Adagene Presents Results at ESMO Congress that Show Best-in-Class Therapeutic Potential for Anti-CTLA-4 SAFEbody® ADG126 (Muzastotug) in Combination with KEYTRUDA® (Pembrolizumab) in Advanced/Metastatic Microsatellite-stable (MSS) Colorectal Cancer (CRC)
Adagene Inc. (Nasdaq: ADAG) presented promising results for its anti-CTLA-4 SAFEbody® ADG126 (Muzastotug) in combination with KEYTRUDA® (Pembrolizumab) at the ESMO Congress. The phase 1b/2 trial focused on advanced/metastatic microsatellite-stable (MSS) colorectal cancer (CRC) patients. Key findings include:
1. Doubled confirmed partial responses to four since ASCO GI in MSS CRC patients without liver and peritoneal metastases, with a 24% overall response rate.
2. Median progression-free survival of 8.5 months in patients without liver and peritoneal metastases at ADG126 10 mg/kg Q3W dose.
3. 12-month overall survival rates of 74% for patients without liver metastases and 82% for those without liver and peritoneal metastases at 10 mg/kg dose.
4. Maintained safety profile with only 16% Grade 3 TRAEs in patients treated with ADG126 10 mg/kg Q3W combined with pembrolizumab.
Adagene Inc. (Nasdaq: ADAG) ha presentato risultati promettenti per il suo anti-CTLA-4 SAFEbody® ADG126 (Muzastotug) in combinazione con KEYTRUDA® (Pembrolizumab) durante il Congresso ESMO. La sperimentazione di fase 1b/2 si è concentrata su pazienti con cancro colorettale (CRC) avanzato/metastatico stabile ai microsatelliti (MSS). I principali risultati includono:
1. Le risposte parziali confermate sono raddoppiate da quattro a otto nei pazienti MSS CRC senza metastasi epatiche e peritoneali, con un tasso di risposta globale del 24%.
2. La sopravvivenza libera da progressione mediana è stata di 8,5 mesi in pazienti senza metastasi epatiche e peritoneali alla dose di ADG126 di 10 mg/kg ogni 3 settimane.
3. I tassi di sopravvivenza globale a 12 mesi sono stati del 74% per i pazienti senza metastasi epatiche e dell'82% per quelli senza metastasi epatiche e peritoneali alla dose di 10 mg/kg.
4. Profilo di sicurezza mantenuto con solo il 16% di eventi avversi di grado 3 (TRAEs) nei pazienti trattati con ADG126 10 mg/kg ogni 3 settimane in combinazione con pembrolizumab.
Adagene Inc. (Nasdaq: ADAG) presentó resultados prometedores para su anti-CTLA-4 SAFEbody® ADG126 (Muzastotug) en combinación con KEYTRUDA® (Pembrolizumab) en el Congreso ESMO. El ensayo de fase 1b/2 se centró en pacientes con cáncer colorrectal (CRC) avanzado/metastásico estable a microsatélites (MSS). Los hallazgos clave incluyen:
1. Las respuestas parciales confirmadas se duplicaron de cuatro a ocho en pacientes con MSS CRC sin metástasis hepáticas ni peritoneales, con una tasa de respuesta global del 24%.
2. La supervivencia libre de progresión mediana fue de 8.5 meses en pacientes sin metástasis hepáticas y peritoneales a la dosis de ADG126 de 10 mg/kg cada 3 semanas.
3. Las tasas de supervivencia global a 12 meses fueron del 74% para pacientes sin metástasis hepáticas y del 82% para aquellos sin metástasis hepáticas ni peritoneales a la dosis de 10 mg/kg.
4. Se mantuvo un perfil de seguridad con solo el 16% de eventos adversos de grado 3 (TRAEs) en pacientes tratados con ADG126 10 mg/kg cada 3 semanas en combinación con pembrolizumab.
Adagene Inc. (Nasdaq: ADAG)는 ESMO Congress에서 KEYTRUDA®(Pembrolizumab)와 함께하는 자신의 anti-CTLA-4 SAFEbody® ADG126(Muzastotug)에 대한 유망한 결과를 발표했습니다. 1b/2상 시험은 진행성/전이성 마이크로새틀라이트 안정성(MSS) 대장암(CRC) 환자에 초점을 맞췄습니다. 주요 발견 사항은 다음과 같습니다:
1. 간 및 복막 전이가 없는 MSS CRC 환자에서 ASCO GI 이후 확인된 부분 반응이 4에서 8로 증가하였으며, 전체 반응률은 24%입니다.
