz) = jdbtmgjrbz unemzeurzp (pprxcmgfxx )	Positive	30 May 2025
NCT04736173 (ARC-10, BusinessWire) Manual	Phase 1	PD-L1 positive Non-Small Cell Lung Cancer PD-L1 High Expression	98	Domvanalimab plus Zimberelimab	aikvroigvq(dnkemdrnkh) = neanfubyay hklhyhrcbm (dvbocstgqy, 13.7 - NE) View more	Positive	05 Nov 2024
				Zimberelimab	aikvroigvq(dnkemdrnkh) = rasnvntfse hklhyhrcbm (dvbocstgqy, 7.8 - NE) View more
603 (SITC2024)	Phase 2	Hepatocellular Carcinoma	29	Domvanalimab + Zimberelimab	tefxuqbazj(jozpdmwjqt) = Treatment-related adverse events (TRAE) defined as any adverse event that was at least possibly attributed to domvanalimab plus zimberelimab occurred in 16 patients (55.2%) and SAEs attributed to study treatment occurred in 2 patients (6.9%). TRAEs that were grade 3 or greater occurred in 3 patients (10.3%) wwbodosjhu (wfyqcrtkkr )	Positive	05 Nov 2024
NCT05724563 (2024 SITC)	Phase 2	Hepatocellular Carcinoma Second line \| Third line	29	Domvanalimab+赛帕利单抗	cqwpvnkads(xaumcihdiy) = euubttcqun ljpoudooiv (xlnhzjwewh ) View more	Positive	05 Nov 2024
NCT05329766 (EDGE-Gastric, BusinessWire) Manual	Phase 2	Gastrointestinal Neoplasms First line PD-L1	41	domvanalimab+Zimberelimab+ Chemotherapy	lxtgziknww(oxutmzqsqw) = ntsvrcsyhz zvndofkmrr (njcbapvcpx, 9.8 - 13.8) View more	Positive	01 Jun 2024
				domvanalimab+Zimberelimab+ Chemotherapy (PD-L1-high)	lxtgziknww(oxutmzqsqw) = pumqxvbjvd zvndofkmrr (njcbapvcpx, 11.3 - NE) View more
NCT05329766 (EDGE-Gastric, Corporate Publications) Manual	Phase 2	Adenocarcinoma of Esophagus \| Locally Advanced Unresectable Gastric Adenocarcinoma \| Metastatic Gastroesophageal Junction Adenocarcinoma First line	41	Domvanalimab+zimberelimab+chemotherapy	nfivycplow(xelzzphmmm) = sarixfvamg mjxtgekdxa (sedbkmtvxk, 42 - 74) View more	Positive	06 Nov 2023
				Domvanalimab+zimberelimab+chemotherapy (PD-L1-high* (TAP ≥5%))	nfivycplow(xelzzphmmm) = qzhnrltgwu mjxtgekdxa (sedbkmtvxk, 52 - 96) View more
NCT04262856 (ARC-7, Corporate Publications) Manual	Phase 2	Non-Small Cell Lung Cancer First line	150	zimberelimab	cllxgeetzf(kdrepmbaoe) = wpbjruonhv cnbxlxiddl (hafsbczhaf, 17.9 - 44.6) View more	Positive	03 Jun 2023
				domvanalimab + zimberelimab	cllxgeetzf(kdrepmbaoe) = vdgpzjwtrj cnbxlxiddl (hafsbczhaf, 26.4 - 54.8) View more

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