muzastotug (ADG126) / Adagene - LARVOL DELTA

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Liver Cancer • Oncology • Solid Tumor • PD-L1

Ivonescimab and ADG126, Alone, and in Combination With Leucovorin and Fluorouracil or FOLFIRI Regimen for the Treatment of Microsatellite Stable Advanced/Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: City of Hope Medical Center | Initiation date: Jul 2026 ➔ Dec 2026

Trial initiation date • Colorectal Cancer • Oncology • 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

INCA 33890-101: A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=570 | Recruiting | Sponsor: Incyte Corporation | N=408 ➔ 570 | Trial completion date: Jan 2027 ➔ May 2029 | Trial primary completion date: Jan 2027 ➔ May 2029

Enrollment change • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

GO42216: A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients with Advanced Liver Cancers (Morpheus-Liver) (clinicaltrialsregister.eu) - P1/2 | N=29 | Recruiting | Sponsor: F. Hoffmann-La Roche AG | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • PD-L1

Ph1b evaluation of ADG126 (muzastotug, an anti-CTLA-4 masking antibody) pembrolizumab (Pembro) IO doublet in combination with fruquintinib (Fruq) in advanced and metastatic microsatellite stable colorectal cancer (AACR 2026) - P1/2 | "Background: ADG126 is a masked anti-CTLA-4 IgG1 antibody with a widened therapeutic index (TI), designed for tumor-selective activation via protease-mediated cleavage. The favorable safety profile of ADG126 + Pembro IO doublet allows its safe combination with Fruq, with ADG126 dosage ~10-15 fold higher than some approved ipilimumab combination dosages (e.g., 1 mpk Q6W, IO doublet only) in other indications. Despite the safety profile of Fruq, this triple combo shows manageable safety with no new safety signals identified compared with IO doublet. The triple combo provides options to manage safety by dropping individual components, such as Fruq."

Combination therapy • Metastases • Colorectal Cancer • Oncology • Solid Tumor

Results from the phase 1b/2 Morpheus liver study in patients with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC): Muzastotug (ADG126: masked anti-CTLA-4 Ab) combination arm (AACR 2026) - P1/2 | "Upon activation ADG126 binds a unique CTLA-4 epitope, blocks CTLA-4 signaling, soft-primes effector T cells, and selectively depletes regulatory T cells (Tregs) with ~10-fold greater antibody-dependent cellular cytotoxicity (ADCC) than ipilimumab. Given the role of Treg-mediated immunosuppression in HCC and the established benefit of atezolizumab (Atezo) and bevacizumab (Bev), the triplet regimen ADG126 + Atezo + Bev may further amplify antitumor immunity... The initial 6 patients treated with ADG126 + Atezo + Bev demonstrated enhanced antitumor activity, PFS and OS, and comparable safety profile compared to the control arm. Observations from two patients for which ADG126 + Atezo therapy continued following Bev discontinuation underscores the potential importance of the ADG126 + Atezo doublet, which is an effective regimen on its own and allows flexibility in treatment after toxicity. These findings support further investigation of ADG126-based combinations for..."

Clinical • Metastases • P1/2 data • Hepatocellular Cancer • Oncology • Solid Tumor

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: Dec 2027 ➔ Sep 2027 | Trial primary completion date: Dec 2027 ➔ Jul 2027

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

AACR Poster Presentations:…Abstract CT083 (GlobeNewswire) - "A Phase 1b/2 single arm study (NCT05405595) is evaluating the triple combination of muzastotug, pembrolizumab and fruquintinib in patients with advanced and metastatic microsatellite stable (MSS) colorectal cancer (CRC). As of February 21, 2026, nine patients have been treated with the triple combination - four (4) patients at a dose of 10 mg/kg every 6 weeks (Q6W) of muzastotug and five (5) patients at a dose of 15 mg/kg Q6W of muzastotug. All patients were without liver metastases (NLM). Interim results demonstrated a 25% ORR (1/4) among patients in the 10 mg/kg arm (6.7 months median follow-up), and a 40% ORR (2/5) among patients in the 15 mg/kg arm (5.9 months median follow-up)."

