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

• ClinicalTrials.gov Identifier: NCT03629756
• Recruitment Status: Active, not recruiting
• First Posted: August 14, 2018
• Last Update Posted: August 27, 2020
• Sponsor: Arcus Biosciences, Inc.
• Information provided by (Responsible Party): Arcus Biosciences, Inc.

Study Description

Brief Summary:

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.

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; Castration-resistant Prostate Cancer	Drug: AB928; Drug: AB122	Phase 1

Detailed Description:

In the dose-escalation phase, escalating doses of AB928 in combination with AB122 will be assessed in participants with advanced malignancies. Eligible participants will receive oral administration of AB928 as well as IV infusion of AB122. The recommended dose for expansion (RDE) of AB928 will be determined upon completion of the dose-escalation phase.

In the dose-expansion phase, AB928 at RDE in combination with AB122 may be assessed in participants with advanced clear-cell renal cell carcinoma (RCC) or metastatic castrate-resistant adenocarcinoma of the prostate (mCRPC).

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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 44 participants
• Allocation: Non-Randomized
• 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: January 31, 2021
• Estimated Study Completion Date: September 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation; 3+3 design, including a DLT evaluation period. AB928 RDE will be determined in this part with escalating doses of AB928 in combination with a fixed dose of AB122.	Drug: AB928; AB928 is an A2aR and A2bR antagonist.; Drug: AB122; AB122 is a fully human anti-PD-1 monoclonal antibody.
Experimental: Dose Expansion-advanced clear-cell RCC; AB928 at RDE + AB122	Drug: AB928; AB928 is an A2aR and A2bR antagonist.; Drug: AB122; AB122 is a fully human anti-PD-1 monoclonal antibody.
Experimental: Dose Expansion-mCRPC; AB928 at RDE + AB122	Drug: AB928; AB928 is an A2aR and A2bR antagonist.; Drug: AB122; AB122 is a fully human anti-PD-1 monoclonal antibody.

Outcome Measures

Primary Outcome Measures :

1. Percentage of participants with Adverse Events [ Time Frame: From first dose date to 90 days after the last dose (approximately 1 year) ]
2. Percentage of participants who experience a Dose Limiting Toxicity [ Time Frame: From first study treatment administration through Day 28 ]

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 30 and 90 days post last dose (approximately 1 year). ]
2. AB122 Peak Plasma Concentration: Cmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 1 year). ]
3. AB928 Time of Peak Concentration: Tmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 1 year). ]
4. AB122 Time of Peak Concentration: Tmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 1 year). ]
5. Percentage of participants with anti-drug antibodies to AB122 [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), at end of treatment, and 30 and 90 days post last dose (approximately 1 year). ]
6. Progression Free Survival (PFS) as determined by Investigator according to Prostate Cancer Working Group 3 (PCWG3) for prostate adenocarcinoma and per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for all other tumor types [ Time Frame: From start of treatment up to the first occurrence of progressive disease or death from any cause (approximately 6 months, however can be longer). ]
7. Overall Survival (OS) as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types [ Time Frame: From study start of treatment up to death from any cause (up to approximately 1-3 years) ]
8. Duration of Response as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types [ Time Frame: From the date of first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (approximately 1 year) ]
9. Percentage of Participants with Disease Control (complete response, partial response, or stable disease) for >6 months as determined by the Investigator per PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (approximately 1 year) ]
10. Percentage of participants with Objective Response as determined by Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types [ Time Frame: From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1 year) ]

Eligibility Criteria

• 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. 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. Biopsy must not put participant at undue risk and procedure must not be more invasive than a core biopsy.

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 mCRPC.
9. Clear-cell RCC 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, and 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.

Contacts and Locations

Locations

United States, Arizona

Scottsdale Healthcare Hospitals dba HonorHealth

Scottsdale, Arizona, United States, 85258

United States, California

University of California, Los Angeles

Los Angeles, California, United States, 90024

The Angeles Clinic and Research Institute

Los Angeles, California, United States, 90025

United States, Colorado

Rocky Mountain Cancer Centers (Midtown)

Denver, Colorado, United States, 80218

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

QUEST Research Institute

Royal Oak, Michigan, United States, 48073

United States, North Carolina

Carolina BioOncology Institute

Huntersville, North Carolina, United States, 28078

United States, South Carolina

Prisma Health

Greenville, South Carolina, United States, 29605

United States, Texas

Texas Oncology, P.A. - Fort Worth Cancer Center

Fort Worth, Texas, United States, 76104

Texas Oncology, P.A. - San Antonio Medical Center

San Antonio, Texas, United States, 78240

Texas Oncology, P.A. - Tyler

Tyler, Texas, United States, 75702

United States, Washington

Medical Oncology Associates dba Summit Cancer Centers

Spokane, Washington, United States, 99208

Australia, New South Wales

St. George Private Hospital

Kogarah, New South Wales, Australia, 2217

Australia, Queensland

Gallipoli Medical Research Foundation

Greenslopes, Queensland, Australia, 4120

Australia

Cabrini Health Limited

Malvern, Australia, 3144

Sponsors and Collaborators

Arcus Biosciences, Inc.

Investigators

• Study Director: Medical Director; Arcus Biosciences, Inc.

More Information

• Responsible Party: Arcus Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT03629756
• Other Study ID Numbers: AB928CSP0005
• First Posted: August 14, 2018
• Last Update Posted: August 27, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Carcinoma, Merkel Cell; Carcinoma; Carcinoma, Renal Cell; Endometrial Neoplasms; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Squamous Cell; Genital Neoplasms, Female; Urologic Neoplasms; Urologic Diseases; Adenocarcinoma; Kidney Neoplasms; Kidney Diseases; Uterine Neoplasms; Uterine Diseases; Head and Neck Neoplasms; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Carcinoma, Neuroendocrine