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

Study Description

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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 Design

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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

Arms and Interventions

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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.

Outcome Measures

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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.

Eligibility Criteria

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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.

Contacts and Locations

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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.

More Information

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Responsible Party:	Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier:	NCT03629756 History of Changes
Other Study ID Numbers:	AB928CSP0005
First Posted:	August 14, 2018
Last Update Posted:	December 24, 2018
Last Verified:	December 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