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

Solid Tumor, Unspecified, Adult Clinical Trial

Official title:

A Phase 1 Study to Evaluate the Safety and Tolerability of AB154 Monotherapy and Combination Therapy in Participants With Advanced Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03628677
• Other study ID #: AB154CSP0001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 12, 2018
• Est. completion date: November 2024

Study information

• Verified date: May 2024
• Source: Arcus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Unspecified, Adult

Intervention

Drug:
• Domvanalimab
Domvanalimabis a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT
• Zimberelimab
Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1

Locations

Country	Name	City	State
Australia	Albury, Australia	Albury	New South Wales
Australia	Principal Investigator	Camperdown	New South Wales
Australia	The Kinghorn Cancer Centre	Darlinghurst	New South Wales
Australia	Olivia Newton-John Cancer Research Institute	Heidelberg	Victoria
Australia	Scientia Clinical Research	Randwick	New South Wales
Australia	Principal Investigator	South Brisbane	Queensland
Australia	Principal Investigator	Tweed Heads	New South Wales
United States	MD Anderson Cancer Center	Houston	Texas
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	START	San Antonio	Texas
United States	Medical Oncology Associates, PS (dba Summit Cancer Centers)	Spokane	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.	Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Domvanalimab Receptor Occupancy	Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
Other	Domvanalimab Immunophenotyping	Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
Other	Domvanalimab Gene Expression	Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
Other	Domvanalimab Cytokines	Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples.	Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
Other	.Zimberelimab Receptor Occupancy	Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
Other	Zimberelimab Immunophenotyping	Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
Other	Zimberelimab Cytokines	Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141 and 30 Days After Last Dose, up to 52 weeks
Other	Zimberelimab Gene Expression	Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141, and 30 Days After Last Dose, up to 52 weeks
Primary	Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0	Number of Participants Treated with domvanalimab or domvanalimab in Combination with zimberelimab with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0	From First Dose Date to 100 Days After Last Dose
Secondary	AB154 Peak Plasma Concentration (Cmax)	Peak Plasma Concentration (Cmax) of domvanalimab	Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary	Zimberelimab Peak Plasma Concentration (Cmax)	Peak Plasma Concentration (Cmax) of zimberelimab	Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary	Domvanalimab Time of Peak Concentration (Tmax)	Time of Peak Concentration (Tmax) of domvanalimab	Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary	Zimberelimab Time of Peak Concentration (Tmax)	Time of Peak Concentration (Tmax) of zimberelimab	Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary	Domvanalimab Area Under the Plasma Concentration Versus Time Curve (AUC)	Area Under the Plasma Concentration Versus Time Curve (AUC) of domvanalimab	Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary	Zimberelimab Area Under the Plasma Concentration Versus Time Curve (AUC)	Area Under the Plasma Concentration Versus Time Curve (AUC) of zimberelimab	Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks
Secondary	Immunogenicity Indicators: Anti-Drug Antibodies (ADA)	Number of Participants who Develop Antidrug Antibodies to AB154 and/or AB122	Day 1, Day 15, Day 29, Day 43, Day 57, Day 85 and 30 Days After Last Dose, up to 52 weeks
Secondary	Overall Response Rate	Number of Participants with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.1	First Dose Date to Progression or Last Tumor Assessment, up to 1 year
Secondary	Duration of Response	Time at Which Response Criteria are Met for Complete Response or Partial Response (Whichever Occurs First) Until the First Date of Recurrence, Progression or Death per RECIST v1.1	Start Date of Response to First Progression/Death, up to 1 year
Secondary	Disease Control Rate	Number of Participants with Complete Response, Partial Response, or Stable Disease for Greater Than 6 Months per RECIST v1.1	First Dose Date to First Progression/Death, up to 1 year
Secondary	Progression Free Survival	Number of Participants Without Disease Progression per RECIST v1.1	First Dose Date to First Progression/Death, up to 1 year
Secondary	Overall Survival	Overall Survival Rate, Defined as Time Between First Dose Date and Date of Death	First Dose Date to Date of Death, up to 1 year