First Clinical Data for Arcus Biosciences’ HIF-2a Inhibitor, Casdatifan, Showed Promising Clinical Activity and Tumor Shrinkage in Patients with Metastatic Kidney Cancer
Arcus Biosciences presented promising first clinical data for casdatifan, their HIF-2a inhibitor, in treating metastatic kidney cancer. The Phase 1/1b study (ARC-20) showed a 34% objective response rate (2 responses pending confirmation) and 25% confirmed response rate in the 100mg daily dose expansion cohort of 32 patients. The treatment demonstrated an 81% disease control rate with only 19% primary progression. Safety profile was manageable, with Grade 3 treatment-related adverse events at 42%, mainly including anemia (36%) and hypoxia (9%). The company plans to initiate PEAK-1, their first Phase 3 study, in the first half of 2025.
Arcus Biosciences ha presentato dati clinici promettenti per casdatifan, il loro inibitore HIF-2a, nel trattamento del cancro renale metastatico. Lo studio di Fase 1/1b (ARC-20) ha mostrato un tasso di risposta obiettivo del 34% (2 risposte in attesa di conferma) e un tasso di risposta confermata del 25% nel gruppo di espansione a dosaggio di 100 mg al giorno di 32 pazienti. Il trattamento ha dimostrato un tasso di controllo della malattia dell'81% con solo il 19% di progressione primaria. Il profilo di sicurezza è stato gestibile, con eventi avversi correlati al trattamento di Grado 3 al 42%, includendo principalmente anemia (36%) e ipossia (9%). L'azienda ha in programma di avviare PEAK-1, il loro primo studio di Fase 3, nella prima metà del 2025.
Arcus Biosciences presentó datos clínicos prometedores para casdatifan, su inhibidor de HIF-2a, en el tratamiento del cáncer renal metastásico. El estudio de Fase 1/1b (ARC-20) mostró una tasa de respuesta objetiva del 34% (2 respuestas pendientes de confirmación) y una tasa de respuesta confirmada del 25% en la cohorte de expansión de 32 pacientes con dosis diaria de 100 mg. El tratamiento demostró una tasa de control de la enfermedad del 81% con solo un 19% de progresión primaria. El perfil de seguridad fue manejable, con eventos adversos relacionados con el tratamiento de Grado 3 en el 42%, incluyendo principalmente anemia (36%) e hipoxia (9%). La empresa planea iniciar PEAK-1, su primer estudio de Fase 3, en la primera mitad de 2025.
Arcus Biosciences는 전이성 신장암 치료를 위한 HIF-2a 억제제 casdatifan에 대한 유망한 첫 임상 데이터를 발표했습니다. 1/1b상 연구(ARC-20)는 34%의 객관적 반응률(확인 대기 중인 2건의 반응 포함)과 100mg 일일 복용량 확대 집단의 32명 환자에서 25%의 확인된 반응률을 보였습니다. 이 치료는 81%의 질병 조절률을 나타내었으며, 19%의 주요 진행률만 있었습니다. 안전성 프로필은 관리 가능하며, 3등급의 치료 관련 이상 반응은 42%로, 주로 빈혈(36%) 및 저산소증(9%)이 포함되었습니다. 이 회사는 2025년 상반기에 첫 3상 연구인 PEAK-1을 시작할 계획입니다.
Arcus Biosciences a présenté des données cliniques prometteuses pour casdatifan, leur inhibiteur de HIF-2a, dans le traitement du cancer du rein métastatique. L'étude de Phase 1/1b (ARC-20) a montré un taux de réponse objectif de 34% (2 réponses en attente de confirmation) et un taux de réponse confirmé de 25% dans la cohorte d'expansion à une dose quotidienne de 100 mg composée de 32 patients. Le traitement a démontré un taux de contrôle de la maladie de 81% avec seulement 19% de progression primaire. Le profil de sécurité était gérable, avec des événements indésirables liés au traitement de Grade 3 à 42%, comprenant principalement de l'anémie (36%) et de l'hypoxie (9%). La société prévoit de lancer PEAK-1, leur première étude de Phase 3, dans la première moitié de 2025.
Arcus Biosciences hat vielversprechende erste klinische Daten für casdatifan, ihren HIF-2a-Inhibitor, zur Behandlung von fortgeschrittenem Nierenkrebs präsentiert. Die Phase 1/1b-Studie (ARC-20) zeigte eine objektive Ansprechrate von 34% (2 Antworten stehen noch zur Bestätigung aus) und eine bestätigte Ansprechrate von 25% in der 100-mg-Tagesdosis-Erweiterungsgruppe von 32 Patienten. Die Behandlung wies eine Krankheitskontrollrate von 81% auf, bei nur 19% primärer Progression. Das Sicherheitsprofil war handhabbar, mit behandlungsbezogenen unerwünschten Ereignissen der Grad 3 bei 42%, wobei hauptsächlich Anämie (36%) und Hypoxie (9%) betroffen waren. Das Unternehmen plant, PEAK-1, ihre erste Phase-3-Studie, in der ersten Hälfte von 2025 zu starten.
- 34% objective response rate in the 100mg daily dose cohort
- High disease control rate of 81%
- Low primary progression rate of 19%
- Median progression-free survival not yet reached at 11 months follow-up
- No patients discontinued treatment due to anemia
- 42% Grade 3 treatment-emergent adverse events
- 36% of patients experienced anemia as side effect
- 9% of patients experienced hypoxia as side effect
Insights
The initial clinical data for casdatifan shows significant promise in treating metastatic kidney cancer. The 34% objective response rate and 81% disease control rate in heavily pre-treated patients are particularly impressive. Most notable is the low 19% primary progression rate, suggesting strong efficacy in stabilizing disease progression. The drug's safety profile appears manageable, with primarily Grade 3 anemia as the main concern.
The durability of response and median progression-free survival not being reached at 11 months follow-up indicates potential long-term benefits. The planned Phase 3 PEAK-1 study and expansion into first-line treatment could significantly expand the drug's market potential. The combination strategy with cabozantinib and volrustomig shows strategic positioning to compete in both post-PD-1 and first-line settings.
This data represents a significant milestone for Arcus in the $7+ billion kidney cancer market. Casdatifan's potential as a best-in-class HIF-2a inhibitor could capture substantial market share, particularly given the strong efficacy in heavily pre-treated patients. The expansion into first-line treatment and combination therapies positions the drug for broader market opportunities.
The timing of the Phase 3 PEAK-1 study initiation in H1 2025 suggests potential commercialization within 2-3 years, assuming positive results. The collaboration for first-line treatment combinations demonstrates strategic market positioning and could accelerate market penetration upon approval.
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Objective response rate of
34% (2 responses pending confirmation) and25% (confirmed) in the 100mg daily dose expansion cohort (n=32) of ARC-20, a Phase 1/1b study of casdatifan in metastatic clear cell renal cell carcinoma (ccRCC)
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Low rate of primary progression (
19% ) and high rate of disease control (81% ) was observed in the 100mg expansion cohort with many of those patients still on treatment
- Arcus will host a conference call to discuss these results, including results from the 50mg expansion cohort, at 5:00 AM PT / 8:00 AM ET today
“Based on our experience in the ARC-20 study, we have seen casdatifan’s ability to quickly bring tumor growth under control and its high response and disease control rates,” said Toni K. Choueiri, M.D., director of the Lank Center for Genitourinary (GU) Oncology at
“In the 100mg daily dose-expansion cohort of ARC-20, casdatifan showed encouraging results, particularly a low primary progressive disease rate and very durable responses. This was accomplished with a manageable safety profile,” said Dimitry Nuyten, M.D., Ph.D., chief medical officer of Arcus. “These data support the potential for casdatifan to be a best-in-class HIF-2a inhibitor for the treatment of ccRCC. We look forward to initiating our first Phase 3 study for casdatifan, PEAK-1, in the first half of 2025, and expanding our development program into the first-line setting with a novel combination, as well as into other ccRCC subpopulations.”
