Innovent Dosed First Participant in Phase 3 Clinical Study of IBI354 (Novel HER2 ADC) for Platinum-resistant Ovarian Cancer
Innovent Biologics (HKEX: 01801) has initiated dosing in a Phase 3 clinical trial (HeriCare-Ovarian01) of IBI354, a HER2 ADC, for platinum-resistant ovarian cancer (PROC). The study will compare IBI354 against standard chemotherapy, focusing on progression-free survival and overall survival as primary endpoints.
Previous Phase 1/2 results showed promising outcomes with IBI354:
- 40.2% overall objective response rate (ORR) and 81.6% disease control rate (DCR) across 87 PROC patients
- 52.5% ORR and 90.0% DCR in 40 patients treated with 12mg/kg dose
- 55.6% ORR and 88.9% DCR in HER2 IHC 1+ subjects at 12mg/kg
The drug demonstrated a favorable safety profile with 21.5% grade 3+ treatment-related adverse events, low discontinuation rates (1.6%), and no treatment-related deaths. Common side effects included nausea, decreased white blood cell count, and anemia.
Innovent Biologics (HKEX: 01801) ha avviato la somministrazione in uno studio clinico di Fase 3 (HeriCare-Ovarian01) di IBI354, un ADC HER2, per il cancro ovarico resistente al platino (PROC). Lo studio confronterà IBI354 con la chemioterapia standard, concentrandosi sulla sopravvivenza libera da progressione e sulla sopravvivenza complessiva come obiettivi primari.
I risultati precedenti di Fase 1/2 hanno mostrato esiti promettenti con IBI354:
- 40,2% di tasso di risposta obiettiva complessiva (ORR) e 81,6% di tasso di controllo della malattia (DCR) su 87 pazienti con PROC
- 52,5% di ORR e 90,0% di DCR in 40 pazienti trattati con una dose di 12mg/kg
- 55,6% di ORR e 88,9% di DCR in soggetti HER2 IHC 1+ a 12mg/kg
Il farmaco ha dimostrato un profilo di sicurezza favorevole con il 21,5% di eventi avversi correlati al trattamento di grado 3 o superiore, basse percentuali di interruzione (1,6%) e nessun decesso correlato al trattamento. Gli effetti collaterali comuni includevano nausea, diminuzione dei globuli bianchi e anemia.
Innovent Biologics (HKEX: 01801) ha iniciado la administración en un ensayo clínico de Fase 3 (HeriCare-Ovarian01) de IBI354, un ADC HER2, para el cáncer de ovario resistente al platino (PROC). El estudio comparará IBI354 con la quimioterapia estándar, centrándose en la supervivencia libre de progresión y la supervivencia general como puntos finales primarios.
Los resultados previos de Fase 1/2 mostraron resultados prometedores con IBI354:
- 40,2% de tasa de respuesta objetiva global (ORR) y 81,6% de tasa de control de la enfermedad (DCR) en 87 pacientes con PROC
- 52,5% de ORR y 90,0% de DCR en 40 pacientes tratados con una dosis de 12mg/kg
- 55,6% de ORR y 88,9% de DCR en sujetos HER2 IHC 1+ a 12mg/kg
El fármaco demostró un perfil de seguridad favorable con un 21,5% de eventos adversos relacionados con el tratamiento de grado 3 o superior, bajas tasas de discontinuación (1,6%) y ninguna muerte relacionada con el tratamiento. Los efectos secundarios comunes incluyeron náuseas, disminución del recuento de glóbulos blancos y anemia.
Innovent Biologics (HKEX: 01801)은 플래티넘 내성 난소암 (PROC)에 대한 HER2 ADC인 IBI354의 3상 임상 시험 (HeriCare-Ovarian01)에서 투약을 시작했습니다. 이 연구는 IBI354와 표준 화학요법을 비교하며, 주요 평가 지표로는 무진행 생존과 전체 생존을 설정하고 있습니다.
이전 1/2상 결과는 IBI354와 관련하여 유망한 결과를 보여주었습니다:
- 87명의 PROC 환자에서 40.2%의 전체 객관적 반응률 (ORR) 및 81.6%의 질병 조절률 (DCR)
- 12mg/kg 용량으로 치료받은 40명의 환자에서 52.5%의 ORR 및 90.0%의 DCR
- 12mg/kg에서 HER2 IHC 1+ 대상에서 55.6%의 ORR 및 88.9%의 DCR
이 약물은 21.5%의 3등급 이상의 치료 관련 부작용, 낮은 중단 비율 (1.6%), 치료 관련 사망자가 없다는 유리한 안전성 프로파일을 보여주었습니다. 일반적인 부작용으로는 메스꺼움, 백혈구 수 감소 및 빈혈이 포함되었습니다.
Innovent Biologics (HKEX: 01801) a commencé l'administration dans un essai clinique de Phase 3 (HeriCare-Ovarian01) de l'IBI354, un ADC HER2, pour le cancer de l'ovaire résistant au platine (PROC). L'étude comparera l'IBI354 à la chimiothérapie standard, en se concentrant sur la survie sans progression et la survie globale comme principaux critères d'évaluation.
Les résultats précédents des phases 1/2 ont montré des résultats prometteurs avec l'IBI354 :
- 40,2% de taux de réponse objective global (ORR) et 81,6% de taux de contrôle de la maladie (DCR) chez 87 patients atteints de PROC
- 52,5% d'ORR et 90,0% de DCR chez 40 patients traités avec une dose de 12mg/kg
- 55,6% d'ORR et 88,9% de DCR chez des sujets HER2 IHC 1+ à 12mg/kg
Le médicament a montré un profil de sécurité favorable avec 21,5% d'événements indésirables liés au traitement de grade 3 ou supérieur, de faibles taux d'interruption (1,6%) et aucun décès lié au traitement. Les effets secondaires courants comprenaient des nausées, une diminution du nombre de globules blancs et de l'anémie.
Innovent Biologics (HKEX: 01801) hat die Verabreichung in einer Phase-3-Studie (HeriCare-Ovarian01) zu IBI354, einem HER2-ADC, bei platin-resistentem Ovarialkarzinom (PROC) initiiert. Die Studie wird IBI354 mit der Standardchemotherapie vergleichen, wobei der Schwerpunkt auf dem progressionsfreien Überleben und dem Gesamtüberleben als primäre Endpunkte liegt.
Frühere Ergebnisse der Phase 1/2 zeigten vielversprechende Ergebnisse mit IBI354:
- 40,2% Gesamtansprechrate (ORR) und 81,6% Krankheitskontrollrate (DCR) bei 87 PROC-Patienten
- 52,5% ORR und 90,0% DCR bei 40 Patienten, die mit 12mg/kg behandelt wurden
- 55,6% ORR und 88,9% DCR bei HER2 IHC 1+ Probanden bei 12mg/kg
Das Medikament zeigte ein günstiges Sicherheitsprofil mit 21,5% Grad 3+ behandlungsbedingten unerwünschten Ereignissen, niedrigen Abbruchraten (1,6%) und keinen behandlungsbedingten Todesfällen. Häufige Nebenwirkungen umfassten Übelkeit, verminderten weißen Blutkörperchen und Anämie.
- Strong efficacy data with 40.2% ORR and 81.6% DCR in PROC patients
- Favorable safety profile with low discontinuation rate (1.6%) and no treatment-related deaths
- Effective in low HER2 expression patients (55.6% ORR in IHC 1+)
- Advancement to Phase 3 trial indicates development progress
- Phase 3 trial outcomes still pending and uncertain
- Median follow-up time of 6.5 months relatively short
- PFS and DoR data not yet mature
HeriCare-Ovarian01 is the first Phase 3 clinical trial (NCT06834672) in
Previously, in a multicenter Phase 1/2 study in participants with advanced solid tumors, a total of 87 participants with platinum-resistant ovarian cancer were enrolled and were treated with 6-12 mg/kg doses of IBI354. 67 (
- As of July 24, 2024, the overall objective response rate (ORR) was
40.2% and the disease control rate (DCR) was81.6% . - Among them, ORR reached
52.5% and DCR reached90.0% in 40 ovarian cancer participants treated with 12mg/kg Q3W - ORR reached
55.6% and DCR reached88.9% in 27 subjects with HER2 IHC 1+ (12mg/kg Q3W dose group). - The median follow-up time of 12mg/kg Q3W dose group was 6.5 months as of the cut-off date, and progression-free survival (PFS) and duration of response (DoR) were not mature. The data was presented at the ESMO conference.
In the phase 1/2 clinical study (n=368), IBI354 demonstrated an excellent safety profile.
- No DLT was occurred up to 18mg/kg dose group.
- The overall incidence of grade 3 or higher treatment-related adverse events (TRAEs) was
21.5% , the incidence of TRAEs leading to dose interruption was12.2% , the incidence of TRAEs leading to dose reduction was2.4% , the overall incidence of TRAEs leading to discontinuation was1.6% , and no TRAE leading to death reported. - The most common TRAEs are nausea, white blood cell count decreased, and anemia. The incidence of interstitial lung disease was only
1.6% , all were grade 1.
