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Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer

Primary Purpose

Advanced Solid Tumor, Metastatic Cancer

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AU-007
Aldesleukin
Sponsored by
Aulos Bioscience, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumor focused on measuring IL-2 CD25, IL-2Ra, Clear cell renal cell cancer, Melanoma, Head and neck squamous cell carcinoma, Urothelial cancer, Gastric Cancer, Gastro-esophageal cancer, CD25, IL-2, NSCLC, Bladder Cancer, Merkel Cell Cancer, Proleukin, Immune Therapy, Immunotherapy, Cutaneous Squamous Cell Cancer, Cytokine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Selected Inclusion Criteria:

  • Measurable or non-measurable disease as per RECIST v1.1 criteria and documented by CT and/or MRI.
  • In Dose Escalation patients must have selected tumor types and have progressed after standard of care treatment, or be intolerant to treatment, or refused standard treatment
  • Female patients of childbearing potential must have a negative serum or urine pregnancy test performed within 72 hours prior to the initiation of study drug administration. Female patients of childbearing potential must be willing to use two forms of contraception throughout the study, starting with Screening through 60 days after the last dose of AU-007. Abstinence is acceptable if this is the established and the preferred contraception method for the patient
  • Male patients with partners of childbearing potential must use barrier contraception from the time of consent through 60 days after discontinuation of AU-007 and must not donate sperm during this period. In addition, male patients should have their partners use contraception (as documented for female patients) for the same period of time
  • Patients who have previously received an immune checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have checkpoint inhibitor immune-related toxicity resolved to either Grade ≤ 1 or baseline (prior to the checkpoint inhibitor) to be eligible for enrollment. Patients who experienced previous checkpoint inhibitor-related hypothyroidism are eligible for the study regardless of CTCAE grade resolution if well controlled on thyroid hormone replacement therapy
  • Symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥ 14 days, and meet the following at the time of enrollment:

    • No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids ≥ 10 mg prednisone/day or equivalent)
    • No concurrent leptomeningeal disease or cord compression

Exclusion Criteria:

  • Patients with a history of known autoimmune disease with exceptions of

    • Vitiligo
    • Psoriasis, atopic dermatitis, or other autoimmune skin condition not requiring systemic treatment
    • History of Graves' disease in patients now euthyroid for > 4 weeks
    • Hypothyroidism managed by thyroid hormone replacement
    • Alopecia
    • Arthritis managed without systemic therapy beyond oral nonsteroidal anti- inflammatory drugs
  • Major surgery or traumatic injury within 8 weeks before first dose of AU-007
  • Unhealed wounds from surgery or injury
  • Radiation therapy < 2 weeks prior to initiation of AU-007
  • Treatment with > 10 mg per day of prednisone (or equivalent) or other immune-suppressive drugs within the 7 days prior to the initiation of study drug. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed
  • Prior therapy within the following timeframe before the planned start of AU-007 as follows:

    • Cytotoxic chemotherapy, small molecule inhibitors, radiation, interventional radiology procedure, or similar investigational therapies: ≤ 2 weeks or 5 half-lives, whichever is shorter
    • Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar investigational therapies: ≤ 4 weeks
    • Concurrent use of hormones either to maintain castrate levels of testosterone in patients with castration-sensitive prostate cancer or for non-cancer-related conditions (e.g., insulin for diabetes, hormone replacement therapy) is acceptable. Bisphosphonates are permitted
  • Inflammatory process that has not resolved for ≥ 4 weeks from the date of first study dose. Patients with chronic low-grade inflammatory processes such as radiation-induced pneumonitis are excluded regardless of duration
  • Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions include non-melanoma locally advanced skin cancer, cervical carcinoma in situ, localized prostate cancer (Gleason score ≤ 7), resected melanoma in situ, or any malignancy considered to be indolent and never required therapy, with the exception of indolent lymphomas

Sites / Locations

  • Carolina Biooncology InstituteRecruiting
  • Tennessee OncologyRecruiting
  • MD Anderson Cancer Center
  • START South Texas Accelerated Research TherapeuticsRecruiting
  • Southside Cancer Care CentreRecruiting
  • Monash HealthRecruiting
  • Austin HealthRecruiting
  • The Alfred HospitalRecruiting
  • Sunshine Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

