New Data Demonstrated Best-in-Class Potential for Casdatifan, a HIF-2a Inhibitor, in Patients with Metastatic Kidney Cancer
Arcus Biosciences (NYSE:RCUS) presented new data for casdatifan, their HIF-2a inhibitor for metastatic kidney cancer, showing promising results across three monotherapy cohorts. The 50mg twice-daily cohort achieved a 9.7-month median progression-free survival, while other cohorts had not yet reached their median.
Key findings include a 33% confirmed response rate in the 100mg cohort using tablet formulation, which is the expected go-forward dose for pivotal studies. Across all cohorts, 81-87% of patients experienced disease control with either partial response or stable disease. The study involved heavily pretreated patients, with 52-59% having received at least three prior lines of therapy.
Casdatifan demonstrated an acceptable safety profile, with low discontinuation rates. The company plans to advance the drug through multiple development programs, including the Phase 3 PEAK-1 study in combination with cabozantinib.
Arcus Biosciences (NYSE:RCUS) ha presentato nuovi dati su casdatifan, il loro inibitore HIF-2a per il cancro renale metastatico, mostrando risultati promettenti in tre coorti di monoterapia. La coorte da 50 mg due volte al giorno ha raggiunto una mediana di sopravvivenza libera da progressione di 9,7 mesi, mentre le altre coorti non avevano ancora raggiunto la loro mediana.
I principali risultati includono un tasso di risposta confermato del 33% nella coorte da 100 mg con formulazione in compresse, che è la dose prevista per gli studi pivotal. In tutte le coorti, l'81-87% dei pazienti ha sperimentato un controllo della malattia con risposta parziale o malattia stabile. Lo studio ha coinvolto pazienti pesantemente pretrattati, con il 52-59% che aveva ricevuto almeno tre linee di terapia precedenti.
Casdatifan ha dimostrato un profilo di sicurezza accettabile, con basse percentuali di interruzione del trattamento. L'azienda prevede di avanzare il farmaco attraverso diversi programmi di sviluppo, incluso lo studio di Fase 3 PEAK-1 in combinazione con cabozantinib.
Arcus Biosciences (NYSE:RCUS) presentó nuevos datos sobre casdatifan, su inhibidor de HIF-2a para el cáncer de riñón metastásico, mostrando resultados prometedores en tres cohortes de monoterapia. La cohorte de 50 mg dos veces al día logró una mediana de supervivencia libre de progresión de 9.7 meses, mientras que las otras cohortes aún no habían alcanzado su mediana.
Los hallazgos clave incluyen una tasa de respuesta confirmada del 33% en la cohorte de 100 mg usando formulación en tabletas, que es la dosis esperada para estudios pivotal. En todas las cohortes, el 81-87% de los pacientes experimentó control de la enfermedad con respuesta parcial o enfermedad estable. El estudio involucró a pacientes con un alto nivel de tratamiento previo, con un 52-59% que había recibido al menos tres líneas de terapia anteriores.
Casdatifan demostró un perfil de seguridad aceptable, con bajas tasas de interrupción. La empresa planea avanzar el fármaco a través de múltiples programas de desarrollo, incluyendo el estudio de Fase 3 PEAK-1 en combinación con cabozantinib.
아르쿠스 바이오사이언스(뉴욕증권거래소:RCUS)는 전이성 신장암을 위한 HIF-2a 억제제인 casdatifan에 대한 새로운 데이터를 발표하며, 세 가지 단독 요법 집단에서 유망한 결과를 보여주었습니다. 하루 두 번 50mg 투여 집단은 9.7개월의 중앙 무진행 생존 기간을 달성했으며, 다른 집단은 아직 중앙값에 도달하지 못했습니다.
주요 발견 중 하나는 정제 형태의 100mg 집단에서 33%의 확정된 반응률을 보였으며, 이는 주요 연구에서 사용할 예상 용량입니다. 모든 집단에서 81-87%의 환자가 부분 반응 또는 안정된 질병을 경험하며 질병 조절을 이루었습니다. 이번 연구는 치료를 많이 받은 환자들을 대상으로 하였으며, 52-59%는 최소 세 가지 이전 치료를 받은 경험이 있었습니다.
