A Study to Evaluate the Safety and Tolerability of AB154 in Participants With Advanced Malignancies

Arcus Biosciences

Status and phase: Active, not recruiting; Phase 1

Conditions: Solid Tumor, Unspecified, Adult

Treatments: Drug: Domvanalimab; Drug: Zimberelimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03628677

AB154CSP0001

Details and patient eligibility

About

This is a Phase 1, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, PK, PD, and clinical activity of domvanalimab (AB154) as monotherapy and in combination with zimberelimab (AB122) in participants with advanced solid malignancies.

Full description

This is a Phase 1, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, PK, PD, and clinical activity of domvanalimab as monotherapy and in combination with zimberelimab in participants with advanced solid malignancies. In this dose escalation study, participants will receive domvanalimab administered intravenously as monotherapy or in combination with zimberelimab. Treatment will continue until progressive disease, unacceptable toxicity, withdrawal of consent, or other reasons for study drug discontinuation occurs.

Enrollment: 75 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Capable of giving signed informed consent
• Male or female participants ≥ 18 years of age at the time of screening
• Negative serum pregnancy test at screening and prior to dosing on Cycle 1 Day 1; negative serum or urine pregnancy test on the first day of each subsequent treatment period
• Participants with any pathologically confirmed solid tumor type for which no standard of care therapy exists
• Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The measurable lesion must be outside of a radiation field if the participant received prior radiation
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 7. Confirmation that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor must be obtained 8. Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days) before investigational product administration. Physiologic doses of corticosteroids ≤ 10 mg/day of prednisone or its equivalent may be permitted
• Prior surgery that required general anesthesia or other major surgery as defined by the Investigator must be completed at least 4 weeks before investigational product administration
• Negative tests for hepatitis B surface antigen, hepatitis C virus antibody (or hepatitis C qualitative ribonucleic acid [RNA; qualitative]), and human immunodeficiency virus (HIV)-1 and HIV-2 antibody at screening
• Adequate organ and marrow function

Exclusion criteria

• Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product
• 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)
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• 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 100 days after the last dose of domvanalimab as monotherapy and in combination with zimberelimab.
• Participants who require a Legally Authorized Representative (LAR) to provide informed consent on their behalf.
• 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
• 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
• Has had prior chemotherapy, targeted small-molecule therapy, immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer), biologic agents or radiation therapy within 4 weeks (or 5 half-lives) prior to Day 1 or has not recovered from AEs due to a previously administered agent
• Use of other investigational drugs within 28 days or at least 5 half-lives before investigational product administration.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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75 participants in 6 patient groups

Domvanalimab Monotherapy

Experimental group

Description:

Varying Doses of domvanalimab Monotherapy

Treatment:

Drug: Domvanalimab

Domvanalimab + zimberelimab Q2W Combination Therapy

Experimental group

Description:

Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Treatment:

Drug: Zimberelimab

Drug: Domvanalimab

Domvanalimab + zimberelimab Q3W Combination Therapy

Experimental group

Description:

Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Treatment:

Drug: Zimberelimab

Drug: Domvanalimab

Domvanalimab + zimberelimab Q4W Combination Therapy

Experimental group

Description:

Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Treatment:

Drug: Zimberelimab

Drug: Domvanalimab

Domvanalimab and Zimberelimab Q6W combination therapy

Experimental group

Description:

Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Treatment:

Drug: Zimberelimab

Drug: Domvanalimab

Fixed dose Domvanalimab Q3W or Q4W and Zimberelimab Q3W, Q4W

Experimental group

Description:

Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Treatment:

Drug: Zimberelimab

Drug: Domvanalimab