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Trial registered on ANZCTR


Registration number
ACTRN12617001641381
Ethics application status
Approved
Date submitted
10/11/2017
Date registered
18/12/2017
Date last updated
8/06/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1 Study to Evaluate the Safety and Tolerability of AB122 in Subjects with Advanced Solid Tumors
Scientific title
A Phase 1 Study to Evaluate the Safety and Tolerability of AB122 in Subjects with Advanced Solid Tumors
Secondary ID [1] 293122 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 305112 0
Endometrial cancer 305508 0
Merkel cell carcinoma 305509 0
Condition category
Condition code
Cancer 304424 304424 0 0
Lung - Non small cell
Cancer 304425 304425 0 0
Head and neck
Cancer 304426 304426 0 0
Kidney
Cancer 304427 304427 0 0
Breast
Cancer 304428 304428 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 304429 304429 0 0
Prostate
Cancer 304432 304432 0 0
Bladder
Cancer 304433 304433 0 0
Ovarian and primary peritoneal
Cancer 304434 304434 0 0
Oesophageal (gullet)
Cancer 304668 304668 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study drug: AB122 solution for infusion.

This is a dose escalation study with up to 36 subjects testing safety, pharmacokinetics and pharmacodynamics.

The study will consist of two parts, Part 1 and Part 2.

In Part 1 three cohorts will be dosed 80, 240 and 720mg of AB122 respectively. Subjects will initially be assigned to the Q2W dosing schedule(every 2 weeks). The Q3W dosing schedule (every 3 weeks) will be considered if de-escalation is required.

Part 2 will confirm Pharacokinetic and Pharmacodynamics from Part 1. Dosing will either occur every 2, 3 or 4 weeks (Q2W, Q3W or Q4W respectively) there by subjects will be administered 2 doses of study drug per cycle for the Q2W schedule and one dose of study drug per cycle for the Q3W and Q4W schedules.

Cycles for Q2W and Q4W dosing are 28 days, and Q3W dosing Cycle is 21 days. Overall duration of treatment will depend on how well the treatment is tolerated. Treatment may continue until unacceptable toxicity or progressive disease or other reasons specified in the protocol.
Intervention code [1] 299391 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 303661 0
To evaluate the safety and tolerability of AB122 in subjects with advanced solid tumors.

The Incidence of adverse events (AEs) and dose-limiting toxicities (DLTs) will be measured by clinical examination.
Timepoint [1] 303661 0
Recorded at baseline (screening), on days 1, 2, 3, 8, 15 and then every 2 weeks on treatment, at end of treatment and every 30 days until 6 months post dose (i.e. at 30, 60 and 90 days, and 6 months) for Q2W and Q4W dosing schedules.

Recorded at baseline (screening), on days 1, 2, 3, 8, 22 and then every 3 weeks on treatment, at end of treatment and every 30 days until 6 months post dose (i.e. at 30, 60 and 90 days, and 6 months) for Q3W dosing schedule.
Primary outcome [2] 303980 0
To evaluate the safety and tolerability of AB122 in subjects with advanced solid tumors.

Safety and clinical laboratory parameters (biochemistry, hematology and urinalysis) will be measured by blood and urine analysis.
Timepoint [2] 303980 0
Recorded at baseline (screening), on days 1, 2, 3, 8, 15 and then every 2 weeks on treatment, at end of treatment and every 30 days until 6 months post dose (i.e. at 30, 60 and 90 days, and 6 months) for Q2W and Q4W dosing schedules.

Recorded at baseline (screening), on days 1, 2, 3, 8, 22 and then every 3 weeks on treatment, at end of treatment and every 30 days until 6 months post dose (i.e. at 30, 60 and 90 days, and 6 months) for Q3W dosing schedule.
Secondary outcome [1] 339807 0
To describe the immunogenicity of AB122 in subjects with advanced solid tumors by serum analysis.
Timepoint [1] 339807 0
Immunogenity is collected pre-dose only on days when it coincides with a treatment day.

Recorded on days 1, 15, 29, 43 and 85 of treatment, at end of treatment, 90 days post last dose and 6 months from end of treatment for Q2W dosing schedule.

Recorded on days 1, 22 and 64 of treatment, at end of treatment, 90 days post last dose and 6 months from end of treatment for Q3W dosing schedule.

