Bevacizumab

AstraZeneca said a treatment regimen anchored by its PD-L1 inhibitor Imfinzi (durvalumab) and anti-CTLA-4 antibody Imjudo (tremelimumab) succeeded in the Phase III EMERALD-3 trial in patients with hepatocellular carcinoma (HCC).The study is seen as an important test of whether using every available treatment strategy right from the start can improve outcomes for liver cancer patients, though some key opinion leaders (KOLs) worry such an aggressive approach may be too harsh for routine practice and could leave patients with fewer treatment options later on.EMERALD-3 includes 760 patients with unresectable, locoregional HCC who are eligible for embolisation. Participants received either the STRIDE regimen – consisting of single-dose Imjudo plus regular-interval Infinzi – with transarterial chemoembolisation (TACE); the same immunotherapy backbone plus Eisai's VEGF receptor inhibitor Lenvima (lenvatinib) and TACE; or TACE alone.Eye on OSAstraZeneca said the quadruplet approach achieved significant and clinically meaningful improvement on the primary endpoint of progression-free survival (PFS), compared to TACE alone. Overall survival (OS), a key secondary endpoint, showed a trend in favour of this combination as well, but data are still immature.Although it hasn't yet been formally tested, AstraZeneca said early data from the treatment arm that didn't receive Lenvima revealed "strong trends" toward improved PFS and OS.The trial will continue to follow OS in both investigational arms, though the company is optimistic. Susan Galbraith, head of oncology haematology R&D at AstraZeneca, said EMERALD‑3 builds on the Phase III HIMALAYA results, "where the STRIDE regimen has already demonstrated durable overall survival benefit."HIMALAYA tested the combination of Imfinzi and Imjudo in HCC patients with advanced, unresectable disease. Long-term data presented at the European Society for Medical Oncology (ESMO) conference in 2024 showed that nearly 20% of patients given the combination were alive at five years, roughly double the OS rate with Bayer's Bayer's Nexavar (sorafenib).However, earlier efforts to combine Imfinzi with TACE got a mixed reception in the Phase III EMERALD‑1 study a few years ago, where PFS benefit depended on the inclusion of Roche's Avastin (bevacizumab).Toxicity concernsMeanwhile, AstraZeneca said the safety profile for each combination in EMERALD-3 was consistent with the known profiles of each medicine, adding there were no new safety findings. More details will be shared at a forthcoming medical meeting and shared with global regulatory authorities.KOLs interviewed for a FirstWord report voiced serious concerns about toxicity especially given the aggressive use of agents targeting PD-L1, CTLA-4 and VEGF pathways in a patient population that often has cirrhosis or compromised liver function."It will be interesting to see how patients tolerate this," said one US-based KOL. "I think one of the issues with EMERALD-1 that we saw was that there were a lot of dropouts…I just wonder about the kind of additional toxicities that we might see when we keep adding therapies. That being said, you might get a prolonged response in some of these patients."

Phase 1 study of INCA33890 and muzastotug expected to begin in 2026 in 3L MSS CRC patients with and without liver metastases Study will be sponsored and conducted by Incyte; Adagene to provide clinical supply of muzastotug Collaboration provides additional validation of muzastotug as a potential backbone therapy for next-generation immuno-oncology combinations SAN DIEGO and SUZHOU, China, April 02, 2026 (GLOBE NEWSWIRE) -- Adagene Inc. (“Adagene”) (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, today announced a clinical collaboration with Incyte (Nasdaq:INCY), to evaluate the combination of muzastotug (ADG126) and INCA33890, a TGFβR2 × PD-1 bispecific antibody, in patients with microsatellite stable colorectal cancer (MSS CRC) with or without liver metastases. Muzastotug in combination with Merck’s (known as MSD outside of the United States and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) has demonstrated encouraging overall response rates and durable responses in a Phase 1b/2 trial in 3L MSS CRC patients. As a monotherapy, INCA33890 has demonstrated promising clinical efficacy and safety in immune checkpoint sensitive and insensitive cancers, including MSS CRC with and without liver metastases. Incyte has recently initiated a Phase 3 study ( NCT07284849 ) evaluating bevacizumab and FOLFOX (standard of care chemotherapy) with or without INCA33890 in 700 first-line MSS CRC