Clinical trial NCT03628677: A Study to Evaluate the Safety and Tolerability of AB154 in Participants With Advanced Malignancies
Official title: A Phase 1 Study to Evaluate the Safety and Tolerability of AB154 Monotherapy and Combination Therapy in Participants With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor, Unspecified, Adult
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Gilead Sciences
First posted: 2018-08-14
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation Design
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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 120 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.

Primary outcomes:
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
timeFrame: From First Dose Date to 100 Days After Last Dose
Secondary outcomes:
measure: AB154 Peak Plasma Concentration (Cmax)
timeFrame: 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
measure: Zimberelimab Peak Plasma Concentration (Cmax)
timeFrame: 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
measure: Domvanalimab Time of Peak Concentration (Tmax)
timeFrame: 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
measure: Zimberelimab Time of Peak Concentration (Tmax)
timeFrame: 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
measure: Domvanalimab Area Under the Plasma Concentration Versus Time Curve (AUC)
timeFrame: 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
measure: Zimberelimab Area Under the Plasma Concentration Versus Time Curve (AUC)
timeFrame: 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
measure: Immunogenicity Indicators: Anti-Drug Antibodies (ADA)
timeFrame: Day 1, Day 15, Day 29, Day 43, Day 57, Day 85 and 30 Days After Last Dose, up to 52 weeks
measure: Overall Response Rate
timeFrame: First Dose Date to Progression or Last Tumor Assessment, up to 1 year
measure: Duration of Response
timeFrame: Start Date of Response to First Progression/Death, up to 1 year
measure: Disease Control Rate
timeFrame: First Dose Date to First Progression/Death, up to 1 year
measure: Progression Free Survival
timeFrame: First Dose Date to First Progression/Death, up to 1 year
measure: Overall Survival
timeFrame: First Dose Date to Date of Death, up to 1 year
Other outcomes:
measure: Domvanalimab Receptor Occupancy
timeFrame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
measure: Domvanalimab Immunophenotyping
timeFrame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
measure: Domvanalimab Gene Expression
timeFrame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
measure: Domvanalimab Cytokines
timeFrame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
measure: .Zimberelimab Receptor Occupancy
timeFrame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
measure: Zimberelimab Immunophenotyping
timeFrame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
measure: Zimberelimab Cytokines
timeFrame: : Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
measure: Zimberelimab Gene Expression
timeFrame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141, and 30 Days After Last Dose, up to 52 weeks
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Hinsdale
country: United States
facility: Affinity Health-Hope and Healing Cancer Services, LLC
state: Illinois
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: START
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates, PS (dba Summit Cancer Centers)
state: Washington
city: Darlinghurst
country: Australia
facility: The Kinghorn Cancer Centre - St Vincent Public Hospital
state: New South Wales
city: Tweed Heads
country: Australia
facility: Tweed Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Care Brisbane
state: Queensland
city: Heidelberg
country: Australia
facility: Olivia Newton-John Cancer Research Institute-Austin Hostipal
state: Victoria
Study officials:
affiliation: Arcus Biosciences, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: