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

NCT03629756

Description:

This is a Phase 1, 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 AB122 (an anti-PD-1 antibody) in participants with advanced 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
  • Prostate Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: AB928CSP0005
  • NCT ID: NCT03629756

Conditions

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

Interventions

DrugSynonymsArms
AB928Dose Escalation
AB122Dose Escalation

Purpose

This is a Phase 1, open-label, dose-escalation study to evaluate the safety, tolerability, PK, PD and clinical activity of AB928 in combination with AB122 in participants with advanced malignancies.

Detailed Description

      Dose escalation of AB928 in combination with AB122 will be assessed in participants with
      advanced malignancies. In this dose escalation combination study participants will receive
      oral administration of AB928 as well as iv infusion of AB122.

      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 EscalationExperimental3+3 design, including a DLT evaluation period. Varying doses of AB928 in combination with the selected dose of AB122
  • AB928
  • AB122
Dose Expansion-RCCExperimentalSelected Doses of AB928 + AB122
  • AB928
  • AB122
Dose Expansion-CRPCExperimentalSelected Doses of AB928 + AB122
  • AB928
  • AB122

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female participants ≥ 18 years

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

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

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

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

          6. Adequate organ and marrow function

             Dose escalation only:

          7. 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 (reason must be documented in
             medical records).

             Dose expansion only:

          8. Patients with advanced clear-cell RCC or metastatic castration-resistant prostate
             cancer who must have relapsed during anti-PD-1 monotherapy

          9. ccRCC patients may have received up to 2 prior lines of therapy, one of which must
             have included an anti-PD-(L)1 based therapy and must not have progressed within 16
             weeks during an anti-PD-(L)1 therapy.

         10. mCRPC patients must have progressed during or following treatment with an androgen
             synthesis inhibitor who have also had one prior line of a taxane-containing regimen or
             the physician and participant consider the taxane-containing regimen to be
             inappropriate. mCRPC patients must be naive to any immunotherapy (including but not
             limited to anti-PD-(L)1 or anti-CTLA-4 antogonists, sipuleucel-T, etc.).

        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 90 days after the last dose of AB928 in combination with AB122.

          5. Any active or 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.

          6. 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.

          7. Dose escalation: Prior treatment with an anti-PD-L1, anti-PD-1, anti-CTLA-4, or other
             immune checkpoint inhibitor or agonist as a monotherapy or in combination;

          8. Use of other investigational drugs (drugs not marketed for any indication) within 28
             days or at least 5 half-lives (whichever is longer) before investigational product
             administration.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of AB928 combination therapy
Time Frame:From first dose date to 90 days after the last dose (approximately 1 year)
Safety Issue:
Description:Number of treatment emergent adverse events according to CTCAE v5.0.

Secondary Outcome Measures

Measure:AB928 Peak Plasma 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. at 30, 60 and 90 days, and 6 months)
Safety Issue:
Description:Measured using the area under the concentration-time curve from serum plasma collection and analysis
Measure:AB122 Peak Plasma 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. at 30, 60 and 90 days, and 6 months)
Safety Issue:
Description:Measured using the area under the concentration-time curve from serum plasma collection and analysis
Measure:AB928 Time of Peak 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. at 30, 60 and 90 days, and 6 months)
Safety Issue:
Description:Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis
Measure:AB122 Time of Peak 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. at 30, 60 and 90 days, and 6 months)
Safety Issue:
Description:Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis
Measure:AB928 PD
Time Frame:Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment
Safety Issue:
Description:pharmacodynamic measures may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from research blood samples
Measure:AB122 PD
Time Frame:Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment
Safety Issue:
Description:pharmacodynamic measures may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from research blood samples
Measure:AB122 immunogenicity
Time Frame:Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment
Safety Issue:
Description:The number of subjects who develop anti-AB122 antibodies
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 or Prostate Cancer Clinical Trials Working Group 3 (PCWG3)

Details

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

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