Clinical Trials /

A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies

NCT04104672

Description:

This is a Phase 1, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of AB680 in combination with AB122, nab-paclitaxel and gemcitabine in participants with advanced pancreatic cancer.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies
  • Official Title: A Phase 1 Study to Evaluate the Safety and Tolerability of AB680 Combination Therapy in Participants With Gastrointestinal Malignancies

Clinical Trial IDs

  • ORG STUDY ID: AB680CSP0002
  • NCT ID: NCT04104672

Conditions

  • Advanced Pancreatic Cancer

Interventions

DrugSynonymsArms
AB680Dose Escalation
AB122Dose Escalation

Purpose

This is a Phase 1, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of AB680 in combination with AB122, nab-paclitaxel and gemcitabine in participants with advanced pancreatic cancer.

Detailed Description

      Dose escalation of AB680 in combination with AB122, nab-paclitaxel and gemcitabine will be
      assessed in participants with advanced pancreatic cancer. In this dose escalation combination
      study, participants will receive escalating doses of AB680 in combination with AB122 at the
      recommended phase 2 dose (RP2D), and nab-paclitaxel and gemcitabine at standard doses in
      participants with advanced pancreatic cancer. AB680, AB122, nab-paclitaxel and gemcitabine
      are all administered via iv infusion.

      Overall duration of treatment will depend on how well the treatment is tolerated. Treatment
      may continue until progressive disease, unacceptable toxicity or other reasons specified in
      the protocol.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalDose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The dose expansion dose level will be determined in this part with escalating doses of AB680 in combination with AB122 at the recommended phase 2 dose (RP2D) and the standard nab-paclitaxel and gemcitabine chemotherapy regimen in participants with advanced pancreatic cancer.
  • AB680
  • AB122
Dose ExpansionExperimentalThe dose given in dose expansion will be determined from the dose escalation part. AB680 will be given in combination with AB122 at the recommend phase 2 dose (RP2D) and the standard nab-paclitaxel and gemcitabine chemotherapy regimen in participants with advanced pancreatic cancer.
  • AB680
  • 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. Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma

          5. Naïve to any prior treatment, including chemotherapy, biological therapy, or targeted
             therapy for metastatic disease

               1. Prior adjuvant therapy (including chemotherapy and/or radiotherapy) for
                  pancreatic adenocarcinoma is permitted if neoadjuvant or adjuvant therapy was
                  completed at least 6 months prior to study enrollment. Prior adjuvant therapy may
                  include Nab- paclitaxel or gemcitabine

               2. Participants initially diagnosed with locally advanced pancreatic cancer who have
                  undergone chemotherapy then resection and had no evidence of disease are eligible
                  if relapse of metastatic disease has occurred and if the last dose of
                  chemotherapy was received more than 6 months before study entry

          6. 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

          7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

          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. 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) or
             short pulses of corticosteroids (≤ 3 days) may be permitted

         10. 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

         11. 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. 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 90 days after the last dose (approximately 1 year)
Safety Issue:
Description:Number of participants treated with AB680 in combination with AB122 and nab-paclitaxel and gemcitabine with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0

Secondary Outcome Measures

Measure:AB680 Peak Plasma Concentration (Cmax)
Time Frame:Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose
Safety Issue:
Description:Peak Plasma Concentration (Cmax) of AB680
Measure:AB122 Peak Plasma Concentration (Cmax)
Time Frame:Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose
Safety Issue:
Description:Peak Plasma Concentration (Cmax) of AB122
Measure:AB680 Time of Peak Concentration (Tmax)
Time Frame:Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose
Safety Issue:
Description:Time of Peak Concentration (Tmax) of AB680
Measure:AB122 Time of Peak Concentration (Tmax)
Time Frame:Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose
Safety Issue:
Description:Time of Peak Concentration of AB122
Measure:AB680 Area Under the Plasma Concentration Versus Time Curve (AUC)
Time Frame:Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose
Safety Issue:
Description:Area Under the Plasma Concentration Versus Time Curve (AUC) of AB680
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, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose
Safety Issue:
Description:Area Under the Plasma Concentration Versus Time Curve (AUC) of AB122
Measure:Pharmacodynamic Effects of AB680
Time Frame:Day 1, Day 2, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85 and 30 days after last dose
Safety Issue:
Description:Enzymatic Activity of CD73 Measured in Participant Blood Samples
Measure:Immunogenicity Indicators: Anti-Drug Antibodies (ADA)
Time Frame:Day 1, Day 15, Day 29, Day 57, Day 85, 30 days after last dose, and 90 days after last dose
Safety Issue:
Description:Number of Participants who Develop Antidrug Antibodies to 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:Not yet recruiting
Lead Sponsor:Arcus Biosciences, Inc.

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