2. ADG126 10 mg/kg Q3W 용량에서 간 및 복막 전이가 없는 환자에서 중앙 무진행 생존 기간은 8.5개월입니다.
3. 10 mg/kg 용량에서 간 전이가 없는 환자의 12개월 전체 생존율은 74%, 간 및 복막 전이가 없는 환자는 82%입니다.
4. ADG126 10 mg/kg Q3W와 pembrolizumab을 병용 치료받은 환자에서 16%의 3급 TRAEs로 안전성이 유지되었습니다.
Adagene Inc. (Nasdaq: ADAG) a présenté des résultats prometteurs pour son anti-CTLA-4 SAFEbody® ADG126 (Muzastotug) en combinaison avec KEYTRUDA® (Pembrolizumab) lors du Congrès ESMO. L'essai de phase 1b/2 a porté sur des patients atteints de cancer colorectal (CRC) avancé/métastatique stable par microsatellite (MSS). Les principales conclusions incluent :
1. Les réponses partielles confirmées ont doublé, passant de quatre à huit chez les patients atteints de MSS CRC sans métastases hépatiques et péritonéales, avec un taux de réponse global de 24%.
2. La survie sans progression médiane était de 8,5 mois chez les patients sans métastases hépatiques et péritonéales à une dose de 10 mg/kg d'ADG126 toutes les 3 semaines.
3. Les taux de survie globale à 12 mois étaient de 74% pour les patients sans métastases hépatiques et de 82% pour ceux sans métastases hépatiques ni péritonéales à une dose de 10 mg/kg.
4. Profil de sécurité maintenu avec seulement 16% d'événements indésirables de grade 3 (TRAEs) chez les patients traités avec ADG126 10 mg/kg toutes les 3 semaines en combinaison avec le pembrolizumab.
Adagene Inc. (Nasdaq: ADAG) präsentierte vielversprechende Ergebnisse für sein anti-CTLA-4 SAFEbody® ADG126 (Muzastotug) in Kombination mit KEYTRUDA® (Pembrolizumab) auf dem ESMO-Kongress. Die Phase 1b/2-Studie konzentrierte sich auf Patienten mit fortgeschrittenem/metastasiertem mikrosatellitenstabilem (MSS) kolorektalem Krebs (CRC). Wichtige Ergebnisse umfassen:
1. Die bestätigten partiellen Ansprechraten verdoppelten sich von vier auf acht bei MSS CRC-Patienten ohne Leber- und Peritonealmetastasen, mit einer insgesamt 24%igen Ansprechraten.
2. Die mediane progressionsfreie Überlebenszeit betrug 8,5 Monate bei Patienten ohne Leber- und Peritonealmetastasen bei einer ADG126-Dosis von 10 mg/kg alle 3 Wochen.
3. Die 12-Monats-Gesamtüberlebensraten lagen bei 74% für Patienten ohne Lebermetastasen und 82% für Patienten ohne Leber- und Peritonealmetastasen bei 10 mg/kg.
4. Das Sicherheitsprofil blieb stabil, mit nur 16% Grad 3 TRAEs bei Patienten, die mit ADG126 10 mg/kg alle 3 Wochen in Kombination mit Pembrolizumab behandelt wurden.
- Doubled confirmed partial responses to four in MSS CRC patients without liver and peritoneal metastases
- 24% overall response rate (ORR) with ADG126 10 mg/kg Q3W in combination with pembrolizumab
- Median progression-free survival of 8.5 months observed in patients without liver and peritoneal metastases
- 12-month overall survival rates of 74% for patients without liver metastases and 82% for those without liver and peritoneal metastases
- Low rate of Grade 3 TRAEs (16%) in patients treated with ADG126 10 mg/kg Q3W in combination with pembrolizumab
- No dose-limiting toxicities or Grade 4/5 TRAEs observed at any dose up to 20 mg/kg Q3W
- Overall disease control rate of 88% in patients without liver and peritoneal metastases
- efficacy in patients with liver metastases
- Seven patients developed treatment-related serious adverse events
- 8% discontinuation rate due to adverse events
The data presented at ESMO Congress for ADG126 (muzastotug) in combination with pembrolizumab shows promising results for microsatellite-stable (MSS) colorectal cancer (CRC) patients. The 24% overall response rate and 8.5 months median progression-free survival in patients without liver and peritoneal metastases are significant improvements over current standards. The 12-month overall survival rates of 74-82% for specific patient subgroups are particularly encouraging. The safety profile, with only
The ADG126 SAFEbody technology demonstrates a significant advancement in anti-CTLA-4 therapy. The ability to administer doses up to 20 mg/kg without dose-limiting toxicities is remarkable, potentially allowing for more effective tumor targeting. The lack of Grade 3 colitis and need for infliximab to manage immune-related adverse events suggest a superior safety profile compared to existing CTLA-4 inhibitors. The pharmacokinetic and exposure-response analyses provide important insights for optimizing dosing regimens, aligning with FDA's Project Optimus requirements. The potential for a 20 mg/kg loading dose followed by a 10 mg/kg Q3W maintenance dose could further enhance efficacy while maintaining safety. These findings open up possibilities for combining ADG126 with other therapies and moving into earlier lines of treatment, potentially transforming the landscape of immunotherapy for CRC.
