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 AB154 as monotherapy and in combination with AB122 in participants with advanced solid malignancies.

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Esophagogastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
  • Merkel Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Renal Cell Carcinoma
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

  • Non-small Cell Lung Cancer
  • Squamous Cell Carcinoma of the Head and Neck
  • Renal Cell Carcinoma
  • Breast Cancer
  • Colorectal Cancer
  • Melanoma
  • Bladder Cancer
  • Ovarian Cancer
  • Endometrial Cancer
  • Merkel Cell Carcinoma
  • GastroEsophageal Cancer

Interventions

DrugSynonymsArms
AB154AB154 Monotherapy
AB122AB154 + AB122 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 AB154 as monotherapy and in combination with 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 AB154 as monotherapy and in combination with
      AB122 in participants with advanced solid malignancies. In this dose escalation study,
      participants will receive AB154 administered intravenously as monotherapy or in combination
      with AB122. Treatment will continue until progressive disease, unacceptable toxicity,
      withdrawal of consent, or other reasons for study drug discontinuation occurs.
    

Trial Arms

NameTypeDescriptionInterventions
AB154 MonotherapyExperimentalVarying Doses of AB154 Monotherapy
  • AB154
AB154 + AB122 Combination TherapyExperimentalVarying Doses of AB154 in Combination With the Selected Dose of AB122
  • AB154
  • AB122
Dose Expansion Arm 1ExperimentalRecommended Phase 2 Dose identified in Arm A of AB154 Monotherapy
  • AB154
Dose Expansion Arm 2ExperimentalRecommended Phase 2 Dose identified in Arm B of AB154 in Combination with Selected Dose of AB122
  • AB154
  • AB122
Dose Expansion Arm 3ExperimentalRecommended Phase 2 Dose identified in Arm B of AB154 in Combination with Selected Dose of AB122
  • AB154
  • AB122
Dose Expansion Arm 4ExperimentalRecommended Phase 2 Dose identified in Arm B of AB154 in Combination with Selected Dose of AB122
  • AB154
  • AB122
Dose Expansion Arm 5ExperimentalRecommended Phase 2 Dose identified in Arm B of AB154 in Combination with Selected Dose of AB122
  • AB154
  • AB122

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. Pathologically confirmed non-small cell lung cancer, squamous cell carcinoma of the
             head and neck, renal cell carcinoma, breast cancer, colorectal cancer, melanoma,
             bladder cancer, ovarian cancer, endometrial cancer, Merkel cell carcinoma, or
             gastroesophageal cancer that is metastatic, advanced, or recurrent with progression
             for which no alternative or curative therapy exists or standard therapy is not
             considered appropriate by the participant and treating physician

          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. Must have received standard of care, including potentially curative available
             therapies or interventions

          8. Confirmation that an archival tissue sample is available and ≤ 6 months old; if not, a
             new biopsy of a tumor must be obtained

          9. Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given
             to control the cancer) or biologic agents must have been completed at least 4 weeks
             before investigational product administration, and all AEs have either returned to
             baseline or stabilized

         10. 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

         11. 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

         12. 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

         13. 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. 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

          5. 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
      
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 AB154 or AB154 in Combination with AB122 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 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks
Safety Issue:
Description:Peak Plasma Concentration (Cmax) of AB154
Measure:AB122 Peak Plasma Concentration (Cmax)
Time Frame:Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks
Safety Issue:
Description:Peak Plasma Concentration (Cmax) of AB122
Measure:AB154 Time of Peak Concentration (Tmax)
Time Frame:Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks
Safety Issue:
Description:Time of Peak Concentration (Tmax) of AB154
Measure:AB122 Time of Peak Concentration (Tmax)
Time Frame:Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks
Safety Issue:
Description:Time of Peak Concentration (Tmax) of AB122
Measure:AB154 Area Under the Plasma Concentration Versus Time Curve (AUC)
Time Frame:Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks
Safety Issue:
Description:Area Under the Plasma Concentration Versus Time Curve (AUC) of AB154
Measure:AB122 Area Under the Plasma Concentration Versus Time Curve (AUC)
Time Frame:Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks
Safety Issue:
Description:Area Under the Plasma Concentration Versus Time Curve (AUC) of AB122
Measure:AB154 Receptor Occupancy
Time Frame:Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, 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:AB154 Immunophenotyping
Time Frame:Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, 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:AB154 Gene Expression
Time Frame:Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, 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:AB154 Cytokines
Time Frame:Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, 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:AB122 Receptor Occupancy
Time Frame:Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, 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:AB122 Immunophenotyping
Time Frame:Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, 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:AB122 Cytokines
Time Frame:Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, 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:AB122 Gene Expression
Time Frame:Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, 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: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.

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