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

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ClinicalTrials.gov Identifier: NCT03629756
Recruitment Status : Recruiting
First Posted : August 14, 2018
Last Update Posted : October 25, 2018
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Drug: AB928 Drug: AB122 Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 Dose escalation design.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies
Actual Study Start Date : July 24, 2018
Estimated Primary Completion Date : July 16, 2019
Estimated Study Completion Date : July 16, 2021


Arm Intervention/treatment
Experimental: Dose Escalation
3+3 design, including a DLT evaluation period. Varying doses of AB928 in combination with the selected dose of AB122
Drug: AB928
AB928 is an A2aR and A2bR antagonist.

Drug: AB122
AB122 is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.




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


Secondary Outcome Measures :
  1. 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) ]
    Measured using the area under the concentration-time curve from serum plasma collection and analysis

  2. 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) ]
    Measured using the area under the concentration-time curve from serum plasma collection and analysis

  3. 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) ]
    Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis

  4. 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) ]
    Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis

  5. AB928 PD [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment ]
    pharmacodynamic measures may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from research blood samples

  6. AB122 PD [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment ]
    pharmacodynamic measures may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from research blood samples

  7. AB122 immunogenicity [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment ]
    The number of subjects who develop anti-AB122 antibodies

  8. Clinical Activity of combination therapy [ Time Frame: Recorded at Baseline (Screening), every 8 weeks until progression (approximately 6 months, however can be longer). ]
    Tumor assessments over time will be measured using RECIST v1.0.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female participants ≥ 18 years
  2. 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).
  3. Must have at least 1 measurable lesion per RECIST v1.1.
  4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  5. Must have received standard of care, including potentially curative available therapies or interventions.
  6. Confirm that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor lesion must be obtained.
  7. 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 90 days after the last dose of AB928 in combination with AB122.
  5. 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.
  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. Has had prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 2 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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03629756


Contacts
Contact: Medical Director 510-694-6200 ClinicalTrialInquiry@arcusbio.com

Locations
Australia, New South Wales
Sydney, Australia Recruiting
Sydney, New South Wales, Australia, 2217
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
Sponsors and Collaborators
Arcus Biosciences, Inc.
Investigators
Study Director: Medical Director Arcus Biosciences, Inc.

Responsible Party: Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT03629756     History of Changes
Other Study ID Numbers: AB928CSP0005
First Posted: August 14, 2018    Key Record Dates
Last Update Posted: October 25, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Carcinoma, Squamous Cell
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Endometrial Neoplasms
Head and Neck Neoplasms
Carcinoma, Merkel Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Squamous Cell
Urologic Neoplasms