Study of ARO-HIF2 in Patients With Advanced Clear Cell Renal Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of ARO-HIF2 injection (also referred to as ARO-HIF2) and to determine the recommended Phase 2 dose in the treatment of patients with advanced clear cell renal cell carcinoma (ccRCC).

Official Title
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A Phase 1b Dose-Finding Study of ARO-HIF2 in Patients With Advanced Clear Cell Renal Cell Carcinoma

Conditions
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Clear Cell Renal Cell Carcinoma

Intervention / Treatment
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* Drug: ARO-HIF2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception Willing to provide written informed consent and to comply with study requirements Histologically confirmed locally advanced or metastatic clear cell renal cell carcinoma that has progressed during or after at least two prior therapeutic regimens which must include vascular endothelial growth factor (VEGF)-targeted therapy and checkpoint inhibitor therapy or that has otherwise failed such therapies, is measurable disease per RECIST 1.1 criteria, is biopsy accessible Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Estimated life expectancy of longer than 3 months Adequate organ function at screening Exclusion Criteria: History of untreated brain metastasis or leptomeningeal disease or spinal cord compression Failure to recover from reversible effects of prior anti-cancer therapy Has received systemic therapy or radiation therapy within 2 weeks prior to first dose History of solid organ or stem cell transplantation Current use of anti-VEGF or mammalian target of rapamycin (mTOR) agents, or chronic immunosuppressive therapy Any prior use of hypoxia inducible factor 2 (HIF2) inhibitors within 6 months prior to first dose Current use of immune checkpoint inhibitors Use of an investigational agent or device within 2 weeks prior to dosing, or current participation in an investigational study Known HIV, hepatitis B or hepatitis C History of other clinically meaningful disease Major surgery within 4 weeks of Screening Active malignancy requiring therapy other than ccRCC within 3 years of study entry Note: Other eligibility criteria may apply per protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARO-HIF2<br> | Drug: ARO-HIF2<br>* Multiple doses of ARO-HIF2 by intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment |  | Up to 2 years from first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of ARO-HIF2: Maximum Observed Plasma Concentration (Cmax) |  | Up to Week 2: predose and up to 48 hours postdose | 
| PK of ARO-HIF2: Time to Maximum Plasma Concentration (Tmax) |  | Up to Week 2: predose and up to 48 hours postdose | 
| PK of ARO-HIF2: Area Under the Plasma Concentration Versus Time Curve from Zero to 4 Hours (AUC0-4) |  | Up to Week 2: predose and up to 48 hours postdose | 
| PK of ARO-HIF2: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24) |  | Up to Week 2: predose and up to 48 hours postdose | 
| PK of ARO-HIF2: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Measurable Concentration at a Time=t, Using a Specified Trapezoidal Rule (AUC0-t) |  | Up to Week 2: predose and up to 48 hours postdose | 
| PK of ARO-HIF2: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf) |  | Up to Week 2: predose and up to 48 hours postdose | 
| PK of ARO-HIF2: Terminal Elimination Half-Life (t1/2) |  | Up to Week 2: predose and up to 48 hours postdose | 
| Systemic Clearance Derived From Intravenous Dose/Area Under the Plasma Concentration Versus Time Curve (CL) |  | Up to Week 2: predose and up to 48 hours postdose | 
| Amount of Drug Excreted in the Urine Over One Dosing Interval Through 4 Hours Post- Dose (Ae, 0-4) |  | Up to Week 2: predose and up to 48 hours postdose | 
| Renal Clearance Calculated by Ae, 0-4 h/AUC0-4h (CLR) |  | Up to Week 2: predose and up to 48 hours postdose | 
| Fraction Excreted (or Equivalently the Percent of Dose Excreted) in the Urine, Calculated by 100 X (Ae, 0-4 h/Dose) |  | Up to Week 2: predose and up to 48 hours postdose | 
| Overall Response Rate | Percentage of participants with a best overall response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 criteria. | Baseline until disease progression, up to 2 years | 
| Duration of Response |  | Baseline until disease progression, up to 2 years | 
| Time to Response |  | Baseline until disease progression, up to 2 years | 
| Progression Free Survival |  | up to 2 years | 
| Overall Survival |  | up to 2 years |