muzastotug (ADG126) / Adagene - LARVOL DELTA

A Phase II Trial of Neoadjuvant ADG126 and Pembrolizumab in Locally Advanced Colorectal Cancer (CRC) (ESMO Asia 2025) - No abstract available

Clinical • Metastases • P2 data • Colorectal Cancer • Oncology • Solid Tumor

ADG126 Exhibits Clinical Meaningful Efficacy in MSS CRC (Targeted Oncology) - "The combination of ADG126 and pembrolizumab (Keytruda) delivered a durable clinical benefit with a meaningful overall response rate (ORR) of 29% in patients with metastatic microsatellite stable colorectal cancer (MSS CRC). Patients demonstrated a median duration of response (DOR) of 8 months, and an interim median overall survival (OS) of 19.4 months after 18 months of follow-up, according to updated results of a phase 1b/2 trial (NCT05405595) presented during the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Asia Congress 2025....Median progression-free survival (PFS) was 4.8 months (95% CI, 2.6-6.7) in cohort A and 4.5 months (95% CI, 1.4–7.1) in cohort D. PFS was not reached for the combined cohorts B and C (95% CI, 2.7–not available [NA])."

P1/2 data • Colorectal Cancer

Adagene Reports Six Months 2025 Financial Results and Provides Corporate Updates (GlobeNewswire) - "...Adagene has now gained alignment with the FDA on Phase 2 and Phase 3 trial design elements for ADG126, and the Company plans to begin enrollment in 2H 2025. In addition, Adagene has initiated evaluation of ADG126 plus pembrolizumab in combination with standard of care in MSS CRC patients..."

New trial • Trial status • Colorectal Cancer

Research and Development (R&D) Expenses (GlobeNewswire) - "R&D expenses were US$12.0 million for the six months ended June 30, 2025, compared to US$14.7 million for the same period in 2024. The decrease of approximately 18% in R&D expenses reflects clinical focus on and prioritization of the company’s masked, anti-CTLA-4 SAFEbody ADG126."

Commercial • Solid Tumor

Adagene’s ADG126 to be Highlighted in Two Presentations at the 2025 Chinese Society of Clinical Oncology (CSCO) Meeting in Jinan, China (GlobeNewswire)

P1/2 data • Colorectal Cancer

Neoadjuvant ADG126 and Pembrolizumab in Locally Advanced Colorectal Cancer (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: National University Hospital, Singapore | Not yet recruiting ➔ Recruiting | Trial completion date: Oct 2027 ➔ Dec 2027 | Trial primary completion date: May 2027 ➔ Dec 2027

Enrollment open • Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor

Adagene Announces Regulatory Update on Clinical Development Plan for Muzastotug in Microsatellite Stable Colorectal Cancer Following Productive Type B (End of Phase 1) Meeting with FDA (GlobeNewswire) - "Adagene Inc...announced outcomes from its Type B meeting with the United States Food and Drug Administration (FDA). Adagene has received written feedback from the FDA on its clinical development plan to evaluate muzastotug (ADG126) in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab: 200 mg, Q3W) in patients with microsatellite stable colorectal cancer (MSS CRC)....Alignment gained on Phase 2 inclusion/exclusion criteria, primary and secondary endpoints, and study design, including sample size and dosing regimen; Company expects to begin enrolling patients in Phase 2 in 2H 2025."

FDA event • Trial status • Colorectal Cancer

Adagene announces up to $25 million strategic investment from Sanofi (GlobeNewswire) - "Adagene Inc...announced strategic investment and option exercise by Sanofi (Euronext: SAN FP)...Sanofi has agreed to make strategic investment of up to US$25 million in Adagene. The Company plans to use the proceeds to fund its research and development activities, including clinical development of muzastotug (ADG126), an anti-CTLA-4 SAFEbody, through a randomized phase 2 trial in microsatellite stable colorectal cancer (MSS CRC)....To further explore the clinical potential of muzastotug, Adagene will supply Sanofi with muzastotug to evaluate the safety, efficacy, pharmacokinetics and biomarker data in combination with other anticancer therapies in over 100 patients in a phase 1/2 clinical trial in advanced solid tumors. Adagene continues to own worldwide commercial rights to muzastotug."