AU-007 Monotherapy

AU-007 combined with an aldesleukin loading dose

AU-007 combined with aldesleukin given concomitantly

Arm Description

AU-007 (Q2w) will be administered as a monotherapy sequential ascending doses with each Dose Escalation Cohort

AU-007 (Q2w) will be administered at a fixed dose in combination with a single dose of aldesleukin with the initial AU-007 dose. The aldesleukin dose will be escalated with each Dose Escalation Cohort

AU-007 will be administered at a fixed dose in combination with a aldesleukin, both administered Q2w. The aldesleukin dose will be escalated with each Dose Escalation Cohort

Outcomes

Primary Outcome Measures

Evaluate the safety and tolerability of AU-007
Measured by the frequency of DLTs (Dose limiting Toxicity) and safety profile
Establish the maximum tolerated dose (MTD) and or/ recommended Phase 2 dose (RP2D)
With AU-007 alone or in combination with aldesleukin measured by PK, PD, and Biomarkers

Secondary Outcome Measures

Magnitude of Pharmacokinetic changes in the blood after dosing determined by area under the curve (AUC) of AU-007
The AUC of AU-007 will be measured at different timepoints after AU-007 administration
Magnitude of Pharmacokinetic changes in the blood after dosing determined by maximum concentration (Cmax) of AU-007
The Cmax of AU-007 will be measured at different timepoints after AU-007 administration
Magnitude of Pharmacokinetic changes in the blood after dosing determined by time of maximum concentration (Tmax)
The Tmax of AU-007 will be measured at different timepoints after AU-007 administration
Magnitude of Pharmacokinetic changes in the blood after dosing determined by Half-life (T1/2) of AU-007
The T1/2 of AU-007 will be measured at different timepoints after AU-007 administration
Magnitude of cytokine changes in the blood after dosing
Magnitude of immunogenicity after dosing with AU-007 alone or in combination with aldesleukin
Assessed by summarizing the number of patients who develop detectable anti-drug antibodies (ADAs) at different timepoints after AU-007 alone or in combination with aldesleukin
Evaluate the preliminary anti-tumor activity of AU-007 alone or in combination with aldesleukin in patients with unresectable locally advanced or metastatic cancer
Clinical anti-tumor activity will be evaluated using conventional Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and modified RECIST v1.1.