ARC-20 is a Phase 1/1b dose-escalation and -expansion study. In the dose escalation (20mg to 200mg) portion of the study, the safety profile was comparable across the doses; there were no dose-limiting toxicities, and the maximum tolerated dose was not reached at daily doses of up to 150 mg (200 mg portion of the study is currently ongoing). The 100 mg daily dose (50 mg BID [twice daily]) was selected for dose expansion, and casdatifan was evaluated in patients with metastatic ccRCC who had progressed on at least two prior lines of therapy, including both an anti-PD-1 and a tyrosine kinase inhibitor (TKI) therapy (n=33). The patient population was heavily pre-treated:
At the time of data cut off (DCO, Aug. 30, 2024), median follow-up was 11 months. Casdatifan showed a rapid time to response, and only
Objective Response Rate (ORR) per RECIST v1.1 |
100mg Efficacy-Evaluable* Population (n=32) |
ORR
[ |
[16,50] |
Responses Pending Confirmation |
2** |
Confirmed ORR
[ |
[12,43] |
Progressive Disease |
|
Disease Control Rate
[ |
[64,93] |
Median Progression-Free Survival |
Not Reached |
CI=confidence interval |
|
*100mg daily dose is 50mg BID (twice daily); efficacy-evaluable population for this expansion cohort is defined as all eligible participants who have measurable disease at baseline, receive at least one dose of casdatifan, and have at least one post-baseline efficacy assessment, or who discontinue study treatment due to progressive disease or death. One participant was enrolled but deemed not eligible for the study and was not evaluated for efficacy. |
|
**One patient achieved a response after DCO and nearly a year on treatment, which increased the ORR from |
|
In the 100mg dose-expansion cohort, no unexpected safety signals were observed at the time of DCO, and casdatifan had an acceptable and manageable safety profile. Grade 3 treatment-emergent adverse events (TEAEs) related to casdatifan were
Arcus is pursuing a broad development program in both the first-line and post-anti-PD-1 settings with differentiated combinations to maximize the opportunity for casdatifan in ccRCC. In addition to the monotherapy cohorts of ARC-20, the study is also enrolling a cohort to evaluate casdatifan in combination with cabozantinib, a VEGFR TKI which is intended to support the initiation of Arcus’s planned first Phase 3 study, PEAK-1, evaluating casdatifan in combination with cabozantinib versus cabozantinib monotherapy in patients with metastatic ccRCC who have previously received anti-PD-1 therapy. The primary endpoint will be progression-free survival with a key secondary endpoint of overall survival. Arcus also recently announced a clinical collaboration as part of its first-line strategy in advanced ccRCC to evaluate casdatifan in combination with volrustomig, an investigational anti-PD-1/CTLA-4 bispecific antibody.
Investors may dial in to the conference call at +1 (404) 975- 4839 (local) or +1 (833) 470-1428 (toll-free), using Conference ID: 595409 on Thursday, October 24, 2024 at 5:00 AM PT / 8:00 AM ET. Participants may also register for the call online using the following link: https://www.netroadshow.com/events/login?show=a0338351&confId=70796. In addition to the ARC-20 data, the conference call will address the development strategy and market potential for casdatifan. Arcus will also be joined by Dr. Rana McKay of the University of California San Diego. 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 tumorigenic transcription factor involved in oxygen sensing in multiple organs as well as in tumors. Clear cell RCC is almost universally associated with HIF-2a dysregulation as a result of genetic abnormalities in the VHL pathway. This creates a situation of pseudohypoxia and the abnormal increase in HIF-2a-mediated expression of a broad range of oncogenic proteins. By selectively inhibiting HIF-2a, casdatifan is designed to disable a wide array of pathways involved in tumor proliferation and survival, treatment resistance and angiogenesis, leading to cancer cell death. Casdatifan is being evaluated in ARC-20, a Phase 1/1b study in cancer patients, and STELLAR-009, a Phase 1b/2 study in combination with zanzalintinib in patients with advanced solid tumors, including ccRCC.
Under the Gilead and Arcus collaboration agreement, Gilead has the right to opt-in to development and commercialization for casdatifan after Arcus’s delivery of a qualifying data package.
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’ 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. Nuyten’s and Dr. Choueiri’s quotes and statements regarding: the potency, efficacy or safety of casdatifan, including its potential for a best-in-class profile; casdatifan’s safety profile; ability for casdatifan to be used in first-line therapy; how data from ARC-20 will support or advance Arcus’s development program for casdatifan, including plans for future development; plans to initiate a new Phase 3 study with casdatifan, including timing for initiating any such study; and combinations that Arcus plans to explore in 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 in Arcus’s investigational products; 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:
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VP of Investor Relations & Strategy
(617) 459-2006
peaves@arcusbio.com
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Source: Arcus Biosciences
FAQ
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