Clinical Trials /

A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies

NCT03720678

Description:

This is a Phase 1/1b, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of AB928 in combination with mFOLFOX in participants with advanced metastatic gastroesophageal Cancer (GEC) or colorectal cancer (CRC).

Related Conditions:
  • Colorectal Carcinoma
  • Esophagogastric Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
  • Official Title: A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Gastrointestinal Malignancies

Clinical Trial IDs

  • ORG STUDY ID: AB928CSP0003
  • NCT ID: NCT03720678

Conditions

  • GastroEsophageal Cancer
  • Colorectal Cancer

Interventions

DrugSynonymsArms
AB928Dose Escalation
mFOLFOXDose Escalation

Purpose

This is a Phase 1/1b, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of AB928 in combination with mFOLFOX in participants with advanced metastatic gastroesophageal Cancer (GEC) or colorectal cancer (CRC).

Detailed Description

      Dose escalation of AB928 in combination with mFOLFOX at standard doses will be assessed in
      participants with advanced metastatic GEC or CRC. In this dose escalation combination study
      participants will receive oral administration of AB928 as well as iv infusion of mFOLFOX.

      Dose expansion of AB928 in combination with mFOLFOX at standard doses will be assessed in
      participants with advanced metastatic GEC or CRC. The dose of AB928 used will be determined
      based on the findings from the dose-escalation phase.

      Overall duration of treatment will depend on how well the treatment is tolerated. Treatment
      may continue until unacceptable toxicity or progressive disease 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 AB928 in combination with the standard mFOLFOX chemotherapy regimen in participants with gastroesophageal or colorectal cancer.
  • AB928
  • mFOLFOX
Dose Expansion-GEExperimentalThe dose given in expansion will be determined from the dose escalation part. AB928 will be given in combination with the standard mFOLFOX chemotherapy regimen in participants with gastroesophageal cancer
  • AB928
  • mFOLFOX
Dose Expansion-CRCExperimentalThe dose given in expansion will be determined from the dose escalation part. AB928 will be given in combination with the standard mFOLFOX chemotherapy regimen in participants with colorectal cancer
  • AB928
  • mFOLFOX

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female participants ≥ 18 years

          2. Histologically confirmed gastroesophageal cancer or colorectal cancer that is
             metastatic, advanced or recurrent with progression

          3. Participants for whom mFOLFOX is considered appropriate therapy

          4. Must have at least 1 measurable lesion per RECIST v1.1.

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

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

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

          8. 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) or obscure the interpretation of toxicity determination or AEs,
             or concurrent medical condition requiring the use of immunosuppressive medications or
             immunosuppressive doses of systemic or absorbable topical corticosteroids.

          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 30 days after the last dose of AB928 in combination with mFOLFOX.

          5. Any active autoimmune disease or a documented history of autoimmune disease or
             syndrome that required systemic treatment in past 2 years (ie, with use of
             disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for
             vitiligo or resolved childhood asthma/atopy.

               1. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
                  replacement therapy for adrenal or pituitary insufficiency) is not considered a
                  form of systemic treatment.

               2. Participants with asthma who require intermittent use of bronchodilators, inhaled
                  corticosteroids, or local corticosteroid injections will not be excluded from
                  this study. Participants on chronic systemic corticosteroids will be excluded
                  from the study.

          6. Prior malignancy active within the previous 2 years 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.

          7. Oxaliplatin-based therapy as the most recent regimen prior to enrolling in the study,
             except if prior oxaliplatin-based therapy was received as the most recent regimen in
             the adjuvant setting and completed ≥ 6 months prior to study enrollment.

          8. Prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 4
             weeks prior to Day 1 or has not recovered (ie, ≥ Grade 1 or baseline) from AEs due to
             a previously administered agent, except ≤ Grade 2 alopecia or ≤ Grade 2 neuropathy and
             other AEs considered not clinically significant by the Medical Monitor and
             Investigator.

          9. Participants who are eligible for potentially curative available therapies or
             interventions.

         10. Use of other investigational drugs (drugs not marketed for any indication) within 28
             days of 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 90 days after the last dose (Approximately 1 year)
Safety Issue:
Description:Number of Participants Treated with AB928 in Combination with mFOLFOX with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0

Secondary Outcome Measures

Measure:AB928 Pharmacokinetic (PK) Concentration: Cmax
Time Frame:Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and every 30 days until 6 months post last dose (i.e. in total approximately 6 months)
Safety Issue:
Description:Measured using the area under the concentration-time curve from serum plasma collection and analysis
Measure:AB928 Pharmacokinetic (PK) Concentration: Tmax
Time Frame:Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and every 30 days until 6 months post last dose (i.e. in total approximately 6 months)
Safety Issue:
Description:Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis
Measure:Clinical Activity of combination therapy
Time Frame:Recorded at Baseline (Screening), every 8 weeks until progression (approximately 6 months, however can be longer)
Safety Issue:
Description:Tumor assessments over time will be measured using RECIST v1.0.
Measure:AB928 Receptor Occupancy
Time Frame:Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days.
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:AB928 Immunophenotyping
Time Frame:Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days.
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:AB928 Gene Expression
Time Frame:Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days.
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:AB928 Cytokines
Time Frame:Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days.
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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Arcus Biosciences, Inc.

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