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

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

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).

Study Overview

• Status: Completed
• Conditions: Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: ARO-HIF2

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ARO-HIF2	Drug: ARO-HIF2; Multiple doses of ARO-HIF2 by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
Overall Survival		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
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

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 17, 2020
• Primary Completion (ACTUAL): January 24, 2022
• Study Completion (ACTUAL): July 22, 2022

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (ACTUAL): November 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: AROHIF21001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No