patients. “This strategic collaboration marks the second instance in which Adagene’s SAFEbody® technology is being paired with a leading PD-1–based bispecific, further reinforcing muzastotug’s potential as a backbone immunotherapy with a wider therapeutic index for next-generation immuno-oncology combinations,” said Peter Luo, Ph.D., CEO and President of R&D at Adagene. “We look forward to the clinical insights this study may provide to support our belief that muzastotug has the potential to both improve overall response rate and extend survival, meaningfully enhancing the clinical benefit for patients.” “This collaboration allows us to explore a novel combination approach for patients with microsatellite stable colorectal cancer, a disease that remains resistant to current immunotherapies,” said Pablo J. Cagnoni, M.D., President, Head of Research & Development at Incyte. “By evaluating INCA33890 in combination with muzastotug, we aim to better understand whether complementary mechanisms may help enhance anti-tumor immune responses particularly for patients with liver metastases, who have an especially poor prognosis and limited treatment options.” Muzastotug, a masked anti-CTLA-4 SAFEbody® with FDA Fast Track designation, is currently being evaluated in multiple ongoing studies, including: A Phase 1b/2 clinical trial in combination with pembrolizumab in MSS CRC patients without liver metastases. A randomized Phase 2 study in MSS CRC patients without liver metastases designed to determine the optimal dose to advance into a Phase 3 registration trial. A Phase 1b/2 dose escalation and expansion study of muzastotug in combination with Sanofi’s SAR445877 (PD-1 x IL-15 fusion protein) in adults with advanced solid tumors. Under terms of the agreement, Incyte will sponsor and conduct the study and Adagene will provide clinical trial supply of muzastotug. The planned dose escalation portion of the study will evaluate safety and tolerability, followed by an efficacy expansion cohort in patients with chemotherapy-refractory MSS CRC patients with and without liver metastases. MSS CRC is well-known to be largely non-responsive to anti-PD-1 / PD-L1 therapy. INCA33890 monotherapy has demonstrated promising initial clinical efficacy and safety in immune checkpoint sensitive/insensitive tumors, including MSS CRC with and without liver metastases. About Adagene Adagene Inc. (Nasdaq: ADAG) is a platform-driven, clinical-stage biotechnology company committed to transforming the discovery and development of novel antibody-based cancer immunotherapies. Adagene combines computational biology and artificial intelligence to design novel antibodies that address globally unmet patient needs. The company has forged strategic collaborations with reputable global partners that leverage its SAFEbody precision masking technology in multiple approaches at the vanguard of science. Powered by its proprietary Dynamic Precision Library (DPL) platform, composed of NEObody™, SAFEbody, and POWERbody™ technologies, Adagene’s highly differentiated pipeline features novel immunotherapy programs. The company’s SAFEbody technology is designed to address safety and tolerability challenges associated with many antibody therapeutics by using precision masking technology to shield the binding domain of the biologic therapy. Through activation in the tumor microenvironment, this allows for tumor-specific targeting of antibodies, while minimizing on-target off-tumor toxicity in healthy tissues. Adagene’s lead clinical program, muzastotug (ADG126), is a masked, anti-CTLA-4 SAFEbody with FDA Fast Track designation that targets a unique epitope of CTLA-4 in regulatory T cells (Tregs) in the tumor microenvironment. Muzastotug is currently in Phase 1b/2 and Phase 2 clinical studies in combination with anti-PD-1 therapy, particularly focused on metastatic microsatellite-stable (MSS) colorectal cancer (CRC). Validated by ongoing clinical research, the SAFEbody platform can be applied to a wide variety of antibody-based therapeutic modalities, including Fc empowered antibodies, antibody-drug conjugates, and bi/multispecific T-cell engagers. For more information, please visit: . Follow Adagene on WeChat , LinkedIn and X. SAFEbody® is a registered trademark in the United States, China, Australia, Japan, Singapore, and the European Union. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Adagene Contacts: Investors: Raymond Tam raymond_tam@adagene.com Corey Davis, Ph.D. LifeSci Advisors 1-212-915-2577 cdavis@lifesciadvisors.com Media: Lindsay Rocco Elixir Health Public Relations 1-862-596-1304 lrocco@elixirhealthpr.com