P1/2 data • Colorectal Cancer

AACR Poster Presentations: Abstract CT054 (GlobeNewswire) - "Interim results from patients in the muzastotug arm (18.8 months median duration of follow-up) demonstrated a 66.7% overall response rate (ORR; 4/6) using HCC-specified modified RECIST v1.1 criteria. ORR was 50.0% (3/6) using RECIST v1.1 criteria. The median progression free survival (mPFS) was 8.2 months (same for both RECIST criteria) and the median overall survival (mOS) was not yet reached at the data cut but was greater than 22 months. These results compared favorably to the 40 patients in the active control arm (17.2 months median duration of follow-up) that demonstrated an ORR of 32.5% (13/40) using HCC-specified modified RECIST v1.1 criteria, mPFS of 5.5 months, and mOS of 17.5 months."

P1/2 data • Hepatocellular Cancer

Updated Data from Phase 1b/2 Study of Muzastotug in Combination with KEYTRUDA (pembrolizumab) in Late-line Patients with Microsatellite Stable Colorectal Cancer Demonstrate Improved Durability of Response (GlobeNewswire) - "As of the latest data cut, muzastotug achieved a 31% (8/26) confirmed overall response rate (ORR) in the combined 20 mg/kg dose cohorts, showing a clear improvement over the 13% ORR (5/39) in the combined 10 mg/kg dose cohorts...Median duration of response (mDOR) was not yet reached in the 20 mg/kg cohorts, with responses ongoing beyond 9 months; confirmed mDOR of 6.2 months in the 10 mg/kg cohorts...Median PFS was 6.7 months in the combined 20 mg/kg cohorts, outperforming the 4.8 months observed in the combined 10 mg/kg cohorts...In the 10 mg/kg cohorts (n=41; median follow-up, 23.8 months), median overall survival was 19.8 months, with 48% of patients alive at two years, showing the long-tail survival typical of CTLA-4 immunotherapy."

P1/2 data • Colorectal Cancer

Adagene Announces Clinical Collaboration with Incyte to Evaluate Muzastotug (ADG126) in Combination with Incyte’s TGFßR2xPD-1 Bispecific Antibody (INCA33890) in Patients with Microsatellite Stable Colorectal Cancer (MSS CRC) (GlobeNewswire) - "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....Phase 1 study of INCA33890 and muzastotug expected to begin in 2026 in 3L MSS CRC patients with and without liver metastases."

Commercial • New P1 trial • Colorectal Cancer

2026 OBJECTIVES (GlobeNewswire) - "(i) Data update from the ongoing Phase 1b/2 study of muzastotug in combination with...KEYTRUDA (pembrolizumab) in 3L+ MSS CRC, including 41 patients in the 10 mg/kg cohorts and 26 patients in the 20 mg/kg cohorts; (ii) Complete enrollment of the ongoing randomized Phase 2 dose-optimization study with muzastotug...; (iii) Provide preliminary clinical data...from investigator-initiated Phase 2 trial for neoadjuvant muzastotug + pembrolizumab in colorectal cancer; (iv) Provide initial clinical data from a new cohort of patients in the ongoing Phase 1b/2 study of muzastotug + pembrolizumab in combination with standard of care (fruquintinib) in MSS CRC patients; (v) Share results of the clinical trial collaboration with Roche, which evaluates muzastotug in triplet combination with atezolizumab and bevacizumab in first-line treatment of locally advanced or metastatic hepatocellular carcinoma (HCC; liver cancer)."

Enrollment status • P1/2 data • P2 data • Colorectal Cancer • Hepatocellular Cancer

PIPELINE HIGHLIGHTS: ADG126 (GlobeNewswire) - "Randomized Phase 2 trial enrollment ongoing, with results expected in 1H 2027; registration trial expected to begin once optimal dose regimen has been established."

New trial • P2 data • Trial status • Colorectal Cancer

Title: Results from the phase 1b/2 Morpheus Liver study in patients with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC): Muzastotug (ADG126: masked anti-CTLA-4 Ab) combination arm (GlobeNewswire) - "...Abstract...selected for presentation at AACR 2026....This poster will share results of the clinical trial collaboration with Roche, which evaluates muzastotug in triplet combination with atezolizumab and bevacizumab in first-line treatment of liver cancer."

P1/2 data • Hepatocellular Cancer

Title: Ph1b evaluation of ADG126 (muzastotug, an anti-CTLA-4 masking antibody) pembrolizumab (Pembro) IO doublet in combination with fruquintinib (Fruq) in advanced and metastatic microsatellite stable colorectal cancer (GlobeNewswire) - "...Abstract...selected for presentation at AACR 2026....This poster will provide initial clinical data from a new cohort of patients in the ongoing Phase 1b/2 study of muzastotug + pembrolizumab in combination with standard of care (fruquintinib) in MSS CRC patients."