Adagene's ADG126 shows strong potential in the lucrative CRC market, particularly for MSS patients who have treatment options. The improved efficacy and safety profile could lead to significant market penetration if approved. The 24% ORR in a specific patient subset is notably higher than current standards (
- Confirmed partial responses (PRs) doubled to four since ASCO GI in MSS CRC patients without liver and peritoneal metastases for overall response rate (ORR) of
- Median progression-free survival of 8.5 months observed in patients without liver and peritoneal metastases at the ADG126 10 mg/kg Q3W dose -
- At the 10 mg/kg dose level, 12-month overall survival (OS) rates were
- Safety profile maintained, with only
- Combination shows potential with standard of care to address broader patient populations, including MSS CRC patients with liver metastases -
SAN DIEGO and SUZHOU, China, Sept. 16, 2024 (GLOBE NEWSWIRE) -- Adagene Inc. (“Adagene”) (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, today announced new ADG126 clinical data presented at the ESMO Congress, taking place in Barcelona, Spain, September 13-17.
The poster, titled Increased Therapeutic Index of Muzastotug (ADG126), a Masked Anti-CTLA-4 Antibody, in Combination with Pembrolizumab (Pembro) Enables Significant Clinical Benefits and Supports Further Clinical Development in Patients with Metastatic MSS CRC, reports data from an ongoing phase 1b/2 trial of Adagene’s masked anti-CTLA-4 SAFEbody in combination with Merck & Co., Inc., Rahway, NJ, USA's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) (ADG126-P001; NCT05405595).
“I am delighted that the ESMO data show a promising overall response rate, progression-free survival (PFS) and early survival benefit from treatment with the immunotherapy (IO) doublet of ADG126 in combination with pembrolizumab for patients with advanced/metastatic MSS CRC, the largest segment of colorectal cancer with few treatment options,” said Daneng Li, MD, Associate Professor in the Department of Medical Oncology & Therapeutics Research at the City of Hope Comprehensive Cancer Center, and a study investigator. “With a much higher dosing level than available anti-CTLA-4 therapies, these data reinforce the encouraging safety and efficacy profile for ADG126 administered repeatedly in MSS CRC.”
Dr. Li continued, “Given the best-in-class potential for ADG126, this combination with pembrolizumab could address even broader patient populations, such as those with liver metastases, particularly if combined with standard of care to control early disease progression. Further, the safety profile of this immunotherapy doublet enables repeat cycles to achieve and sustain sufficient drug exposure that maximizes potential for a long-term survival benefit.”
ADG126 is a masked anti-CTLA-4 SAFEbody targeting a unique epitope of CTLA-4 on regulatory T cells (Tregs) in tumor tissue which shows potential best-in-class safety and efficacy profiles in combination with pembrolizumab. The unique epitope of ADG126 alone has shown enhanced antibody-dependent cell mediated cytotoxicity without Fc engineering, which is associated with significantly increased toxicity. Further, it has shown minimal immunogenicity and anti-drug antibodies, with no impact on its pharmacokinetic (PK) profile.
Key highlights from the poster (July 30, 2024 data cutoff) include:
- ADG126 in combination with pembrolizumab continued to demonstrate a differentiated safety profile in dose escalation and dose expansion cohorts for heavily pre-treated advanced/metastatic patients with solid tumors (n=66):
- No dose-limiting toxicities (DLT) or Grade 4 or 5 TRAEs were observed at any dose up to 20 mg/kg Q3W, which was evaluated in dose escalation (n=6) to support an ongoing loading dose cohort.
- No Grade 3 colitis was observed at any dose, with limited use of infliximab to manage immune-mediated diarrhea/colitis in no more than
10% of patients. - No significant late-onset toxicities were observed after repeat dosing at the 10 mg/kg dose level. TRAEs by week from treatment start are summarized in the poster.
- Grade 3 TRAEs occurred in only
6% of patients at the 10 mg/kg Q6W dose (1/17) and16% of patients at the 10 mg/kg Q3W dose (6/37). Standard of care treatments are associated with higher rates of toxicities. - Seven patients developed treatment related SAEs; however, the discontinuation rate remains low at
8% (5/66).