Casdatifan은 낮은 중단율로 수용 가능한 안전성 프로파일을 보여주었습니다. 회사는 cabozantinib과의 병용으로 진행되는 3상 PEAK-1 연구를 포함하여 다양한 개발 프로그램을 통해 약물을 진전시킬 계획입니다.
Arcus Biosciences (NYSE:RCUS) a présenté de nouvelles données sur le casdatifan, leur inhibiteur de HIF-2a pour le cancer du rein métastatique, montrant des résultats prometteurs dans trois cohortes de monothérapie. La cohorte de 50 mg administrée deux fois par jour a atteint une médiocre de survie sans progression de 9,7 mois, tandis que les autres cohortes n'avaient pas encore atteint leur médiane.
Les résultats clés incluent un taux de réponse confirmé de 33% dans la cohorte de 100 mg utilisant une formulation en comprimés, qui est la dose prévue pour les études pivot. Dans toutes les cohortes, 81-87% des patients ont connu un contrôle de la maladie avec soit une réponse partielle, soit une maladie stable. L'étude a impliqué des patients ayant reçu de nombreux traitements antérieurs, avec 52-59% ayant reçu au moins trois lignes de thérapie antérieures.
Le casdatifan a démontré un profil de sécurité acceptable, avec de faibles taux d'abandon. L'entreprise prévoit de faire avancer le médicament à travers plusieurs programmes de développement, y compris l'étude de Phase 3 PEAK-1 en combinaison avec le cabozantinib.
Arcus Biosciences (NYSE:RCUS) präsentierte neue Daten zu casdatifan, ihrem HIF-2a-Inhibitor für metastasierenden Nierenkrebs, und zeigte vielversprechende Ergebnisse in drei Monotherapie-Kohorten. Die Kohorte mit 50 mg zweimal täglich erreichte eine medianen progressionsfreien Überlebenszeit von 9,7 Monaten, während die anderen Kohorten ihre Medianwerte noch nicht erreicht hatten.
Wesentliche Erkenntnisse umfassen eine bestätigte Ansprechrate von 33% in der Kohorte mit 100 mg in Tablettenform, die die erwartete Dosis für entscheidende Studien ist. In allen Kohorten erlebten 81-87% der Patienten eine Krankheitskontrolle mit entweder teilweiser Reaktion oder stabiler Erkrankung. Die Studie umfasste stark vorbehandelte Patienten, wobei 52-59% mindestens drei vorherige Therapielinien erhalten hatten.
Casdatifan zeigte ein akzeptables Sicherheitsprofil mit niedrigen Abbruchraten. Das Unternehmen plant, das Medikament durch mehrere Entwicklungsprogramme voranzutreiben, einschließlich der Phase-3-Studie PEAK-1 in Kombination mit Cabozantinib.
- Achieved 9.7-month median progression-free survival in 50mg BID cohort
- 33% confirmed response rate in 100mg tablet cohort
- 81-87% disease control rate across all cohorts
- Low treatment discontinuation rate (only 3 patients total)
- Most responders (24 out of 26) still on treatment at data cutoff
- Majority of patients experienced Grade ≥3 treatment-related adverse events (notably anemia and hypoxia)
- No complete responses in two of three cohorts
Insights
The latest data from the ARC-20 study reveals compelling evidence of casdatifan's potential as a best-in-class HIF-2a inhibitor in metastatic kidney cancer. The drug demonstrated remarkable efficacy across multiple dosing regimens, with the 100mg QD tablet formulation achieving a
Several aspects of the data stand out as particularly significant:
- The disease control rate of
81-87% across cohorts indicates robust clinical activity - Most responders (24 out of 26) remained on treatment at data cutoff, suggesting durable benefits
- The safety profile appears superior to existing treatments, with notably low discontinuation rates due to adverse events
The planned Phase 3 PEAK-1 study, evaluating casdatifan in combination with cabozantinib, represents a strategic approach to expanding the drug's potential market reach. The collaboration with AstraZeneca to study combination therapy with volrustomig further strengthens the commercial prospects. These developments position Arcus competitively in the evolving kidney cancer treatment landscape, where there remains significant unmet need for effective therapies in both first-line and refractory settings.
