Clinical Trials /

A Study to Evaluate the Safety and Tolerability of AB154 in Participants With Advanced Malignancies

NCT03628677

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
DomvanalimabAB154Domvanalimab + zimberelimab Q2W Combination Therapy
ZimberelimabAB122Domvanalimab + 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

NameTypeDescriptionInterventions
Domvanalimab MonotherapyExperimentalVarying Doses of domvanalimab Monotherapy
  • Domvanalimab
Domvanalimab + zimberelimab Q2W Combination TherapyExperimentalVarying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
  • Domvanalimab
  • Zimberelimab
Domvanalimab + zimberelimab Q3W Combination TherapyExperimentalVarying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
  • Domvanalimab
  • Zimberelimab
Domvanalimab + zimberelimab Q4W Combination TherapyExperimentalVarying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
  • Domvanalimab
  • Zimberelimab
Domvanalimab and Zimberelimab Q6W combination therapyExperimentalVarying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
  • Domvanalimab
  • Zimberelimab
Fixed dose Domvanalimab Q3W or Q4W and Zimberelimab Q3W, Q4WExperimentalVarying Doses of domvanalimab in Combination With Varying Doses of zimberelimab
  • Domvanalimab
  • 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