Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
AB154CSP0001
- NCT ID:
NCT03628677
Conditions
- Solid Tumor, Unspecified, Adult
Interventions
Drug | Synonyms | Arms |
---|
Domvanalimab | AB154 | Domvanalimab + zimberelimab Q2W Combination Therapy |
Zimberelimab | AB122 | Domvanalimab + zimberelimab Q2W Combination Therapy |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Domvanalimab Monotherapy | Experimental | Varying Doses of domvanalimab Monotherapy | |
Domvanalimab + zimberelimab Q2W Combination Therapy | Experimental | Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab | |
Domvanalimab + zimberelimab Q3W Combination Therapy | Experimental | Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab | |
Domvanalimab + zimberelimab Q4W Combination Therapy | Experimental | Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab | |
Domvanalimab and Zimberelimab Q6W combination therapy | Experimental | Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab | |
Fixed dose Domvanalimab Q3W or Q4W and Zimberelimab Q3W, Q4W | Experimental | Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab | |
Eligibility Criteria
Inclusion Criteria:
1. Capable of giving signed informed consent
2. Male or female participants ≥ 18 years of age at the time of screening
3. 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
4. Participants with any pathologically confirmed solid tumor type for which no standard
of care therapy exists
5. 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
6. 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
9. 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
10. 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
12. Adequate organ and marrow function
Exclusion Criteria:
1. Use of any live vaccines against infectious diseases (eg, influenza, varicella) within
4 weeks (28 days) of initiation of investigational product
2. 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)
3. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
4. 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.
5. Participants who require a Legally Authorized Representative (LAR) to provide informed
consent on their behalf.
6. 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
7. 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
8. 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
9. Use of other investigational drugs within 28 days or at least 5 half-lives before
investigational product administration.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0 |
Time Frame: | From First Dose Date to 6 Months After Last Dose |
Safety Issue: | |
Description: | 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 Outcome Measures
Measure: | AB154 Peak Plasma Concentration (Cmax) |
Time Frame: | 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 |
Safety Issue: | |
Description: | Peak Plasma Concentration (Cmax) of domvanalimab |
Measure: | Zimberelimab Peak Plasma Concentration (Cmax) |
Time Frame: | 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 |
Safety Issue: | |
Description: | Peak Plasma Concentration (Cmax) of zimberelimab |
Measure: | Domvanalimab Time of Peak Concentration (Tmax) |
Time Frame: | 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 |
Safety Issue: | |
Description: | Time of Peak Concentration (Tmax) of domvanalimab |
Measure: | Zimberelimab Time of Peak Concentration (Tmax) |
Time Frame: | 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 |
Safety Issue: | |
Description: | Time of Peak Concentration (Tmax) of zimberelimab |
Measure: | Domvanalimab Area Under the Plasma Concentration Versus Time Curve (AUC) |
Time Frame: | 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 |
Safety Issue: | |
Description: | Area Under the Plasma Concentration Versus Time Curve (AUC) of domvanalimab |
Measure: | Zimberelimab Area Under the Plasma Concentration Versus Time Curve (AUC) |
Time Frame: | 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 |
Safety Issue: | |
Description: | Area Under the Plasma Concentration Versus Time Curve (AUC) of zimberelimab |
Measure: | Domvanalimab Receptor Occupancy |
Time Frame: | Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks |
Safety Issue: | |
Description: | Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples |
Measure: | Domvanalimab Immunophenotyping |
Time Frame: | Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks |
Safety Issue: | |
Description: | Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples |
Measure: | Domvanalimab Gene Expression |
Time Frame: | Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks |
Safety Issue: | |
Description: | Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples |
Measure: | Domvanalimab Cytokines |
Time Frame: | Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks |
Safety Issue: | |
Description: | Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples |
Measure: | Zimberelimab Receptor Occupancy |
Time Frame: | Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks |
Safety Issue: | |
Description: | Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples |
Measure: | Zimberelimab Immunophenotyping |
Time Frame: | Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks |
Safety Issue: | |
Description: | Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples |
Measure: | Zimberelimab Cytokines |
Time Frame: | Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks |
Safety Issue: | |
Description: | Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples |
Measure: | Zimberelimab Gene Expression |
Time Frame: | 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 |
Safety Issue: | |
Description: | Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples |
Measure: | Immunogenicity Indicators: Anti-Drug Antibodies (ADA) |
Time Frame: | Day 1, Day 15, Day 29, Day 43, Day 57, Day 85 and 30 Days After Last Dose, up to 52 weeks |
Safety Issue: | |
Description: | Number of Participants who Develop Antidrug Antibodies to AB154 and/or AB122 |
Measure: | Overall Response Rate |
Time Frame: | First Dose Date to Progression or Last Tumor Assessment, up to 1 year |
Safety Issue: | |
Description: | Number of Participants with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.1 |
Measure: | Duration of Response |
Time Frame: | Start Date of Response to First Progression/Death, up to 1 year |
Safety Issue: | |
Description: | Time at Which Response Criteria are Met for Complete Response or Partial Response (Whichever Occurs First) Until the First Date of Recurrence, Progression or Death per RECIST v1.1 |
Measure: | Disease Control Rate |
Time Frame: | First Dose Date to First Progression/Death, up to 1 year |
Safety Issue: | |
Description: | Number of Participants with Complete Response, Partial Response, or Stable Disease for Greater Than 6 Months per RECIST v1.1 |
Measure: | Progression Free Survival |
Time Frame: | First Dose Date to First Progression/Death, up to 1 year |
Safety Issue: | |
Description: | Number of Participants Without Disease Progression per RECIST v1.1 |
Measure: | Overall Survival |
Time Frame: | First Dose Date to Date of Death, up to 1 year |
Safety Issue: | |
Description: | Overall Survival Rate, Defined as Time Between First Dose Date and Date of Death |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Arcus Biosciences, Inc. |
Last Updated
July 23, 2021