- A 9.7-month median progression-free survival (mPFS) was reached for the 50mg twice-daily (BID) casdatifan monotherapy cohort of the Phase 1/1b ARC-20 study; mPFS was not yet reached for other cohorts
- Across all three monotherapy cohorts presented, casdatifan demonstrated improvements in the rate of primary progression, overall response rate (ORR) and progression-free survival (PFS) relative to published data from studies with HIF-2a inhibitors to date
- Arcus will host a conference call to discuss these data at 5:00 AM PT / 8:00 AM ET on Tuesday, February 18, 2025
“The newest data are from the 100mg cohort using the tablet formulation and the expected go-forward dose for pivotal studies, which showed a
ARC-20 is a Phase 1/1b dose-escalation and expansion study. New data include mPFS and ORR for the 50mg BID cohort, and ORR for the 50mg once-daily (QD) and 100mg QD (tablet) cohorts, all of which evaluated casdatifan in patients with metastatic clear cell renal cell carcinoma (ccRCC), most of whom had progressed on at least two prior lines of therapy, including both an anti-PD-1 and a VEGFR tyrosine kinase inhibitor (TKI) therapy. The patient population was heavily pretreated; more than half (52
Casdatifan showed improvement in primary progressive disease rate (progressed at or before their first disease assessment), ORR and mPFS relative to published data from studies with HIF-2a inhibitors to date. At the time of data cut off (DCO, January 3, 2025), most patients (81
No unexpected safety signals were observed at the time of DCO, and casdatifan had an acceptable and manageable safety profile across all doses. Across all three cohorts, only one patient discontinued treatment as a result of anemia and only two due to hypoxia. A summary of the efficacy and safety results is below.
|
50mg BID (n=32) |
50mg QD (n=28) |
100mg QD Tablet (Go-forward dose) (n=27) |
Efficacya |
|||
Median Follow-Up |
15 months |
12 months |
5 monthsb |
Median Progression-Free Survival ( |
9.7 months (5.5, NE) |
NE (6.8, NE) |
NE |
Confirmed ORR (cORR) per RECIST v1.1 [ |
[11.5-43.4] |
[15.9-52.4] |
[16.5-54.0] |
Best Overall Responsed: |
|
|
|
Complete Response |
0 |
|
0 |
Partial Response |
|
|
|
Stable Disease |
|
|
|
Progressive Disease |
|
|
|
Median Time to Response |
2.8 months |
4.1 months |
1.6 months |
Disease Control Rate
[ |
[63.6-92.8] |
[67.3-96.0] |
[66.3-95.8] |
CI: confidence interval; NE: not estimable
a Efficacy-evaluable population for this expansion cohort is defined as all eligible participants who received any study treatment and have at least one post-baseline efficacy assessment, or who discontinued study treatment due to progressive disease or death.
b Majority of patients (n=21) were still on treatment at time of DCO.
c In the 50mg BID cohort, one unconfirmed responder remains on treatment. In the 50mg QD cohort, one unconfirmed responder became a confirmed responder after the DCO, increasing the cORR to
d Unconfirmed best overall response.
e Includes two patients with radiological progressive disease and two patients who had clinical progression before the first scan.
|
50mg BID (n=33) |
50mg QD (n=31) |
100mg QD Tablet (Go-forward dose) (n=29) |
Safetya |
|||
Any Serious Treatment-Emergent Adverse Events (TEAEs) related to casdatifan |
|
|
|
Grade ≥3 TEAEs related to casdatifan |
|
|
|
|
|
|
|
Anemia |
|
|
|
Hypoxia |
|
|
|
a The safety-evaluable population included all dose expansion enrolled patients who received any amount of any study treatment.
