A Phase 1 Study to Evaluate the Safety and Tolerability of AB154 Monotherapy and Combination Therapy in Participants With Advanced Malignancies
Overview
- Phase
- Phase 1
- Intervention
- Domvanalimab
- Conditions
- Solid Tumor, Unspecified, Adult
- Sponsor
- Arcus Biosciences, Inc.
- Enrollment
- 75
- Locations
- 10
- Primary Endpoint
- Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
- Status
- Completed
- Last Updated
- last year
Overview
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.
Detailed Description
This is a Phase 1, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, PK, PD, and clinical activity of domvanalimab as monotherapy and in combination with zimberelimab in participants with advanced solid malignancies. In this dose escalation study, participants will receive domvanalimab administered intravenously as monotherapy or in combination with zimberelimab. Treatment will continue until progressive disease, unacceptable toxicity, withdrawal of consent, or other reasons for study drug discontinuation occurs.
Investigators
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.
- •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
- •Confirmation that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor must be obtained
- •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
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.
Arms & Interventions
Domvanalimab Monotherapy
Varying Doses of domvanalimab Monotherapy
Intervention: Domvanalimab
Domvanalimab + zimberelimab Q2W Combination Therapy
Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
Intervention: Domvanalimab
Domvanalimab + zimberelimab Q2W Combination Therapy
Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
Intervention: Zimberelimab
Domvanalimab + zimberelimab Q3W Combination Therapy
Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
Intervention: Domvanalimab
Domvanalimab + zimberelimab Q3W Combination Therapy
Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
Intervention: Zimberelimab
Domvanalimab + zimberelimab Q4W Combination Therapy
Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
Intervention: Domvanalimab
Domvanalimab + zimberelimab Q4W Combination Therapy
Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
Intervention: Zimberelimab
Domvanalimab and Zimberelimab Q6W combination therapy
Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
Intervention: Domvanalimab
Domvanalimab and Zimberelimab Q6W combination therapy
Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
Intervention: Zimberelimab
Fixed dose Domvanalimab Q3W or Q4W and Zimberelimab Q3W, Q4W
Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
Intervention: Domvanalimab
Fixed dose Domvanalimab Q3W or Q4W and Zimberelimab Q3W, Q4W
Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
Intervention: Zimberelimab
Outcomes
Primary Outcomes
Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
Time Frame: From First Dose Date to 100 Days After Last Dose
Number of Participants Treated with domvanalimab or domvanalimab in Combination with zimberelimab with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
Secondary Outcomes
- Domvanalimab Time of Peak Concentration (Tmax)(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)
- Zimberelimab Time of Peak Concentration (Tmax)(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)
- AB154 Peak Plasma Concentration (Cmax)(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)
- Disease Control Rate(First Dose Date to First Progression/Death, up to 1 year)
- Overall Survival(First Dose Date to Date of Death, up to 1 year)
- Zimberelimab Peak Plasma Concentration (Cmax)(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)
- Domvanalimab Area Under the Plasma Concentration Versus Time Curve (AUC)(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)
- Zimberelimab Area Under the Plasma Concentration Versus Time Curve (AUC)(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)
- Immunogenicity Indicators: Anti-Drug Antibodies (ADA)(Day 1, Day 15, Day 29, Day 43, Day 57, Day 85 and 30 Days After Last Dose, up to 52 weeks)
- Overall Response Rate(First Dose Date to Progression or Last Tumor Assessment, up to 1 year)
- Duration of Response(Start Date of Response to First Progression/Death, up to 1 year)
- Progression Free Survival(First Dose Date to First Progression/Death, up to 1 year)