Financing • Colorectal Cancer

KEYNOTE-C98: ADG126 in Combination With Pembrolizumab in Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=152 | Recruiting | Sponsor: Adagene Inc | Trial completion date: Sep 2025 ➔ Apr 2027 | Trial primary completion date: Mar 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date • Colorectal Cancer • Non Small Cell Lung Cancer • Solid Tumor

Safety and efficacy of ADG126 (an anti-CTLA-4 masking antibody) in combination with pembrolizumab: Updated results of phase 1b/2 study in advanced MSS CRC. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05405595 Background: ADG126 is an anti-CTLA-4 IgG1 masked antibody that is preferentially activated in the tumor upon cleavage of masking peptides in the tumor microenvironment... Dose-dependent ORR has been observed for ADG126/Pembro IO doublet across multiple dose levels/regimens of ADG126 (10 mg/kg Q6W to 20 mg/kg LD) that is associated with well-tolerated to acceptable safety profile, which is enabled by a relatively large therapeutic window. The overall performance of ADG126/Pembro IO doublet warrants further clinical development including combination with SOCs targeting earlier lines/broader populations, such as MSS CRC with liver metastasis. Key efficacy results from MSS CRC patients.120 mg/kg LD: ADG126 20 mg/kg x1 cycle followed by 10 mg/kg Q3W."

Clinical • Combination therapy • Metastases • P1/2 data • Colorectal Cancer

Adagene Announces Updated Data from Phase 1b/2 Study of Muzastotug (ADG126) in Combination with KEYTRUDA (pembrolizumab) in Colorectal Cancer at the American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - P1b/2 | N=131 | NCT05405595 | Sponsor: Adagene Inc | "As of April 22, 2025, a total of 67 MSS CRC patients with no liver metastases including those with peritoneal involvement were treated....In the dose expansion phase of the study, patients in the 10 mg/kg Q3W cohort demonstrated an ORR of 17% and patients in the 20 mg/kg cohorts demonstrated a confirmed ORR of 29%. Median duration of response (DoR) in the 10 mg/kg cohorts was 6.2 months, while the median DoR was not yet reached in the 20 mg/kg cohorts and all the responses are ongoing. Median overall survival (OS) for the 10 mg/kg cohorts was 19.4 months, comparing favorably with current standard of care treatments and historical benchmarks. Median OS for the 20 mg/kg cohorts has not yet been reached. Both 20 mg/kg cohorts achieved equivalent ORRs at 29%, while adverse events were less severe and seen less frequently with Q6W dosing compared to a 20mg/kg loading dose followed by 10mg/kg Q3W."

P1/2 data • Colorectal Cancer

Adagene Announces Upcoming Poster Presentation on Masked Anti-CTLA-4 SAFEbody ADG126 (Muzastotug) at American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "Adagene...announced a poster presentation at ASCO 2025....Abstract Title: Safety and Efficacy of ADG126 (an Anti-CTLA-4 Masking Antibody) in Combination with Pembrolizumab: Updated Results of Phase 1b/2 Study in Advanced MSS CRC; Date: Saturday, May 31, 2025;...Abstract Number: 3579."

P1/2 data • Colorectal Cancer

Adagene Reports Full Year 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "2025 MILESTONES: Provide longer-term time-to-event data from the existing Ph 1b/2 study of ADG126 + pembrolizumab in 3L+ MSS CRC; Update 20 mg/kg loading dose cohort for durability of response (DOR and other time-to-event endpoints); Conduct EOP1 meeting with FDA by Q3 to obtain their endorsement on the proposed dose regimens, trial design and patient population; Initiate evaluation of ADG126 + pembrolizumab in combination with standard of care in MSS CRC patients including those with liver metastases, beginning Q2; Provide initial clinical data from investigator initiated Phase 2 trial for neoadjuvant ADG126 in colorectal cancer."

FDA event • P1/2 data • P2 data • Trial status • Colorectal Cancer • Oncology

Adagene to Present at 11th Annual Immuno-Oncology 360⁰ Summit (GlobeNewswire) - "Adagene Inc...today announced its presentation at the 11th Annual Immuno-Oncology 360⁰ Summit in Boston on March 26, 2025."

Preclinical • Colorectal Cancer

Neoadjuvant ADG126 and Pembrolizumab in Locally Advanced Colorectal Cancer (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: National University Hospital, Singapore

New P2 trial • Colorectal Cancer • Oncology • Solid Tumor

Adagene Announces Investigator Initiated Phase 2 Trial for Neoadjuvant Muzastotug (ADG126) in Colorectal Cancer (GlobeNewswire) - "Adagene Inc...announced an investigator initiated (IIT) Phase 2 neoadjuvant trial of ADG126 for patients with stage II or stage III colorectal cancer....The new study (NCT06846268), led by primary investigator Dr. Yong Wei Peng, Senior Consultant at the Department of Haematology-Oncology, National University Cancer Institute, Singapore, is expected to begin patient enrollment in April 2025. Patients will receive high doses of ADG126 in combination with KEYTRUDA prior to surgery. The trial’s primary endpoint is the rate of Major Pathologic Response (MPR), defined as ≤10% residual viable tumor in the surgical specimen, and will be evaluated in up to 20 patients. Secondary endpoints include complete pathological response, disease-free survival, and safety/tolerability."

