Trial Review

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/ct2/show/NCT03628677




Registration number
NCT03628677
Ethics application status
Date submitted
26/07/2018
Date registered
14/08/2018
Date last updated
24/05/2024

Titles & IDs
Public title
A Study to Evaluate the Safety and Tolerability of AB154 in Participants With Advanced Malignancies
Scientific title
A Phase 1 Study to Evaluate the Safety and Tolerability of AB154 Monotherapy and Combination Therapy in Participants With Advanced Malignancies
Secondary ID [1] 0 0
AB154CSP0001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor, Unspecified, Adult 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Domvanalimab
Treatment: Drugs - Zimberelimab

Experimental: Domvanalimab Monotherapy - Varying Doses of domvanalimab Monotherapy

Experimental: Domvanalimab + zimberelimab Q2W Combination Therapy - Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Experimental: Domvanalimab + zimberelimab Q3W Combination Therapy - Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Experimental: Domvanalimab + zimberelimab Q4W Combination Therapy - Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Experimental: Domvanalimab and Zimberelimab Q6W combination therapy - Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Experimental: Fixed dose Domvanalimab Q3W or Q4W and Zimberelimab Q3W, Q4W - Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab


Treatment: Drugs: Domvanalimab
Domvanalimabis a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT

Treatment: Drugs: Zimberelimab
Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
Timepoint [1] 0 0
From First Dose Date to 100 Days After Last Dose
Secondary outcome [1] 0 0
AB154 Peak Plasma Concentration (Cmax)
Timepoint [1] 0 0
Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary outcome [2] 0 0
Zimberelimab Peak Plasma Concentration (Cmax)
Timepoint [2] 0 0
Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary outcome [3] 0 0
Domvanalimab Time of Peak Concentration (Tmax)
Timepoint [3] 0 0
Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary outcome [4] 0 0
Zimberelimab Time of Peak Concentration (Tmax)
Timepoint [4] 0 0
Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary outcome [5] 0 0
Domvanalimab Area Under the Plasma Concentration Versus Time Curve (AUC)
Timepoint [5] 0 0
Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary outcome [6] 0 0
Zimberelimab Area Under the Plasma Concentration Versus Time Curve (AUC)
Timepoint [6] 0 0
Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary outcome [7] 0 0
Immunogenicity Indicators: Anti-Drug Antibodies (ADA)
Timepoint [7] 0 0
Day 1, Day 15, Day 29, Day 43, Day 57, Day 85 and 30 Days After Last Dose, up to 52 weeks
Secondary outcome [8] 0 0
Overall Response Rate
Timepoint [8] 0 0
First Dose Date to Progression or Last Tumor Assessment, up to 1 year
Secondary outcome [9] 0 0
Duration of Response
Timepoint [9] 0 0
Start Date of Response to First Progression/Death, up to 1 year
Secondary outcome [10] 0 0
Disease Control Rate
Timepoint [10] 0 0
First Dose Date to First Progression/Death, up to 1 year
Secondary outcome [11] 0 0
Progression Free Survival
Timepoint [11] 0 0
First Dose Date to First Progression/Death, up to 1 year
Secondary outcome [12] 0 0
Overall Survival
Timepoint [12] 0 0
First Dose Date to Date of Death, up to 1 year

Eligibility
Key inclusion criteria
- Capable of giving signed informed consent

- Male or female participants = 18 years of age at the time of screening

- Negative serum pregnancy test at screening and prior to dosing on Cycle 1 Day 1;
negative serum or urine pregnancy test on the first day of each subsequent treatment
period

- Participants with any pathologically confirmed solid tumor type for which no standard
of care therapy exists

- Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1. The measurable lesion must be outside of a radiation field if
the participant received prior radiation

- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 7.
Confirmation that an archival tissue sample is available and = 6 months old; if not, a
new biopsy of a tumor must be obtained 8. Immunosuppressive doses of systemic
medications, such as corticosteroids or absorbed topical corticosteroids (doses > 10
mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days)
before investigational product administration. Physiologic doses of corticosteroids =
10 mg/day of prednisone or its equivalent may be permitted

- Prior surgery that required general anesthesia or other major surgery as defined by
the Investigator must be completed at least 4 weeks before investigational product
administration

- Negative tests for hepatitis B surface antigen, hepatitis C virus antibody (or
hepatitis C qualitative ribonucleic acid [RNA; qualitative]), and human
immunodeficiency virus (HIV)-1 and HIV-2 antibody at screening

- Adequate organ and marrow function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Use of any live vaccines against infectious diseases (eg, influenza, varicella) within
4 weeks (28 days) of initiation of investigational product

- Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will
make the administration of investigational product hazardous (eg, interstitial lung
disease, active infections requiring antibiotics, recent hospitalization with
unresolved symptoms)

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

- 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 100 days after the last dose of domvanalimab as monotherapy and in combination
with zimberelimab.

- Participants who require a Legally Authorized Representative (LAR) to provide informed
consent on their behalf.

- 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. Participants with asthma who require
intermittent use of bronchodilators (such as albuterol) will not be excluded from this
study

- 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, breast, or prostate
cancer

- Has had prior chemotherapy, targeted small-molecule therapy, immunotherapy (tumor
vaccine, cytokine, or growth factor given to control the cancer), biologic agents or
radiation therapy within 4 weeks (or 5 half-lives) prior to Day 1 or has not recovered
from AEs due to a previously administered agent

- Use of other investigational drugs within 28 days or at least 5 half-lives before
investigational product administration.

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/09/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2024
Actual
Sample size
Target
Accrual to date
Final
75
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Albury, Australia - Albury
Recruitment hospital [2] 0 0
Principal Investigator - Camperdown
Recruitment hospital [3] 0 0
The Kinghorn Cancer Centre - Darlinghurst
Recruitment hospital [4] 0 0
Scientia Clinical Research - Randwick
Recruitment hospital [5] 0 0
Principal Investigator - Tweed Heads
Recruitment hospital [6] 0 0
Principal Investigator - South Brisbane
Recruitment hospital [7] 0 0
Olivia Newton-John Cancer Research Institute - Heidelberg
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2031 - Randwick
Recruitment postcode(s) [5] 0 0
2480 - Tweed Heads
Recruitment postcode(s) [6] 0 0
4101 - South Brisbane
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Arcus Biosciences, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Gilead Sciences
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1, multicenter, open-label, dose-escalation study to evaluate the safety,
tolerability, PK, PD, and clinical activity of domvanalimab (AB154) as monotherapy and in
combination with zimberelimab (AB122) in participants with advanced solid malignancies.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03628677
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Arcus Biosciences, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03628677