Recorded on days 1, 29 and 85 of treatment, and end of treatment, 90 days post last dose and 6 months from end of treatment for Q4W dosing schedule.
Secondary outcome [2] 339808 0
To describe the pharmacokinetics (PK) of AB122 in subjects with advanced solid tumors. Serum samples will be collected for PK analysis to record AB122 serum concentration and PK parameters.

PK parameters to be assessed:
-Area under the concentration-time curve
-Maximum concentration of AB122
-Time to maximum concentration
Timepoint [2] 339808 0
Recorded on days 1 (pre- and 1hr post-dose), 2 (24hrs post-dose), 3 (48hrs post-dose), 8 (168hrs post-dose), 15 (pre-dose), 29 (pre- and 1hr post-dose), 43 (pre-dose), 57 (pre-dose) and 85 (pre-dose) of treatment, at end of treatment and 90 days post last dose for Q2W and Q4W dosing schedules.

Recorded on days 1 (pre- and 1hr post-dose), 2 (24hrs post-dose), 3 (48hrs post-dose), 8 (168hrs post-dose), 22 (pre- and 1hr post-dose), 43 (pre- and 1hr post-dose) and 64 (pre- and 1hr post-dose) of treatment, at end of treatment and 90 days post last dose for Q3W dosing schedule.
Secondary outcome [3] 339817 0
To assess the potential pharmacodynamic (PD) activity of AB122 in subjects with advanced solid tumors. Whole blood samples will be collected for PD analysis to record receptor occupancy of AB122 in peripheral blood and immunomodulatory activity of AB122 in select immune subsets which is a composite assessment.
Timepoint [3] 339817 0
Recorded on days 1 (pre- and 1hr post-dose), 2 (24hrs post-dose), 15 (pre-dose), 29 (pre-dose), 57 (pre-dose) and 85 (pre-dose) of treatment, at end of treatment and 90 days post last dose for Q2W dosing schedule.

Recorded on days 1 (pre- and 1hr post-dose), 2 (24hrs post-dose), 22 (pre-dose), 43 (pre-dose) and 64 (pre-dose) of treatment, at end of treatment and 90 days post last dose for Q3W dosing schedule.

Recorded on days 1 (pre- and 1hr post-dose), 2 (24hrs post-dose), 29 (pre-dose), 57 (pre-dose) and 85 (pre-dose) of treatment, at end of treatment and 90 days post last dose for Q4W dosing schedule.
Secondary outcome [4] 339818 0
To determine the clinical activity of AB122 in subjects with advanced solid tumors.
Timepoint [4] 339818 0
The composite assessment including Objective response rate (ORR), Disease control rate (DCR), Duration of response (DoR), Progression-free survival (FPS) based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 is recorded at baseline (screening), on days 57 and 113 of treatment and 8 weeks from end of treatment for Q2W and Q4W dosing schedules or at baseline (screening), on day 64 of treatment and 8 weeks from end of treatment for Q3W dosing schedule.


Eligibility
Key inclusion criteria
1. Male or Female adults (18 years or over)

2. Pathologically confirmed non-small-cell lung cancer, squamous cell carcinoma of the head and neck, renal cell carcinoma, breast cancer, colorectal cancer (CRC), prostate cancer, melanoma, bladder cancer, ovarian cancer, endometrial cancer, Merkel cell carcinoma, or gastroesophageal cancer that is metastatic, advanced or recurrent with progression for which no alternative or curative therapy exists or standard therapy is not considered appropriate by the subject and treating physician.

3. ECOG performance status of 0 or 1.

4. Must have at least 1 measurable lesion per RECIST. Subjects with prostate cancer who have bone-only lesions must have progression of 2 lesions or a new lesion and rising prostate-specific antigen levels. The measurable lesion must be outside of a radiation field if the subject received prior radiation.

5. Up to 5 lines of prior systemic therapies for advanced/recurrent and progressing disease (an unlimited number of prior hormonal therapies is allowed).

6. Adequate organ and marrow function.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior treatment with an anti-PD-L1, anti-PD-1, anti-CTLA-4, or other immune checkpoint inhibitor or agonist as monotherapy or in combination.

2. Has had prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 2 weeks prior to Day 1 or has not recovered from AEs due to a previously administered agent.

3. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration.

4. Use of any vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of study therapy.

5. Any active autoimmune disease or a documented history of autoimmune disease, or history of a syndrome that required systemic steroids or immunosuppressive medications, except for vitiligo or resolved childhood asthma/atopy. Subjects with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.

6. Any acute gastrointestinal symptoms (eg, nausea, vomiting, diarrhea, heartburn) at the time of screening or admission.

7. Underlying medical conditions that, in the investigator’s opinion, will make the administration of study drug hazardous (ie, interstitial lung disease, active infections requiring antibiotics, recent hospitalization with unresolved symptoms, etc) or obscure the interpretation of toxicity determination or AEs or concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids.

8. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

9. Prior malignancy active within the previous year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.

10. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment

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 design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9189 0
St George Private Hospital - Kogarah
Recruitment hospital [2] 11109 0
Sydney Southwest Private Hospital - Liverpool
Recruitment postcode(s) [1] 17842 0
2217 - Kogarah
Recruitment postcode(s) [2] 22922 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 297748 0
Commercial sector/Industry
Name [1] 297748 0
Arcus Biosciences, Inc.
Address [1] 297748 0
3928 Point Eden Way
Hayward, CA 94545
Country [1] 297748 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Arcus Biosciences, Inc.
Address
3928 Point Eden Way
Hayward, CA 94545
Country
United States of America
Secondary sponsor category [1] 296805 0
Commercial sector/Industry
Name [1] 296805 0
Arcus Biosciences Australia Pty Ltd.
Address [1] 296805 0
Floor 4, 34 Queen St.
Melbourne, VIC 3000
Country [1] 296805 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298811 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 298811 0
129 Glen Osmond Road
Eastwood South Australia 5063
Ethics committee country [1] 298811 0
Australia
Date submitted for ethics approval [1] 298811 0
04/10/2017
Approval date [1] 298811 0
30/10/2017
Ethics approval number [1] 298811 0
2017-10-748

Summary
Brief summary
This research study is testing the safety and tolerability of a potential new drug called AB122 in subjects with advanced solid tumours.

Who is it for?
You may be eligible to join this study if you are aged 18 years or over and have a pathologically confirmed solid cancer that is metastatic, advanced or recurrent with progression for which no alternative or curative therapy exists or standard therapy is not considered appropriate by the subject and treating physician.

Study details
A major purpose of this study is to find a safe dose range of AB122 that can be given to humans with cancer. To do this, multiple study cohorts will be enrolled and receive ascending doses of AB122. This means that if one dose has passed the safety and tolerability review, the next higher dose will be given to the subsequent patient cohort. The study will stop once the maximum tolerable dose is determined. In addition, the study will look at the amount of study drug in the blood to evaluate the way the body processes the study drug (pharmacokinetics) and the way the study drug affects the growth of tumours in cancer patients (pharmacodynamics).

This research study will help us understand whether AB122, the study drug, can be safely given to patients with cancer.
Trial website
NA
Trial related presentations / publications
NA
Public notes
NA

Contacts
Principal investigator
Name 78302 0
Prof Paul de Souza
Address 78302 0
Suite 5, Level 4,
St George Private Hospital,
1 South Street,
Kogarah, NSW, 2217
Country 78302 0
Australia
Phone 78302 0
+61 2 9553 9588
Fax 78302 0
+61 2 9553 7805
Email 78302 0
p.desouza@unsw.edu.au
Contact person for public queries
Name 78303 0
Dr Joyson Karakunnel
Address 78303 0
Arcus Biosciences, Inc.
3928 Point Eden Way
Hayward, CA 94545
Country 78303 0
United States of America
Phone 78303 0
+1 510 694 6267
Fax 78303 0
Email 78303 0
ClinicalTrialInquiry@arcusbio.com
Contact person for scientific queries
Name 78304 0
Dr Joyson Karakunnel
Address 78304 0
Arcus Biosciences, Inc.
3928 Point Eden Way
Hayward, CA 94545
Country 78304 0
United States of America
Phone 78304 0
+1 510 694 6267
Fax 78304 0
Email 78304 0
ClinicalTrialInquiry@arcusbio.com

No data has been provided for results reporting
Summary results
Not applicable