P1/2 data • Colorectal Cancer

Molecular complete response to the RIN protocol (regorafenib, ipilimumab, and nivolumab) in a patient with advanced recurrent metastatic mismatch repair proficient/microsatellite stable (pMMR/MSS) rectal cancer. (PubMed, Ther Adv Med Oncol) - "Rectal cancer recurrence remains a major therapeutic challenge, particularly in patients unresponsive to conventional regimens. While previous studies have demonstrated limited benefit of immunotherapy in this tumor subtype, the present findings suggest an emerging therapeutic opportunity that warrants prospective evaluation to confirm efficacy, explore the mechanistic basis, and identify biomarkers predictive of durable response beyond the absence of liver metastases. More effective combinatorial regimens like zanzalintinib and atezolizumb (STELLAR-303) trial, as well as newer generation of CTLA-4 inhibitors like botensilimab, vilastobart, and muzastotug are showing more promise for patients with MSS colorectal cancers in particular who do not have liver metastases (NLM)."

IO biomarker • Journal • Mismatch repair • pMMR • Colorectal Adenocarcinoma • Colorectal Cancer • Embryonal Tumor • Immune Modulation • Immunology • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor • CEACAM5 • KRAS

Adagene’s Muzastotug (ADG126) to be Highlighted in Two Presentations at the 2026 American Association for Cancer Research (AACR) Annual Meeting in San Diego, CA (GlobeNewswire)

Clinical data • Colorectal Cancer • Hepatocellular Cancer

A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=542 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • First-in-human • Monotherapy • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • BRAF • MSI

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: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Dec 2026 ➔ Dec 2027

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

Ivonescimab and ADG126, Alone, and in Combination With Leucovorin and Fluorouracil or FOLFIRI Regimen for the Treatment of Microsatellite Stable Advanced/Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P1 trial • Colorectal Cancer • Oncology • Solid Tumor • CD4

2026 Objectives (GlobeNewswire) - "Q1 2026: Data update from the ongoing Phase 1b/2 study of muzastotug + pembrolizumab in 3L+ MSS CRC, including 41 patients in the 10 mg/kg cohorts and 26 patients in the 20 mg/kg cohorts; Complete enrollment of the ongoing randomized Phase 2 dose-optimization study with muzastotug, which is being conducted in alignment with FDA Project Optimus, and designed to allow dose regimen selection for Phase 3; Provide preliminary clinical data, including pathological responses, to inform future development from investigator-initiated Phase 2 trial for neoadjuvant muzastotug + pembrolizumab in colorectal cancer; Provide initial clinical data from a new cohort of patients in the ongoing Phase 1b/2 study of muzastotug + pembrolizumab in combination with standard of care (fruquintinib) in MSS CRC patients."

Enrollment status • P1/2 data • P2 data • Colorectal Cancer

2026 Objectives (GlobeNewswire) - "Share results of the clinical trial collaboration with Roche, which evaluates muzastotug in triplet combination with atezolizumab and bevacizumab in first-line treatment of locally advanced or metastatic hepatocellular carcinoma (HCC; liver cancer); Establish additional collaboration/licensing agreements."

Commercial • P1/2 data • Hepatocellular Cancer • Liver Cancer

Adagene Inc…announced that the U.S. Food and Drug Administration (FDA) has designated muzastotug, in combination with Merck’s (known as MSD outside of the United States and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), as a Fast Track product for adult patients with microsatellite stable metastatic colorectal cancer (MSS mCRC) without current or active liver metastases. (GlobeNewswire) - "The Fast Track Designation is supported by emerging clinical evidence demonstrating encouraging efficacy, deep and durable responses, and a favorable safety profile of muzastotug across a heavily pretreated patient population."

Fast track • Colorectal Cancer

A phase II trial of neoadjuvant ADG126 and pembrolizumab in locally advanced colorectal cancer (CRC) (ESMO Asia 2025) - P2 | "Exploratory endpoints include ctDNA clearance, ADG126 pharmacokinetics/pharmacodynamics, and immune microenvironment analysis. The study opened in Q2 2025, and recruitment is ongoing."

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