Full Information

First Posted
February 10, 2022
Last Updated
August 28, 2023
Sponsor
Aulos Bioscience, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05267626
Brief Title
Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer
Official Title
A Phase 1/2, First-in-Human, Open Label, Dose Escalation and Expansion Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 4, 2022 (Actual)
Primary Completion Date
July 30, 2024 (Anticipated)
Study Completion Date
October 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aulos Bioscience, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a first in human, open-label, multi-center Phase 1 / 2 study to evaluate the safety, tolerability, and initial efficacy of AU-007 in patients with advanced solid tumors. AU-007 will be administered either as a monotherapy, or in combination with a single loading dose of aldesleukin, or with both AU-007 and aldesleukin given every 2 weeks (Q2w)
Detailed Description
This is a first in human, multicenter, open-label Phase 1-2 study evaluating the safety, tolerability, and initial efficacy of AU-007 with or without aldesleukin, in patients with unresectable locally advanced or metastatic cancer. Patients must either be ineligible for or have progressed on prior standard of care therapy. Phase 1 consists of 3 escalation Arms, each starting with a single 1+2 escalation cohort followed by 3+3 escalation cohorts to define the recommended Phase 2 dose (RP2D) or maximum tolerated dose (MTD). The study begins in Arm A evaluating escalating doses of AU-007 (Q2w) in sequential escalation cohorts to define the recommended Phase 2 dose (RP2D) or maximum tolerated dose (MTD). In Arm B, AU-007 (Q2w) is evaluated in combination with a single dose of aldesleukin given with the first AU-007 dose. AU-007 is administered at a fixed dose (Q2w) with an escalating single aldesleukin dose in sequential escalation cohorts. In Arm C, AU-007 is evaluated in combination with aldesleukin both given Q2w. AU-007 will be administered at a fixed dose with an escalating dose of aldesleukin in each sequential Arm C escalation cohort. The Phase 2, cohort expansion portion of the study consists of three expansion Arms evaluating the initial efficacy of the RP2D from corresponding dose escalation Arms A, B, and C in selected solid tumor types. Initially, melanoma and renal cell cancer will be evaluated in each Arm. Other eligible cancers include but not limited to Merkel Cell Carcinoma, non-small cell lung cancer and urothelial cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumor, Metastatic Cancer
Keywords
IL-2 CD25, IL-2Ra, Clear cell renal cell cancer, Melanoma, Head and neck squamous cell carcinoma, Urothelial cancer, Gastric Cancer, Gastro-esophageal cancer, CD25, IL-2, NSCLC, Bladder Cancer, Merkel Cell Cancer, Proleukin, Immune Therapy, Immunotherapy, Cutaneous Squamous Cell Cancer, Cytokine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
69 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AU-007 Monotherapy
Arm Type
Experimental
Arm Description
AU-007 (Q2w) will be administered as a monotherapy sequential ascending doses with each Dose Escalation Cohort
Arm Title
AU-007 combined with an aldesleukin loading dose
Arm Type
Experimental
Arm Description
AU-007 (Q2w) will be administered at a fixed dose in combination with a single dose of aldesleukin with the initial AU-007 dose. The aldesleukin dose will be escalated with each Dose Escalation Cohort
Arm Title
AU-007 combined with aldesleukin given concomitantly
Arm Type
Experimental
Arm Description
AU-007 will be administered at a fixed dose in combination with a aldesleukin, both administered Q2w. The aldesleukin dose will be escalated with each Dose Escalation Cohort
Intervention Type
Drug
Intervention Name(s)
AU-007
Intervention Description
Monoclonal Antibody Targeting IL-2
Intervention Type
Drug
Intervention Name(s)
Aldesleukin
Intervention Description
IL-2
Primary Outcome Measure Information:
Title
Evaluate the safety and tolerability of AU-007
Description
Measured by the frequency of DLTs (Dose limiting Toxicity) and safety profile
Time Frame
Day 1 thru EOT visit (28 days after last dose)
Title
Establish the maximum tolerated dose (MTD) and or/ recommended Phase 2 dose (RP2D)
Description
With AU-007 alone or in combination with aldesleukin measured by PK, PD, and Biomarkers
Time Frame
Day 1 thru EOT visit (28 days after last dose)
Secondary Outcome Measure Information:
Title
Magnitude of Pharmacokinetic changes in the blood after dosing determined by area under the curve (AUC) of AU-007
Description
The AUC of AU-007 will be measured at different timepoints after AU-007 administration
Time Frame
Day 1 thru EOT visit (28 days after last dose)
Title
Magnitude of Pharmacokinetic changes in the blood after dosing determined by maximum concentration (Cmax) of AU-007
Description
The Cmax of AU-007 will be measured at different timepoints after AU-007 administration
Time Frame
Day 1 thru EOT visit (28 days after last dose)
Title
Magnitude of Pharmacokinetic changes in the blood after dosing determined by time of maximum concentration (Tmax)
Description
The Tmax of AU-007 will be measured at different timepoints after AU-007 administration
Time Frame
Day 1 thru EOT visit (28 days after last dose)
Title
Magnitude of Pharmacokinetic changes in the blood after dosing determined by Half-life (T1/2) of AU-007
Description
The T1/2 of AU-007 will be measured at different timepoints after AU-007 administration
Time Frame
Day 1 thru EOT visit (28 days after last dose)
Title
Magnitude of cytokine changes in the blood after dosing
Time Frame
Day 1 thru EOT visit (28 days after last dose)
Title
Magnitude of immunogenicity after dosing with AU-007 alone or in combination with aldesleukin
Description
Assessed by summarizing the number of patients who develop detectable anti-drug antibodies (ADAs) at different timepoints after AU-007 alone or in combination with aldesleukin
Time Frame
Day 1 thru EOT visit (28 days after last dose)
Title
Evaluate the preliminary anti-tumor activity of AU-007 alone or in combination with aldesleukin in patients with unresectable locally advanced or metastatic cancer
Description
Clinical anti-tumor activity will be evaluated using conventional Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and modified RECIST v1.1.
Time Frame
Day 1 thru EOT visit (28 days after last dose)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Selected Inclusion Criteria: Measurable or non-measurable disease as per RECIST v1.1 criteria and documented by CT and/or MRI. In Cohort Expansion, patients with truly non-measurable only disease (e.g., ascites, pleural or pericardial effusion, organomegaly), are not eligible for enrolment. In Dose Escalation patients must have selected tumor types and have progressed after standard of care treatment, or be intolerant to treatment, or refused standard treatment Female patients of childbearing potential must have a negative serum or urine pregnancy test performed within 72 hours prior to the initiation of study drug administration. Female patients of childbearing potential must be willing to use two forms of contraception throughout the study, starting with Screening through 60 days after the last dose of AU-007. Abstinence is acceptable if this is the established and the preferred contraception method for the patient Male patients with partners of childbearing potential must use barrier contraception from the time of consent through 60 days after discontinuation of AU-007 and must not donate sperm during this period. In addition, male patients should have their partners use contraception (as documented for female patients) for the same period of time Patients who have previously received an immune checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have checkpoint inhibitor immune-related toxicity resolved to either Grade ≤ 1 or baseline (prior to the checkpoint inhibitor) to be eligible for enrollment. Patients who experienced previous checkpoint inhibitor-related hypothyroidism are eligible for the study regardless of CTCAE grade resolution if well controlled on thyroid hormone replacement therapy Symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥ 14 days, and meet the following at the time of enrollment: No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids ≥ 10 mg prednisone/day or equivalent) No concurrent leptomeningeal disease or cord compression Exclusion Criteria: Patients with a history of known autoimmune disease with exceptions of Vitiligo Psoriasis, atopic dermatitis, or other autoimmune skin condition not requiring systemic treatment History of Graves' disease in patients now euthyroid for > 4 weeks Hypothyroidism managed by thyroid hormone replacement Alopecia Arthritis managed without systemic therapy beyond oral nonsteroidal anti- inflammatory drugs Major surgery or traumatic injury within 8 weeks before first dose of AU-007 Unhealed wounds from surgery or injury Treatment with > 10 mg per day of prednisone (or equivalent) or other immune-suppressive drugs within the 7 days prior to the initiation of study drug. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed Prior anti-cancer therapy before the planned start of AU-007 as follows: Not recovered to baseline from toxicity of prior systemic cancer therapy(ies). Not recovered from toxicity of radiotherapy. Concurrent use of hormones either to maintain castrate levels of testosterone in patients with castration-sensitive prostate cancer or for non-cancer-related conditions (e.g., insulin for diabetes, hormone replacement therapy) is acceptable. Bisphosphonates are permitted. Patients who have experienced SAEs during prior IL-2 therapy (including but not limited to bowel perforation, GI bleeding, arrythmias, MI, repetitive seizures). Inflammatory process that has not resolved for ≥ 4 weeks from the date of first study dose. Patients with chronic low-grade inflammatory processes such as radiation-induced pneumonitis are excluded regardless of duration Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions include non-melanoma locally advanced skin cancer, cervical carcinoma in situ, localized prostate cancer (Gleason score ≤ 7), resected melanoma in situ, or any malignancy considered to be indolent and never required therapy, with the exception of indolent lymphomas
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Vasselli, MD
Organizational Affiliation
Aulos Bioscience, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Carolina Biooncology Institute
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Powderly, MD
Phone
704-947-6599
Email
jpowderly@carolinabiooncology.org
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203-1619
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meredith McKean
Phone
615-329-7274
Email
mmckean@tnonc.com
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4000
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
George Blumenschein
Phone
713-792-6363
Email
gblumens@mdanderson.org
Facility Name
START South Texas Accelerated Research Therapeutics
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Drew Rasco
Phone
210-593-5265
Email
drew.rasco@startsa.com
Facility Name
Southside Cancer Care Centre
City
Miranda
State/Province
New South Wales
ZIP/Postal Code
2228
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul DeSouza
Phone
+61(02) 95539588
Email
P.DeSouza@westernsydney.edu.au
Facility Name
Monash Health
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Ahern
Phone
+61(03) 8572 2392
Email
Elizabeth.Ahern@monashhealth.org
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Weickhardt
Phone
+61(03) 9496 9918
Email
Andrew.WEICKHARDT@austin.org.au
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Haydon, MD
Phone
+61390766963
Email
andrew.haydon@monash.edu
Facility Name
Sunshine Hospital
City
Saint Albans
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Oakman
Phone
+61383456666
Email
catherine.oakman@wh.org.au

12. IPD Sharing Statement

Learn more about this trial

Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer

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