Adagene Announces Updated Data from Phase 1b/2 Study of Muzastotug in Combination with KEYTRUDA® (pembrolizumab) in Colorectal Cancer at ASCO Gastrointestinal Cancers Symposium
Adagene (NASDAQ: ADAG) announced updated clinical data for their Phase 1b/2 study of Muzastotug (ADG126) in combination with KEYTRUDA® for colorectal cancer treatment. The study showed promising results with a 33% overall response rate in microsatellite stable colorectal cancer patients, achieving four confirmed partial responses out of twelve patients using a 20 mg/kg loading dose followed by 10 mg/kg Q3W + pembrolizumab.
The treatment demonstrated a favorable safety profile with no Grade 4/5 treatment-related adverse events and no discontinuations to date. Pruritus was the most common side effect, occurring in 25% of patients. The company plans to expand the study to include patients with liver metastases. All responding patients remain on treatment at maintenance doses of either 10 mg/kg Q3W or Q6W in combination with pembrolizumab.
Adagene (NASDAQ: ADAG) ha annunciato dati clinici aggiornati per il loro studio Fase 1b/2 di Muzastotug (ADG126) in combinazione con KEYTRUDA® per il trattamento del cancro colorettale. Lo studio ha mostrato risultati promettenti con un 33% di tasso di risposta globale nei pazienti con cancro colorettale stabile microsatellitare, raggiungendo quattro risposte parziali confermate su dodici pazienti utilizzando una dose di carico di 20 mg/kg seguita da 10 mg/kg ogni 3 settimane + pembrolizumab.
Il trattamento ha dimostrato un profilo di sicurezza favorevole, senza eventi avversi correlati al trattamento di Grado 4/5 e senza interruzioni fino ad oggi. Il prurito è stato l'effetto collaterale più comune, verificandosi nel 25% dei pazienti. L'azienda prevede di espandere lo studio per includere pazienti con metastasi epatiche. Tutti i pazienti rispondenti rimangono in trattamento con dosi di mantenimento di 10 mg/kg ogni 3 settimane o ogni 6 settimane in combinazione con pembrolizumab.
Adagene (NASDAQ: ADAG) anunció datos clínicos actualizados para su estudio de Fase 1b/2 de Muzastotug (ADG126) en combinación con KEYTRUDA® para el tratamiento del cáncer colorrectal. El estudio mostró resultados prometedores con una tasa de respuesta global del 33% en pacientes con cáncer colorrectal estable en microsatélites, logrando cuatro respuestas parciales confirmadas de un total de doce pacientes utilizando una dosis de carga de 20 mg/kg seguida de 10 mg/kg cada 3 semanas + pembrolizumab.
El tratamiento demostró un perfil de seguridad favorable sin eventos adversos relacionados con el tratamiento de Grado 4/5 y sin interrupciones hasta la fecha. El prurito fue el efecto secundario más común, ocurriendo en el 25% de los pacientes. La compañía planea expandir el estudio para incluir pacientes con metástasis hepáticas. Todos los pacientes respondedores continúan recibiendo tratamiento con dosis de mantenimiento de 10 mg/kg cada 3 semanas o cada 6 semanas en combinación con pembrolizumab.
Adagene (NASDAQ: ADAG)는 KEYTRUDA®와 함께 대장암 치료를 위한 Muzastotug(ADG126)의 1b/2상 연구에 대한 업데이트된 임상 데이터를 발표했습니다. 이 연구는 20 mg/kg의 적정 용량을 사용하여 3주마다 10 mg/kg 및 pembrolizumab을 병용한 결과, 미소위성 안정 대장암 환자에서 33%의 전체 반응률을 보이며 12명 중 4명의 확증된 부분 반응을 달성하는 등 유망한 결과를 보여주었습니다.
이 치료는 Grade 4/5의 치료 관련 부작용이 없었고, 현재까지 중단된 사례도 없으므로 안전 프로필이 우수하게 나타났습니다. 가려움증은 환자의 25%에서 발생했던 가장 흔한 부작용이었습니다. 회사는 간 전이 환자를 포함하도록 연구를 확장할 계획입니다. 모든 반응한 환자는 pembrolizumab과 함께 3주마다 또는 6주마다 10 mg/kg의 유지 용량으로 치료를 받고 있습니다.
