First Clinical Data for Arcus Biosciences’ HIF-2a Inhibitor, Casdatifan, Showed Promising Clinical Activity and Tumor Shrinkage in Patients with Metastatic Kidney Cancer
- Objective response rate of 34% (2 responses pending confirmation) and 25% (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)
- 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
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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
“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
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: 52% had received at least three prior lines of therapy; 26% had received at least four prior lines of therapy; and 61% had an
At the time of data cut off (DCO,
|
Objective Response Rate (ORR) per RECIST v1.1 |
100mg Efficacy-Evaluable* Population (n=32) |
|
ORR [95% CI] |
34% (11)** [16,50] |
|
Responses Pending Confirmation |
2** |
|
Confirmed ORR [95% CI] |
25% (8) [12,43] |
|
Progressive Disease |
19% (6) |
|
Disease Control Rate [95% CI] |
81% [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 31% (10) to 34%. |
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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 42%, including anemia (36%) and hypoxia (9%). No patients discontinued treatment from anemia. No TEAEs were life-threatening or led to death.
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
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
About
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
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