Trial status • Colorectal Cancer

Clinical Studies Conducted at Florida Cancer Specialists & Research Institute Expanding Treatment Options and Improving Outcomes for Patients with Gastrointestinal and Genitourinary Cancers (PRNewswire) - "Clinical research conducted at Florida Cancer Specialists & Research Institute, LLC (FCS) is expanding treatment options and contributing to improved outcomes for patients diagnosed with gastrointestinal and genitourinary cancers. FCS research study results are featured at two global gatherings sponsored by the American Society of Clinical Oncology (ASCO)....At the ASCO 2025 Genitourinary Cancers Symposium, Cesar Augusto Perez, MD, as first author, will present results of a Phase I dose-escalation study of the next-generation nectin-4 targeting antibody–drug conjugate CRB-701 (SYS6002) in US and UK patients with urothelial cancer and other solid tumors."

Clinical data • P1 data • Preclinical • Colorectal Cancer • Gastric Cancer • Urothelial Cancer

Update of phase 1b/2 study of muzastotug (ADG126, an anti-CTLA-4 SAFEbody) in combination with pembrolizumab in advanced/metastatic MSS CRC. (ASCO-GI 2025) - P1/2 | "Funded by No funding sources reported Clinical Trial Registration Number: NCT05405595 Background: ADG126 is an anti-CTLA-4 IgG1 masked antibody with cleavable masking peptides that is preferentially activated in the tumor microenvironment, which in turn binds to a unique epitope to block CTLA-4 function, prime T cells and deplete Tregs. Extensive effort on ADG126 dose optimization, aided by PK-informed dosing strategy, suggested that ADG126 10 mg/kg Q6W and Q3W are appropriate dose/regimen for the IO doublet; this is supported by the well-balanced safety and efficacy (ORR, PFS and OS) profile observed in MSS CRC. ADG126 20 mg/kg Q3W appears to have reached safety ceiling for the IO doublet. The totality of the data further verifies that ADG126 possesses potential best-in-class therapeutic index, and provides basis for continued development of the IO doublet in MSS CRC and for additional exploration of the IO doublet in combination with SOCs/other anti-cancer..."

Combination therapy • Metastases • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer

Adagene Announces Updated Data from Phase 1b/2 Study of Muzastotug in Combination with KEYTRUDA (pembrolizumab) in Colorectal Cancer at ASCO Gastrointestinal Cancers Symposium (GlobeNewswire) - P1b/2 | N=131 | NCT05405595 | Sponsor: Adagene Inc | "Newly shared data with the 20 mg/kg loading dose followed by 10 mg/kg Q3W in combination with pembrolizumab achieved an improved ORR of 33%, and all responders remain on treatment at a maintenance dose of 10 mg/kg Q3W or 10 mg/kg Q6W in combination with pembrolizumab....Time to event endpoints will be reported when the data mature in 2025. Due to the enhanced therapeutic index of ADG126 in combination with anti-PD-1, the Company plans to evaluate a broader patient population in the dose expansion cohort, including patients with liver metastases, with standard of care combinations. No Grade 4/5 safety events were seen with ADG126 to date and pruritus (25%) was the most commonly observed treatment-related adverse event (TRAE). Higher G2/G3 TRAEs were observed in the loading dose cohort but were managed through dose modification and infrequent use of infliximab/medical intervention, resulting in no discontinuations to date."

P1/2 data • Colorectal Cancer

Adagene to Announce Updated Data from Phase 1b/2 Study of Muzastotug in Combination with KEYTRUDA (pembrolizumab) in Colorectal Cancer at ASCO Gastrointestinal Cancers Symposium (GlobeNewswire) - "Adagene...will share updated clinical data...on Saturday, January 25, 2025....New data will include initial results from the 20 mg/kg loading dose followed by 10 mg/kg Q3W in combination with pembrolizumab....Company will host a virtual key opinion leader (KOL) event on Saturday, January 25, 2025 at 1:00 PM ET, featuring Aurélien Marabelle, MD, PhD (Université Paris-Saclay), Daneng Li, MD (City of Hope), and Marwan Fakih, MD (City of Hope), who will join company management to discuss the unmet need and current treatment landscape for patients with advanced/metastatic microsatellite-stable (MSS) colorectal cancer (CRC)..."