Adagene (NASDAQ: ADAG) a annoncé des données cliniques mises à jour pour son étude de Phase 1b/2 de Muzastotug (ADG126) en combinaison avec KEYTRUDA® pour le traitement du cancer colorectal. L'étude a montré des résultats prometteurs avec un taux de réponse globale de 33% chez les patients atteints de cancer colorectal stable en microsatellites, atteignant quatre réponses partielles confirmées sur douze patients utilisant une dose de charge de 20 mg/kg suivie de 10 mg/kg toutes les 3 semaines + pembrolizumab.
Le traitement a montré un profil de sécurité favorable, sans événements indésirables liés au traitement de Grade 4/5 et sans interruptions à ce jour. Le prurit a été l'effet secondaire le plus courant, survenant chez 25% des patients. L'entreprise prévoit d'élargir l'étude pour inclure des patients atteints de métastases hépatiques. Tous les patients répondants restent sous traitement à des doses de maintien de 10 mg/kg toutes les 3 semaines ou toutes les 6 semaines en combinaison avec pembrolizumab.
Adagene (NASDAQ: ADAG) hat aktualisierte klinische Daten für ihre Phase 1b/2-Studie zu Muzastotug (ADG126) in Kombination mit KEYTRUDA® zur Behandlung von Darmkrebs bekannt gegeben. Die Studie zeigte vielversprechende Ergebnisse mit einer 33% Gesamtansprechrate bei Patienten mit mikrosatellitärer stabiler Krebserkrankung, wobei vier bestätigte partielle Ansprechen von zwölf Patienten erreicht wurden, die eine Lade-Dosis von 20 mg/kg gefolgt von 10 mg/kg alle drei Wochen + Pembrolizumab erhielten.
Die Behandlung zeigte ein günstiges Sicherheitsprofil, ohne Grad 4/5 behandlungsbedingte Nebenwirkungen und bis heute keine Unterbrechungen. Juckreiz war die häufigste Nebenwirkung und trat bei 25% der Patienten auf. Das Unternehmen plant, die Studie auf Patienten mit Lebermetastasen auszudehnen. Alle ansprechenden Patienten bleiben in Behandlung mit Erhaltungsdosen von entweder 10 mg/kg alle drei Wochen oder alle sechs Wochen in Kombination mit Pembrolizumab.
- 33% overall response rate in microsatellite stable colorectal cancer patients
- Four confirmed partial responses out of twelve patients
- No treatment discontinuations reported
- No Grade 4/5 treatment-related adverse events observed
- All responders remain on treatment
- Higher Grade 2/3 treatment-related adverse events observed in loading dose cohort
- 25% of patients experienced pruritus as side effect
Insights
The latest data from Adagene's Phase 1b/2 trial represents a significant advancement in treating microsatellite stable colorectal cancer (MSS CRC), a notoriously difficult-to-treat cancer subtype that typically shows poor response to immunotherapy. The 33% overall response rate achieved with the new loading dose regimen (20 mg/kg followed by 10 mg/kg Q3W) marks a substantial improvement over the previous 23% ORR.
The trial's innovative loading dose strategy appears to be key in optimizing the therapeutic window. This approach allows for higher initial drug exposure to establish anti-tumor activity, followed by a maintenance dose that balances efficacy with long-term tolerability. The fact that all responders remain on treatment suggests durable responses, a important factor in immunotherapy success.
ADG126's SAFEbody technology demonstrates a differentiated approach by enhancing intra-tumoral accumulation while minimizing systemic exposure. This is particularly relevant for CTLA-4 inhibition, where the therapeutic window has historically been narrow. The absence of Grade 4/5 adverse events and no treatment discontinuations, despite higher G2/G3 events in the loading dose cohort, suggests a manageable safety profile that could potentially enable broader clinical application.
The planned expansion to include patients with liver metastases could significantly broaden the addressable patient population, as liver metastases are common in CRC and typically associated with poor prognosis. The potential for combination with standard of care treatments could further enhance ADG126's clinical utility and market position.
The clinical data for muzastotug represents a potential breakthrough in MSS CRC treatment, where current immunotherapy approaches have shown success. The 33% response rate is particularly noteworthy given that MSS tumors are traditionally considered 'cold' tumors resistant to immunotherapy. The novel epitope binding and enhanced Treg depletion mechanism, achieved without Fc engineering, suggests a fundamental improvement over existing CTLA-4 inhibitors.