Arcus is pursuing a broad development program in both the immuno-oncology (IO)-naive and post-IO settings with differentiated combinations to maximize the opportunity for casdatifan in ccRCC. These studies include:
- Arcus’s planned Phase 3 study, PEAK-1, which will evaluate casdatifan in combination with cabozantinib versus cabozantinib monotherapy as a first- or second-line treatment in patients with metastatic ccRCC who have previously received anti-PD-1 therapy. The primary endpoint will be PFS with a key secondary endpoint of overall survival.
- A planned Phase 1b study operationalized by AstraZeneca (part of the eVOLVE portfolio) to evaluate casdatifan in combination with volrustomig, an investigational anti-PD-1/CTLA-4 bispecific antibody.
- Initiation of two additional cohorts in ARC-20 to evaluate casdatifan in first-line settings.
Investors may dial in to the conference call at +1 404 975 4839 (local) or +1 833 470 1428 (toll-free) using Conference ID: 331780 on Tuesday, February 18, 2025, at 5:00 AM PT / 8:00 AM ET. Participants may also register for the call online using the following link: https://events.q4inc.com/attendee/364282703. To access the live webcast and accompanying slide presentation, please visit the “Investors & Media” section of the Arcus Biosciences website at www.arcusbio.com. A replay will be available following the live event.
About Casdatifan (AB521)
Casdatifan is a small-molecule inhibitor of HIF-2a, a transcription factor responsible for activating multiple tumor growth pathways in hypoxic and pseudo-hypoxic tumor environments. By selectively binding HIF-2a, casdatifan is designed to shut down hypoxic oncogenesis and key oncogenic pathways leading to cancer cell death. Clear cell RCC (ccRCC) is almost universally associated with HIF-2a dysregulation. Casdatifan is currently being evaluated in ARC-20, a Phase 1/1b study in renal cell carcinoma and other cancers.
Casdatifan is an investigational molecule. Approval from any regulatory authority for its use has not been received, and its safety and efficacy have not been established.
About RCC
According to the American Cancer Society, kidney cancer is among the top 10 most commonly diagnosed forms of cancer among both men and women in the
About Arcus Biosciences
Arcus Biosciences is a clinical-stage, global biopharmaceutical company developing differentiated molecules and combination medicines for people with cancer. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of first- or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has expedited the development of multiple investigational medicines into clinical studies, including new combination approaches that target TIGIT, PD-1, HIF-2a, CD73, dual A2a/A2b receptor, CD39 and AXL. For more information about Arcus Biosciences’s clinical and preclinical programs, please visit www.arcusbio.com.
Forward Looking Statements
This press release contains forward-looking statements. All statements regarding events or results to occur in the future contained herein are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, the statements in Dr. Markus’s quotes and statements regarding: the potency, efficacy or safety of casdatifan, including its potential for a best-in-class profile and potential as a combination therapy; and Arcus’s development plans for the casdatifan program, including expected timing and design for new studies and cohorts and plans for generating data to support initiation of future studies. All forward-looking statements involve known and unknown risks and uncertainties and other important factors that may cause Arcus’s actual results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to risks associated with: interim data not being replicated in future studies evaluating the same investigational molecules or regimen; the unexpected emergence of adverse events or other undesirable side effects with casdatifan; risks associated with manufacturing or supplying product for such clinical trials; uncertainties in timelines associated with the conduct of clinical studies and with respect to the regulatory application process; difficulties associated with the management of the collaboration activities with our strategic partners or expanded clinical programs; changes in the competitive landscape for Arcus’s programs; and the inherent uncertainty associated with pharmaceutical product development and clinical trials. Risks and uncertainties facing Arcus are described more fully in the “Risk Factors” section of Arcus’s most recent periodic report filed with the
The Arcus name and logo are trademarks of Arcus Biosciences, Inc. All other trademarks belong to their respective owners.
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Investor Inquiries:
Pia Eaves
VP of Investor Relations & Strategy
(617) 459-2006
peaves@arcusbio.com
Media Inquiries:
Holli Kolkey
VP of Corporate Affairs
(650) 922-1269
hkolkey@arcusbio.com
Maryam Bassiri
AD, Corporate Communications
(510) 406-8520
mbassiri@arcusbio.com
Source: Arcus Biosciences
FAQ
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