- No dose-limiting toxicities (DLT) or Grade 4 or 5 TRAEs were observed at any dose up to 20 mg/kg Q3W, which was evaluated in dose escalation (n=6) to support an ongoing loading dose cohort.
- ADG126 administered at 10 mg/kg Q6W or Q3W in combination with pembrolizumab (200 mg/Q3W) demonstrated an encouraging efficacy signal, durable disease control and an early survival benefit in MSS CRC patients, with dose-dependent efficacy and objective responses per RECIST criteria observed for the Q3W schedule:
- In the subset of efficacy evaluable patients without liver and peritoneal metastases (n=17) who received ADG126 10 mg/kg Q3W, an ORR of
24% was observed, including four confirmed PRs. These results are consistent with earlier ORR data published at ASCO GI 2024. Response rates for current standard of care treatments range from1% to6.3% *. - An additional 11 patients had stable disease (SD) for an overall disease control rate (DCR) of
88% (15/17). - Further, a median PFS of 8.5 months was observed in the subset at the ADG126 10 mg/kg Q3W dose and median PFS was 5.9 months for patients at the ADG126 10 mg/kg Q6W dose.
- The 12-month OS rates were
74% for those patients without liver metastases (n=36), and82% in those without liver and peritoneal metastases (n=24) in the combined 10 mg/kg Q6W and Q3W cohorts. - While the 10 mg/kg Q3W cohort demonstrated efficacy with RECIST responses and the Q6W did not, early OS rates appear comparable for both doses. This suggests that the Q6W could be used as a starting point for future combination trials, or as a dose modification strategy for safety management.
- Additionally, results in patients without liver metastases who received at least four cycles of the combination showed comparable OS rates to those without liver and peritoneal metastases, highlighting the importance of early disease control with standard of care to enable the IO doublet to drive a long-term survival benefit.
- In the subset of efficacy evaluable patients without liver and peritoneal metastases (n=17) who received ADG126 10 mg/kg Q3W, an ORR of
- In dose escalation, the 20 mg/kg Q3W dose level was tolerable for the initial cycle (n=6). Based upon the safety profile of the initial dose, 20 mg/kg is being evaluated as a loading dose in an expansion cohort that has enrolled 12 patients. This cohort is evaluating a single dose of ADG126 at 20 mg/kg followed by a 10 mg/kg Q3W maintenance dose in combination with pembrolizumab. Initial data for this cohort are expected later this year.
- Comprehensive PK and exposure response analyses were also conducted to provide insight on various dosing regimens and their correlation to safety and efficacy of the combination. These results reinforce the increased therapeutic index of ADG126, underscoring a key advantage of the SAFEbody® precision masking technology. The extensive PK data also guide future clinical development and dose selection to meet FDA’s Project Optimus dose optimization requirements.
Commenting on these promising results, Peter Luo, Adagene’s CEO and President of R&D said, “We are thrilled that today’s update continues to reinforce the clinical benefits of the best-in-class therapeutic potential for ADG126 at the 10 mg/kg dose level in combination with pembrolizumab in MSS CRC. Armed with these results and the anticipated findings from our ongoing 20 mg/kg loading dose regimen, we are moving ahead with plans to evaluate ADG126 in MSS CRC at 10- to 20-fold higher doses than ipilimumab in a randomized, registration-oriented clinical program. With safety comparable to historical data for pembrolizumab monotherapy, these data provide a solid foundation for the potential of an IO doublet targeting CTLA-4 and PD-1 to move into earlier lines of therapy and broader patient populations, particularly when combined with standard of care aiming for a transformational improvement in patient outcomes.”
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
SAFEbody® is a registered trademark in the United States, China, Australia, Japan, Singapore, and the European Union.
*Grothey et al. Lancet. 2013;381: 303-312; FDA label, 12/10/2020. Mayer et al. N Eng J Med. 2015;372: 1909-1919. Marcus et al. Clin Cancer Res; 23(12) June 15, 2017;2924-2927. Josep Tabernero et al. 2023 ASCO Gastrointestinal. Gerald W. Prager et al. N Engl J Med 2023 May 04;388(18). Shukui Qin et al. 2019 CSCO. Jin Li et al. JAMA. 2018;319(24): 2486-2496. Andrea J. Bullock et al. 2023 ESMO-GI. Anthony B et al. 2023 ASCO-GI. Elena et al. 2021 ASCO. E. Garralda et al. 2022 ESMO.
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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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.
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