The safety profile is especially impressive in the context of CTLA-4 inhibition, where toxicity has historically been a major limiting factor. While the loading dose cohort showed increased G2/G3 events, the ability to manage these through dose modification rather than discontinuation is clinically significant. The 25% incidence of pruritus as the most common TRAE is notably lower than historical data for other CTLA-4 inhibitors.
The masking technology's ability to increase intra-tumoral accumulation while maintaining optimal plasma concentrations represents a sophisticated approach to the classic efficacy-toxicity trade-off in cancer immunotherapy. This could potentially enable more aggressive dosing strategies without compromising safety, a important factor for combination therapies in colorectal cancer treatment.
Muzastotug (ADG126), an Anti-CTLA-4 SAFEbody® in Combination with pembrolizumab showed
Four confirmed partial responses out of twelve patients with 20 mg/kg loading dose followed by 10 mg/kg Q3W + pembrolizumab
No Grade 4/5 treatment related adverse events were observed and no discontinuations occurred to date
SAN DIEGO and SUZHOU, China, Jan. 27, 2025 (GLOBE NEWSWIRE) -- Adagene Inc. (“Adagene”) (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, announced updated clinical data from ADG126 in microsatellite stable colorectal cancer (MSS CRC) at the ASCO Gastrointestinal (GI) Cancers Symposium in San Francisco, CA.
“These data, from the loading dose expansion cohort of our Phase 1b/2 trial, continue to demonstrate ADG126’s potential for patients with colorectal cancer. Seeing four confirmed partial responses out of twelve patients, with no treatment related discontinuations, also highlights the differentiated therapeutic index of ADG126. CTLA-4 is clinically validated with a known correlation between dose, efficacy and toxicity to improve outcomes with PD-1 inhibitors, and now we know that our SAFEbody can deliver benefit to patients in a safe and efficacious way,” said Peter Luo, Chairman, CEO & President of R&D at Adagene.
Dr. Marwan Fakih, Professor of Medical Oncology and Therapeutics Research at City of Hope added, “Masking technology, which leads to increased intra-tumoral accumulation of cleaved ADG126 and maintains an optimal plasma concentration following higher and repeat dosing of ADG126, as well as enhanced Treg depletion through binding to a novel epitope without Fc engineering, position ADG126 to be a best-in-class CTLA-4 inhibitor.”
This Phase 1b/2, open-label, multicenter dose escalation and expansion combination study of 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 MSS CRC with no liver and peritoneum metastases previously demonstrated efficacy at the 10 mg/kg Q3W dose, with overall response rate (ORR) of
No Grade 4/5 safety events were seen with ADG126 to date and pruritus (
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 in tumor microenvironment, while minimizing on-target off-tumor toxicity in healthy tissues.
Adagene’s lead clinical program, ADG126 (muzastotug), is a masked, anti-CTLA-4 SAFEbody that targets a unique epitope of CTLA-4 in regulatory T cells (Tregs) in the tumor microenvironment. ADG126 is currently in phase 1b/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: https://investor.adagene.com.
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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.
Safe Harbor Statement
This press release contains forward-looking statements, including statements regarding certain clinical results of ADG126, the potential implications of clinical data for patients, and Adagene’s advancement of, and anticipated preclinical activities, clinical development, regulatory milestones, and commercialization of its product candidates. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including but not limited to Adagene’s ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may not support further development or regulatory approval; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of Adagene’s drug candidates; Adagene’s ability to achieve commercial success for its drug candidates, if approved; Adagene’s ability to obtain and maintain protection of intellectual property for its technology and drugs; Adagene’s reliance on third parties to conduct drug development, manufacturing and other services; Adagene’s limited operating history and Adagene’s ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; Adagene’s ability to enter into additional collaboration agreements beyond its existing strategic partnerships or collaborations, and the impact of the COVID-19 pandemic on Adagene’s clinical development, commercial and other operations, as well as those risks more fully discussed in the “Risk Factors” section in Adagene’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Adagene, and Adagene undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.
Investor Contact:
Bruce Mackle
LifeSci Advisors
bmackle@lifesciadvisors.com
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