P1/2 data • Colorectal Cancer

Adagene to Host Virtual KOL Event to Discuss Anti-CTLA-4 SAFEbody ADG126 in Advanced/Metastatic Microsatellite-Stable (MSS) Colorectal Cancer (CRC) on January 25, 2025 (GlobeNewswire) - "Adagene Inc...announced it will host a virtual key opinion leader (KOL) event on Saturday, January 25, 2025 at 1:00 PM ET, featuring Aurélien Marabelle...and Marwan Fakih, MD (City of Hope), who will join company management to discuss the unmet need and current treatment landscape for patients with advanced/metastatic microsatellite-stable (MSS) colorectal cancer (CRC) and why CTLA-4 targeting is essential for achieving durable responses in this cold tumor type....The event will provide a data update on the Phase 1b/2 study of ADG126 (muzastotug) in combination with KEYTRUDA (pembrolizumab) in advanced/metastatic MSS CRC being featured in a poster presentation at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium taking place January 23-25 in San Francisco, California."

Clinical • P1/2 data • Colorectal Cancer

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver) (clinicaltrials.gov) - P1/2 | N=518 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Aug 2026 ➔ Dec 2026 | Trial primary completion date: Aug 2026 ➔ Dec 2026

Metastases • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • PD-L1

Phase 1b/2, multicenter dose escalation and expansion study of muzastotug (ADG126, a masked anti-CTLA-4 SAFEbody®) in combination with pembrolizumab in advanced/metastatic MSS CRC (SITC 2024) - P1/2 | "We previously reported that repeated dosing of Muza as monotherapy had notably fewer Grade 3/4 irAEs than ipilimumab at ~7-fold higher doses (NCT04645069 and Study ADG126-1002), and that Muza/Pembro combination demonstrated promising clinical efficacy in 3L MSS CRC patients free of liver metastasis (NCT05405595). A higher dose Muza (20 mg/kg) allows for a rapid reaching of plasma cleaved drug exposure associated with clinical efficacy and an acceptable safety profile when combined with pembrolizumab. This regimen potentially can offer a best-in-class treatment option for patients with advanced/metastasis MSS CRC.View this table:View inline View popup Download powerpoint Abstract 744 Table 1 Safety and efficacy evaluable patients by dose levels"

Clinical • Combination therapy • Metastases • P1/2 data • Colorectal Cancer • Oncology

Deciphering improved clinical therapeutic index (TI) of Muzastotug (ADG126), a masked anti-CTLA-4 SAFEbody® over its unmasked form (ADG116) as monotherapy or in combination with anti-PD-1 therapy (SITC 2024) - "ADG116, an IgG1 monoclonal antibody targeting a unique epitope of CTLA-4 which is conserved across species, has demonstrated improved TI over ipilimumab via enhanced epitope-dependent ADCC and T cell priming...When combined with toripalimab, muzastotug at 10 mg/kg Q3W showed significantly better safety and similar efficacy versus ADG116 at 3 mg/kg Q6W (highest tolerable regimen)...Modeling predicts a significantly higher and sustained SS tumor-specific engagement of CTLA-4 by muzastotug in patients. The potential best-in-class profile of muzastotug supports further clinical development.1"

Clinical • Combination therapy • IO biomarker • Monotherapy • Oncology • IFNG

Deciphering Improved Clinical Therapeutic Index (TI) of Muzastotug (ADG126), a Masked Anti-CTLA-4 SAFEbody over its Unmasked Form (ADG116) as Monotherapy or in Combination with anti-PD-1 Therapy (toripalimab) (GlobeNewswire) - "New analyses show the seamless translation of preclinical PK analyses to clinical PK data, including: head-to-head comparison of ADG126 to ipilimumab in MC38 mice (colon cancer model), a single dose of ADG126 showed a three-fold increased active (e.g., cleaved) drug exposure in homogenized tumor tissue samples at 10 mg/kg versus a single dose of ipilimumab at 1 mg/kg while maintaining similar plasma active drug exposures; A second analysis in the MC38 mice model showed two consecutive doses of ADG126 at 20 mg/kg increased the tumor cleaved and total PK versus a single dose, demonstrating continuous intratumoral cleavage of intact ADG126 and accumulation within the TME."

Preclinical • Colon Cancer • Gastrointestinal Cancer • Solid Tumor