Innovent Announces Clinical Data of IBI363 (First-in-class PD-1/IL-2α-bias Bispecific Antibody Fusion Protein) Combined with Bevacizumab in Advanced Colorectal Cancer at the 2024 ESMO Congress
Innovent Biologics (HKEX: 01801) presented clinical data for IBI363, a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein, combined with bevacizumab in advanced colorectal cancer at the 2024 ESMO Congress. The Phase 1 study involved 35 subjects, showing promising anti-tumor efficacy with good tolerability. Key findings include:
- 21.9% overall response rate (ORR) and 65.6% disease control rate (DCR)
- Median duration of response: 8.1 months
- Median progression-free survival: 4.1 months
- Efficacy observed in patients with and without liver metastases, prior immunotherapy, and RAS mutations
The combination demonstrated potential in non-MSI-H/dMMR advanced colorectal cancer, a population typically less responsive to immunotherapy. Innovent is conducting further Phase 1/2 trials in China, the US, and Australia for various solid tumors.
Innovent Biologics (HKEX: 01801) ha presentato dati clinici per IBI363, una proteina fusione bispecifica PD-1/IL-2α-bias di prima classe, combinata con bevacizumab per il trattamento del cancro colorettale avanzato durante il Congresso ESMO 2024. Lo studio di Fase 1 ha coinvolto 35 soggetti, mostrando una promettente efficacia antitumorale con buona tollerabilità. I risultati chiave includono:
- 21,9% tasso di risposta complessivo (ORR) e 65,6% tasso di controllo della malattia (DCR)
- Durata mediana della risposta: 8,1 mesi
- Sopravvivenza libera da progressione mediana: 4,1 mesi
- Efficacia osservata in pazienti con e senza metastasi epatiche, precedenti immunoterapie e mutazioni RAS
La combinazione ha dimostrato potenziale nel cancro colorettale avanzato non MSI-H/dMMR, una popolazione tipicamente meno reattiva all'immunoterapia. Innovent sta conducendo ulteriori studi di Fase 1/2 in Cina, negli Stati Uniti e in Australia per vari tumori solidi.
Innovent Biologics (HKEX: 01801) presentó datos clínicos para IBI363, un anticuerpo fusionado bispecífico de clase inaugural PD-1/IL-2α-bias, combinado con bevacizumab en cáncer colorrectal avanzado en el Congreso ESMO 2024. El estudio de Fase 1 involucró a 35 sujetos, mostrando una prometedora eficacia antitumoral con buena tolerancia. Los hallazgos clave incluyen:
- 21,9% de tasa de respuesta general (ORR) y 65,6% de tasa de control de la enfermedad (DCR)
- Duración media de la respuesta: 8,1 meses
- Supervivencia libre de progresión media: 4,1 meses
- Eficacia observada en pacientes con y sin metástasis hepáticas, terapia inmunitaria previa y mutaciones RAS
La combinación demostró potencial en cáncer colorrectal avanzado no MSI-H/dMMR, una población típicamente menos receptiva a la inmunoterapia. Innovent está llevando a cabo más ensayos de Fase 1/2 en China, EE. UU. y Australia para varios tumores sólidos.
Innovent Biologics (HKEX: 01801)은 2024년 ESMO 총회에서 말기 대장암 치료의 일환으로 bevacizumab과 결합된 1세대 PD-1/IL-2α-비편향 이중 특이성 항체 융합 단백질 IBI363의 임상 데이터를 발표했습니다. 1상 연구는 35명의 피험자를 포함하였으며, 우수한 내약성과 함께 유망한 항종양 효능을 보여주었습니다. 주요 결과는 다음과 같습니다:
- 전체 반응률(ORR): 21.9%, 질병 조절률(DCR): 65.6%
- 반응 지속 시간 중앙값: 8.1개월
- 무진행 생존 중앙값: 4.1개월
- 간전이를 가진 환자와 없는 환자, 이전 면역 요법을 받은 환자 및 RAS 변이를 가진 환자 모두에서 효과가 관찰됨
이 조합은 면역 요법에 덜 반응하는 군에서 일반적으로 유효성이 적은 비MSI-H/dMMR 말기 대장암에서 잠재력을 보여 주었습니다. Innovent는 중국, 미국 및 호주에서 다양한 고형종양에 대한 추가 1/2상 시험을 진행하고 있습니다.
Innovent Biologics (HKEX: 01801) a présenté des données cliniques sur IBI363, une protéine de fusion d'anticorps bispécifique de première classe PD-1/IL-2α-biais, combinée avec bevacizumab pour le cancer colorectal avancé lors du Congrès ESMO 2024. L'étude de Phase 1 a impliqué 35 sujets, montrant une efficacité anti-tumorale prometteuse avec une bonne tolérance. Les résultats clés incluent :
- Taux de réponse global (ORR) de 21,9 % et taux de contrôle de la maladie (DCR) de 65,6 %
- Durée médiane de la réponse : 8,1 mois
- Durée médiane de survie sans progression : 4,1 mois
- Efficacité observée chez des patients avec et sans métastases hépatiques, avec antécédents d'immunothérapie et mutations RAS
La combinaison a montré un potentiel dans le cancer colorectal avancé non MSI-H/dMMR, une population généralement moins réactive à l'immunothérapie. Innovent réalise d'autres essais de Phase 1/2 en Chine, aux États-Unis et en Australie pour divers tumeurs solides.
Innovent Biologics (HKEX: 01801) präsentierte klinische Daten zu IBI363, einem erstklassigen bispezifischen Antikörper-Fusionsprotein mit PD-1/IL-2α-Bias, in Kombination mit Bevacizumab zur Behandlung von fortgeschrittenem Kolorektalkrebs auf dem ESMO-Kongress 2024. Die Phase-1-Studie umfasste 35 Probanden und zeigte vielversprechende anti-tumorale Wirksamkeit bei guter Verträglichkeit. Die wichtigsten Ergebnisse sind:
- 21,9% Gesamtansprechrate (ORR) und 65,6% Krankheitskontrollrate (DCR)
- Median der Ansprechdauer: 8,1 Monate
- Median des progressionsfreien Überlebens: 4,1 Monate
- Wirksamkeit beobachtet bei Patienten mit und ohne Lebermetastasen, vorheriger Immuntherapie und RAS-Mutationen
Die Kombination zeigte Potenzial bei nicht MSI-H/dMMR fortgeschrittenem Kolorektalkrebs, einer Gruppe, die typischerweise weniger auf Immuntherapien reagiert. Innovent führt weitere Phase-1/2-Studien in China, den USA und Australien für verschiedene solide Tumoren durch.
- 21.9% overall response rate (ORR) and 65.6% disease control rate (DCR) in advanced colorectal cancer patients
- Median duration of response of 8.1 months, indicating durable responses
- Efficacy observed in both immunotherapy-treated and immunotherapy-naïve patients
- Promising results in patients with and without liver metastases
- Manageable safety profile with no new safety signals identified
- 22.9% incidence of treatment-related adverse events ≥ grade 3
- 5.7% of subjects experienced immune-related adverse events ≥ grade 3
- Median progression-free survival of 4.1 months, which may be considered modest
SAN FRANCISCO and
First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein IBI363 combined with bevacizumab in patients with advanced colorectal cancer: Results from Phase 1 study
This Phase 1 study was conducted to evaluate the safety, tolerability and preliminary efficacy of IBI363 combined with bevacizumab in subjects with advanced colorectal cancer.
A total of 35 subjects received treatment of IBI363 combined with bevacizumab, demonstrating promising anti-tumor efficacy with good tolerability and safety
- As of the data cutoff date (Aug 30, 2024), a total of 35 subjects with advanced colorectal cancer received combination treatment at 3 different dose levels (0.6 mg/kg IBI363 combined with 5 mg/kg bevacizumab Q2W, 1 mg/kg IBI363 combined with 5 mg/kg bevacizumab Q2W, and 1.5 mg/kg IBI363 combined with 7.5 mg/kg bevacizumab Q3W). Among them,
91.4% of the subjects had advanced colorectal cancer with microsatellite stable (MSS) or proficient mismatch repair (pMMR), and the MSI/MMR status was unknown in8.6% subjects.91.4% of the subjects had previously received 2 or more lines of systemic anti-tumor treatment.51.4% of the subjects had liver metastases.25.7% of the subjects had received prior immunotherapy.40% of the subjects had KRAS/NRAS exon 2/3/4 mutations. - The most common treatment related adverse events (TRAEs) were arthralgia, thyroid disorders, and rash. The total incidence of TRAEs ≥ grade 3 was
22.9% . Immune related adverse events (irAEs) ≥ grade 3 occurred in5.7% of subjects. The safety profile of the combination regimen was similar to that of IBI363 monotherapy, and no new safety signals were identified.
Promising anti-tumor activity in subjects with MSS/pMMR colorectal cancer; durable responses with a trend towards long-term benefit
- As of the cutoff date, 32 subjects were efficacy evaluable having underwent at least one post-baseline tumor assessment. The ORR was
21.9% (confirmed ORR was15.6% ), and DCR was65.6% . The median DoR was 8.1 months (95% CI: 1.5~8.2). The median PFS follow-up time was 7.6 months (95% CI: 4.0~9.4), and the median PFS was 4.1 months (95% CI: 1.7~8.1). The median OS was not reached.
Promising efficacy signals in colorectal cancer with and without baseline liver metastases
- Among the 17 subjects with baseline liver metastases who underwent at least one post-baseline tumor assessment, ORR was
11.8% and DCR was58.8% . - Among the 15 subjects without baseline liver metastases who underwent at least one post-baseline tumor assessment, ORR was
33.3% and DCR was73.3% .
Promising efficacy signals in both IO-treated and IO-naïve colorectal cancer
- Among the 8 subjects who had received prior immunotherapy and underwent at least one post-baseline tumor assessment, ORR was
25.0% and DCR was62.5% . - Among the 24 IO-naïve subjects who underwent at least one post-baseline tumor assessment, ORR was
20.8% and DCR was66.7% .
Promising efficacy signals in colorectal cancer with and without KRAS/NRAS exon 2/3/4 mutations
- Among the 14 subjects with RAS exon 2/3/4 mutations and who had undergone at least one post-baseline tumor assessment, ORR was
21.4% and DCR was57.1% . - Among the 10 subjects without RAS exon 2/3/4 mutations who had undergone at least one post-baseline tumor assessment, ORR was
30.0% and DCR was90.0% .
In addition, data from a Phase 1 clinical study of IBI363 monotherapy in a colorectal cancer cohort, presented at ASCO 2024, showed promising efficacy and good tolerability. Ongoing studies are now exploring IBI363 in other malignancies, including NSCLC, melanoma and other solid tumors, as well as in combination regimens for MSS/pMMR advanced colorectal cancer. Updates on relevant data and analysis will be shared at upcoming academic conferences and in journals.
Professor Tao Zhang, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, stated: "Colorectal cancer is the third most common cancer type globally and ranks fourth in cancer-related mortality[1]. Despite recent advancements in colorectal cancer treatment, challenges such as chemotherapy toxicity and resistance continue to affect patients and clinicians. While immunotherapy offers new hope for advanced colorectal cancer patients, it is currently only approved for those with MSI-H/dMMR tumors. Research indicates that immunotherapy has limited efficacy in non-MSI-H/dMMR advanced colorectal cancer[2]. As an important cytokine activating tumor-specific CD8+T cells, IL-2 is complementary to immune checkpoint inhibitors in MOA. The combination of PD-1 and IL-2 may reverse the exhaustion of tumor-specific CD8+ T cells thereby overcoming immune resistance. The PD-1/IL-2α-bias bispecific molecule IBI363, when combined with bevacizumab, has shown promising anti-tumor activity in patients with non-MSI-H/dMMR advanced colorectal cancer. This combination has shown clinical benefits in both ORR and PFS, and maintains a manageable safety profile. Additionally, the combination regimen has proven effective in colorectal cancer patients with or without liver metastasis, prior immunotherapy, and RAS exon 2/3/4 mutations. IBI363 combined with bevacizumab elicited encouraging objective response rates and disease control rates, with durable responses and a trend towards long-term benefits, without introducing new safety risks in a colorectal cancer population that has previously shown very little response to immunotherapy. Overall, current clinical data suggest that IBI363 combined with bevacizumab holds significant promise for colorectal cancer and deserves further exploration."
Dr. Hui Zhou, Senior Vice President of Innovent, stated: "On top of the preliminary data reported at ASCO, we are presenting more updated data at the ESMO Congress. In non-MSI-H/dMMR advanced colorectal cancer, the combination of IBI363 with bevacizumab has demonstrated strong anti-tumor effects, with durable responses and a trend towards long-term benefits. These promising results in a relatively 'cold' tumor suggest significant potential for IBI363 in this disease area. We are confident in the broad development prospects of IBI363 and look forward to seeing more mature data from higher doses and extended follow-up, which will help us advance to the next stage of clinical development."
About IBI363 (First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein)
IBI363 is a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein independently developed by Innovent Biologics. It functions by both blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway. The IL-2 arm of IBI363 is designed to maintain its affinity for IL-2Rα while reducing binding to IL-2Rβ and IL-2Rγ, thereby minimizing toxicity. The PD-1 binding arm not only blocks PD-1 but also selectively delivers IL-2. This approach targets and activates tumor-specific T cells that express both PD-1 and IL-2α, leading to more precise and effective activation of this T cell subpopulation. IBI363 has demonstrated robust antitumor activity in various tumor-bearing pharmacological models, but also showed outstanding efficacy in PD-1 resistance and metastasis models. In response to urgent clinical needs, Innovent is conducting clinical studies in
About Innovent
Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 11 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.
Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.
Forward-Looking Statements
This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.
These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.
Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.
References |
1. https://publications.iarc.fr/Databases/Iarc-Cancerbases/GLOBOCAN-2012-Estimated-Cancer-Incidence-Mortality-And-Prevalence-Worldwide-In-2012-V1.0-2012. |
2. Baraibar I, Mirallas O, Saoudi N et al. Combined Treatment with Immunotherapy-Based Strategies for MSS Metastatic Colorectal Cancer. Cancers ( |
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