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

Phase 1

Completed

• Conditions: Clear Cell Renal Cell Carcinoma
• Interventions: Drug: ARO-HIF2

• Registration Number: NCT04169711
• Lead Sponsor: Arrowhead Pharmaceuticals

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-11-18
• Study First Submitted QC: 2019-11-18
• Study First Posted: 2019-11-20
• Study Start: 2020-08-17
• Primary Completion: 2022-01-24
• Status Verified: 2022-07
• Study Completion: 2022-07-22
• Last Update Submitted: 2022-07-26
• Last Update Posted: 2022-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ARO-HIF2	ARO-HIF2	-

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment	Up to 2 years from first dose

Secondary Outcome Measures

Name	Time	Method
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: Terminal Elimination Half-Life (t1/2)	Up to Week 2: predose and up to 48 hours postdose
Time to Response	Baseline until disease progression, up to 2 years
Progression Free Survival	up to 2 years
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
Overall Response Rate	Baseline until disease progression, up to 2 years	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.
Duration of Response	Baseline until disease progression, up to 2 years
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
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
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 Survival	up to 2 years
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
Renal Clearance Calculated by Ae, 0-4 h/AUC0-4h (CLR)	Up to Week 2: predose and up to 48 hours postdose

Trial Locations

Locations (1)

Research Site; 🇺🇸 Houston, Texas, United States