The Principal Investigator of the HeriCare-Ovarian01 study, Prof. Qi Zhou from Chongqing University Cancer Hospital, stated, "Prolonging PFS and OS of PROC is an urgent unmet medical need. Ovarian cancer is characterized by a pattern of frequent recurrence, which ultimately leads to platinum resistance. Non-platinum monotherapy chemotherapy remains the primary treatment option at this stage, but its limited efficacy is a major contributor to the high mortality rate associated with ovarian cancer. As a fully-validated target, HER2-targeted therapy has proven effective in breast and gastric cancers. IBI354, as a innovative conjugate of anti-HER2 monoclonal antibody and camptothecin derivative, has shown good anti-tumor activity in PROC with HER2 expression in the previous study. Especially in the population with low HER2 expression (IHC 1+), the efficacy of IBI354 is comparable to that in the population with higher HER2 expression. At the same time, IBI354 has an excellent safety profile, showing a very low risk of common or concerned toxicities of other antibody-drug conjugates (ADCs), such as interstitial lung disease, fatigue, diarrhea, hair loss, eye toxicity, etc. I look forward to positive results from the HeriCare-Ovarian01 study. It is hoped that IBI354 may provide survival benefits to the PROC patients with varying levels of HER2 expression."
The Principal Collaborating Investigator of the study from Zhejiang Cancer Hospital, Prof. Tao Zhu, stated: "We are pleased to complete the first patient enrollment for the HeriCare-Ovarian01 study at our site. Although ovarian cancer ranks third among gynecologic malignancies in incidence, behind cervical and endometrial cancers, its mortality rate exceeds the combined total of the latter two, making it the deadliest gynecologic cancer and a severe threat to women's health. As an anti-HER2 ADC, preliminary findings from IBI354 have demonstrated encouraging objective response rates (ORR) and disease control rates (DCR) in PROC. Furthermore, IBI354 exhibits a superior clinical safety profile and treatment tolerability compared to other ADCs. Current clinical data suggest promising development prospects for IBI354 in PROC. We are hopeful that IBI354 will achieve success in the HeriCare-Ovarian01 study, offering new therapeutic options for this patient population."
Dr. Zhou Hui, Senior Vice President of Innovent, stated, "I'm pleased that the Phase III clinical study of IBI354 in HER2-expressing PROC has completed the first participant dosing. I look forward to positive results for IBI354 to provide a better treatment option for patients with HER2-expressing PROC. ADC is one of the core technology areas of Innovent's strategic layout. We combine the world's leading antibody engineering and multiple sets of differentiated linker-payload technologies to create a highly competitive and innovative TOPO1i ADC technology platform SoloTx®. IBI354 has demonstrated excellent safety and efficacy data in the previous study, which fully proves the value and the development strength of Innovent ADC platform. We will deeply layout the ADC and immunotherapy areas, focusing on the next generation of innovation, committed to bring better benefits to cancer patients."
About Ovarian Cancer
OC is one of the leading causes of death among gynecological cancers. According to the International Agency for Research on Cancer, there will be about 324,000 new cases of ovarian cancer worldwide in 2022, and about 206,000 deaths[1]. About 61,000 new cases and 33,000 deaths were reported in
About IBI354
IBI354 is an innovative HER2-targeted antibody–drug conjugate developed using Innovent's proprietary novel topoisomerase inhibitor platform. Based on this platform, Innovent is promoting clinical trial studies multiple self-developed ADC molecules, which have shown promising safety and efficacy signals.
With a drug-to-antibody ratio (DAR) of 8, IBI354 delivers a high payload of effective drugs to tumors. The highly hydrophilic linker design contributes to its excellent biophysical and pharmacokinetic (PK) properties, while the hydrophobic payload enhances its bystander effect, targeting adjacent antigen-low or negative tumor cells. IBI354 exhibits extremely low exposure of free toxin in circulation and has an ideal safety profile based on pre-clinical and clinical studies. IBI354 has demonstrated remarkable anti-tumor activity in various tumor-bearing mice models, particularly in those resistant to HER2-targeted therapies and in metastatic tumors.
Starting from the urgent clinical needs, in addition to the phase III study (HeriCare-Ovarian01) already initiated in PROC, Innovent will develop IBI354 in multiple solid tumor indications.
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 15 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 15 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.
Statement:
1) Innovent does not recommend the use of any unapproved drug (s)/indication (s).
2) Ramucirumab (Cyramza) and Selpercatinib (Retsevmo) and Pirtobrutinib (Jaypirca) were developed by Eli Lilly and Company.
Disclaimer: Innovent does not recommend any off-label usage.
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.
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FAQ
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