Clinical trial NCT04087018: Study to Evaluate Safety and Clinical Activity of AB122 in Biomarker Selected Participants With Advanced Solid Tumors
Official title: A Phase 1b Study to Evaluate the Safety and Clinical Activity of AB122 in Biomarker-Selected Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Strata Oncology
name: Gilead Sciences
First posted: 2019-09-12
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1b open-label study to evaluate the safety and clinical activity of zimberelimab (AB122) in biomarker-selected participants with advanced solid tumors.

Detailed description: The activity of zimberelimab every 3 weeks (Q3W) will be evaluated in molecularly defined patient populations as described by the StrataNGS test (to be performed outside of this study protocol). Participants with any advanced tumor type will be stratified evenly by tumor biomarker status as follows: TMB-H or Strata Immune Signature positive. Each cohort may enroll approximately 40 participants. Following completion of and/or discontinuation from investigational product and follow-up, all participants will be followed for survival.

Eligibility criteria: 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 negative serum or urine pregnancy test every 3 months during the treatment period (women of childbearing potential only).
* Pathologically confirmed tumor that is metastatic, advanced, or recurrent with progression for which no alternative known to improve survival or curative therapy exists. Tumors must be TMB-H or Strata Immune Signature positive.
* Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. 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.
* Prior chemotherapy or certain immune therapies or biologic agents must have been completed at least 4 weeks (28 days) before investigational product administration and all AEs have either returned to baseline or stabilized.
* Previously treated brain or meningeal metastases with no evidence of progression by magnetic resonance imaging (MRI) for at least 4 weeks (28 days) prior to the first dose.
* 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 attenuated vaccines against infectious diseases 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 or obscure the interpretation of toxicity determination or Adverse events (AEs).
* History of myocardial infarction within 6 months or history of arterial thromboembolic event within 3 months of the first dose of investigational agent.
* 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 90 days after the last dose of investigational product.
* Any active or documented history of autoimmune disease or history of a syndrome that required systemic steroids or immunosuppressive medications.
* Any acute gastrointestinal symptoms at the time of screening or admission.
* Prior malignancy active within the previous year except for locally curable cancers that have been apparently cured.
* Prior treatment with an anti-PD-L1 or anti-PD-1 as monotherapy or in combination.
* Prior treatment with temozolomide.
* 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.

Primary outcomes:
measure: Objective response Rate (ORR)
timeFrame: Approximately 12 months
Secondary outcomes:
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
timeFrame: From screening until 90 days after the last dose of investigational product or until initiation of a new systemic anticancer therapy, whichever occurs first, approximately 12 months
measure: Duration of response (DoR)
timeFrame: From the date of initiation of treatment until the date of first documented progression, through completion of the study, approximately 12 months
measure: Time to response (TTR)
timeFrame: From the date of initiation of treatment until the date of first documented response, through completion of the study, approximately 12 months
measure: Disease control rate at 6 months (DCR6)
timeFrame: 6 Months
measure: Progression-free survival at 6 (PFS6)
timeFrame: 6 Months
measure: Progression-free survival at 12 months (PFS12)
timeFrame: 12 Months
measure: Overall survival at 12 months (OS12)
timeFrame: 12 Months
Other outcomes:
Locations:
city: Riverside
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Roseville
country: United States
facility: Kaiser Permanente (NorCal) - Roseville
state: California
city: Newark
country: United States
facility: Christiana Care Health System - Helen F. Graham Cancer Center
state: Delaware
city: Gaithersburg
country: United States
facility: Kaiser Permanente Mid-Atlantic
state: Maryland
city: Saint Louis Park
country: United States
facility: Metro MN CCOP
state: Minnesota
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Cancer Center
state: South Carolina
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
Study officials:
affiliation: Arcus Biosciences, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: