Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05267626




Registration number
NCT05267626
Ethics application status
Date submitted
10/02/2022
Date registered
4/03/2022
Date last updated
24/10/2024

Titles & IDs
Public title
Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Ra Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer
Scientific 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-2Ra Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer
Secondary ID [1] 0 0
CP-AU-007-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Metastatic Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AU-007
Treatment: Drugs - Aldesleukin
Treatment: Drugs - Avelumab

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

Experimental: AU-007 combined with an aldesleukin loading dose - AU-007 (Q2w) will be administered in combination with a single dose of aldesleukin with the initial AU-007 dose.

Experimental: AU-007 combined with aldesleukin given concomitantly - AU-007 will be administered in combination with aldesleukin, both administered Q2w.

Experimental: AU-007 combined with aldesleukin and avelumab given concomitantly - AU-007 and avelumab will be administered Q2w, with either a single loading dose or Q2w aldesleukin.


Treatment: Drugs: AU-007
Monoclonal Antibody Targeting IL-2

Treatment: Drugs: Aldesleukin
IL-2

Treatment: Drugs: Avelumab
Monoclonal Antibody Targeting PD-L1
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Evaluate the safety and tolerability of AU-007
Timepoint [1] 0 0
Day 1 thru end of treatment (EOT) visit (28 days after last dose)
Primary outcome [2] 0 0
Establish the maximum tolerated dose (MTD) and/or RP2D
Timepoint [2] 0 0
Day 1 thru EOT visit (28 days after last dose)
Secondary outcome [1] 0 0
Magnitude of PK changes in the blood after dosing determined by area under the curve (AUC) of AU-007
Timepoint [1] 0 0
Day 1 thru EOT visit (28 days after last dose)
Secondary outcome [2] 0 0
Magnitude of PK changes in the blood after dosing determined by maximum concentration (Cmax) of AU-007
Timepoint [2] 0 0
Day 1 thru EOT visit (28 days after last dose)
Secondary outcome [3] 0 0
Magnitude of PK changes in the blood after dosing determined by time of maximum concentration (Tmax)
Timepoint [3] 0 0
Day 1 thru EOT visit (28 days after last dose)
Secondary outcome [4] 0 0
Magnitude of PK changes in the blood after dosing determined by Half-life (T1/2) of AU-007
Timepoint [4] 0 0
Day 1 thru EOT visit (28 days after last dose)
Secondary outcome [5] 0 0
Magnitude of cytokine changes in the blood after dosing
Timepoint [5] 0 0
Day 1 thru EOT visit (28 days after last dose)
Secondary outcome [6] 0 0
Magnitude of immunogenicity after dosing with AU-007 alone or in combination with aldesleukin
Timepoint [6] 0 0
Day 1 thru EOT visit (28 days after last dose)
Secondary outcome [7] 0 0
Evaluate the preliminary anti-tumor activity of AU-007 alone, in combination with aldesleukin, and in combination with aldesleukin and avelumab in patients with unresectable locally advanced or metastatic cancer
Timepoint [7] 0 0
Day 1 thru EOT visit (28 days after last dose)

Eligibility
Key inclusion criteria
Selected

* 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 enrollment
* 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
* Part 2 includes but is not limited to:
* Renal cell cancer progressing during or following at least two approved therapeutic regimens (e.g., small molecule inhibitors, anti-PDx therapy)
* Cutaneous melanoma that is either locally unresectable or metastatic:

* BRAF wild type: progressed after receiving PD-1 containing therapy with or without an anti-CTLA-4
* BRAF mutation: patients who refused BRAF+MEK inhibitor
* NSCLC: Unresectable locally advanced or metastatic PD-L1-positive (= 1%) NSCLC not harboring an activating EGFR mutation or ALK rearrangement and has progressed during or following treatment with an anti-PDx and platinum-based chemotherapy (unless ineligible for platinum therapy)
* Part 3: NSCLC as described above
* 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 study drug. 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 study drug 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 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 serious adverse events during prior IL-2 therapy (including but not limited to bowel perforation, gastrointestinal bleeding, arrythmias, myocardial infarction, 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2025
Actual
Sample size
Target
159
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Southside Cancer Care Centre - Miranda
Recruitment hospital [2] 0 0
Southern Oncology Clinical Research Unit - Bedford Park
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [5] 0 0
Austin Health - Heidelberg
Recruitment hospital [6] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [7] 0 0
Sunshine Hospital - Saint Albans
Recruitment postcode(s) [1] 0 0
2228 - Miranda
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment postcode(s) [7] 0 0
3021 - Saint Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Michigan
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
United States of America
State/province [5] 0 0
Utah

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Aulos Bioscience, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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). Once the recommended phase 2 dose (RP2D) of AU-007 plus aldesleukin is determined, AU-007 plus aldesleukin will also be administered with avelumab.
Trial website
https://clinicaltrials.gov/study/NCT05267626
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James Vasselli, MD
Address 0 0
Aulos Bioscience, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Senior Clinical Trial Manager
Address 0 0
Country 0 0
Phone 0 0
(707) 758-6776
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05267626