Adagene Announces Investigator Initiated Phase 2 Trial for Neoadjuvant Muzastotug (ADG126) in Colorectal Cancer
Adagene (NASDAQ: ADAG) has announced an investigator initiated Phase 2 neoadjuvant trial of ADG126 for stage II or III colorectal cancer patients. The trial, identified as NCT06846268, will begin enrollment in April 2025 with expected primary completion in mid-2027.
The study will evaluate ADG126 in combination with KEYTRUDA® before surgery, with a primary endpoint measuring Major Pathologic Response (MPR) in up to 20 patients. MPR is defined as ≤10% residual viable tumor in surgical specimens. Secondary endpoints include complete pathological response, disease-free survival, and safety/tolerability.
Led by Dr. Yong Wei Peng from the National University Cancer Institute, Singapore, the trial will also explore pharmacodynamic effects on the tumor microenvironment's immune profile and ADG126's pharmacokinetic profile in tumor tissues.
Adagene (NASDAQ: ADAG) ha annunciato uno studio clinico di Fase 2 neoadiuvante iniziato da un investigatore per pazienti con cancro colorettale di stadio II o III. Lo studio, identificato come NCT06846268, inizierà l'arruolamento ad aprile 2025, con una completamento primario previsto a metà 2027.
Lo studio valuterà ADG126 in combinazione con KEYTRUDA® prima dell'intervento chirurgico, con un obiettivo primario che misura la Risposta Patologica Maggiore (MPR) in un massimo di 20 pazienti. L'MPR è definita come ≤10% di tumore vitale residuo nei campioni chirurgici. Gli obiettivi secondari includono la risposta patologica completa, la sopravvivenza libera da malattia e la sicurezza/tollerabilità.
Guidato dal Dr. Yong Wei Peng dell'Istituto Nazionale per il Cancro dell'Università Nazionale di Singapore, lo studio esplorerà anche gli effetti farmacodinamici sul profilo immunitario del microambiente tumorale e il profilo farmacocinetico di ADG126 nei tessuti tumorali.
Adagene (NASDAQ: ADAG) ha anunciado un ensayo clínico de Fase 2 neoadyuvante iniciado por un investigador para pacientes con cáncer colorrectal en estadio II o III. El ensayo, identificado como NCT06846268, comenzará la inscripción en abril de 2025, con una finalización primaria esperada a mediados de 2027.
El estudio evaluará ADG126 en combinación con KEYTRUDA® antes de la cirugía, con un objetivo primario que mide la Respuesta Patológica Mayor (MPR) en hasta 20 pacientes. La MPR se define como ≤10% de tumor viable residual en las muestras quirúrgicas. Los objetivos secundarios incluyen la respuesta patológica completa, la supervivencia libre de enfermedad y la seguridad/tolerabilidad.
Dirigido por el Dr. Yong Wei Peng del Instituto Nacional de Cáncer de la Universidad Nacional de Singapur, el ensayo también explorará los efectos farmacodinámicos en el perfil inmunológico del microambiente tumoral y el perfil farmacocinético de ADG126 en los tejidos tumorales.
Adagene (NASDAQ: ADAG)는 II기 또는 III기 대장암 환자를 위한 연구자 주도 2상 네오보조 임상 시험을 발표했습니다. NCT06846268로 식별된 이 시험은 2025년 4월에 등록을 시작하며, 2027년 중반에 주요 완료가 예상됩니다.
이 연구는 수술 전 ADG126과 KEYTRUDA®의 병용 요법을 평가하며, 주요 목표는 최대 20명의 환자에서 주요 병리학적 반응(MPR)을 측정하는 것입니다. MPR은 수술 샘플에서 잔여 생존 종양이 ≤10%로 정의됩니다. 2차 목표에는 완전 병리학적 반응, 무병 생존 및 안전성/내약성이 포함됩니다.
싱가포르 국립대학교 암 연구소의 Yong Wei Peng 박사가 이끄는 이 시험은 또한 종양 미세환경의 면역 프로필에 대한 약리역학적 효과와 종양 조직 내 ADG126의 약리학적 프로필을 탐구할 것입니다.
Adagene (NASDAQ: ADAG) a annoncé un essai clinique de Phase 2 néoadjuvant initié par un investigateur pour des patients atteints de cancer colorectal de stade II ou III. L'essai, identifié sous le nom NCT06846268, débutera le recrutement en avril 2025, avec une date de finalisation primaire prévue pour mi-2027.
L'étude évaluera ADG126 en combinaison avec KEYTRUDA® avant la chirurgie, avec un objectif principal mesurant la Réponse Pathologique Majeure (MPR) chez un maximum de 20 patients. La MPR est définie comme ≤10% de tumeur viable résiduelle dans les échantillons chirurgicaux. Les objectifs secondaires incluent la réponse pathologique complète, la survie sans maladie et la sécurité/tolérance.
Dirigé par le Dr. Yong Wei Peng de l'Institut National du Cancer de l'Université Nationale de Singapour, l'essai explorera également les effets pharmacodynamiques sur le profil immunitaire du microenvironnement tumoral et le profil pharmacocinétique d'ADG126 dans les tissus tumoraux.
Adagene (NASDAQ: ADAG) hat eine von einem Prüfer initiierte Phase-2-Studie zu ADG126 für Patienten mit kolorektalem Krebs im Stadium II oder III angekündigt. Die Studie, die als NCT06846268 identifiziert wurde, wird im April 2025 mit der Rekrutierung beginnen, wobei der Abschluss der primären Endpunkte Mitte 2027 erwartet wird.
Die Studie wird ADG126 in Kombination mit KEYTRUDA® vor der Operation bewerten, wobei der primäre Endpunkt die Major Pathologic Response (MPR) bei bis zu 20 Patienten misst. MPR wird definiert als ≤10% verbleibender vitaler Tumor in chirurgischen Proben. Zu den sekundären Endpunkten gehören die vollständige pathologische Reaktion, das krankheitsfreie Überleben und die Sicherheit/Tolerierbarkeit.
Unter der Leitung von Dr. Yong Wei Peng vom National University Cancer Institute in Singapur wird die Studie auch die pharmakodynamischen Effekte auf das Immunprofil der Tumormikroumgebung und das pharmakokinetische Profil von ADG126 in Tumorgeweben untersuchen.
- New Phase 2 trial expansion into earlier-stage cancer treatment
- Potential for long-term clinical benefits in neoadjuvant setting
- Compelling combination efficacy with pembrolizumab in late-stage MSS CRC patients
- Small trial size of only 20 patients
- Extended timeline with completion in mid-2027
Insights
Adagene's announcement of an investigator-initiated Phase 2 trial for muzastotug (ADG126) in colorectal cancer represents a strategic expansion into the neoadjuvant immunotherapy space for a historically treatment-resistant cancer subtype. The trial will evaluate ADG126 combined with pembrolizumab in stage II/III colorectal cancer patients before surgery, with patient enrollment beginning April 2025.
The study targets microsatellite stable (MSS) colorectal cancer - representing approximately 85% of colorectal cancer cases - which has shown minimal response to existing immunotherapies. This positions the trial to address a substantial unmet medical need in a curative-intent setting.
ADG126's SAFEbody technology represents a potentially significant advancement over first-generation CTLA-4 inhibitors like ipilimumab. This proprietary design enables preferential activation in the tumor microenvironment while remaining relatively inactive in healthy tissues, potentially offering improved safety with maintained efficacy. The dual checkpoint blockade approach (targeting both CTLA-4 and PD-1) is mechanistically rational, as it simultaneously addresses T-regulatory cell depletion and reinvigorates exhausted T cells.
The trial's primary endpoint of Major Pathologic Response provides a relatively quick readout of efficacy compared to survival endpoints, though the mid-2027 completion timeline indicates a multi-year evaluation process. This investigator-initiated design suggests external validation of the approach while potentially reducing Adagene's direct trial costs.
If successful, this study could position Adagene to advance into larger company-sponsored trials, potentially creating a new treatment paradigm for early-stage colorectal cancer where current options remain The focus on pharmacodynamics and pharmacokinetics within the tumor microenvironment will provide valuable mechanistic insights regardless of efficacy outcomes.
- Trial to begin enrolling in April; expected primary completion in mid-2027 -
- Primary study endpoint of rate of major pathological response -
SAN DIEGO and SUZHOU, China, Feb. 27, 2025 (GLOBE NEWSWIRE) -- Adagene Inc. (“Adagene”) (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, today 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 ≤
“The foundation for this neoadjuvant study is supported by the compelling combination efficacy and safety profile of ADG126 with pembrolizumab in late-stage MSS CRC patients,” said Peter Luo, Chairman, CEO, and President of R&D at Adagene. “We believe that advancing immunotherapy into the curative neoadjuvant setting holds significant promise. By combining CTLA-4-mediated T regulatory cell depletion with anti-PD-1’s ability to reinvigorate exhausted T cells, this approach restores anti-tumor immunity, offering patients a head start and the potential for long-term clinical benefits.”
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 and Media Contacts
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