Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies

NCT04475523 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CI-8993-101
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a phase 1, open-label, multicenter dose-escalation study to determine the RP2D of CI 8993 for administration to patients with relapsed/refractory solid tumors by evaluating the safety and tolerability and characterizing the PK, PD, and anti cancer activity of CI-8993 in this population.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• To determine the maximum tolerated dose of CI-8993

  The highest dose at a schedule, at which the DLT rate during the first cycle of this study (28 days from the first full dose) is \< 33% in at least 6 patients.

  2 years

• Determine the Recommended Phase 2 dose (RP2D)

  The RP2D will be a dose considered to be appropriately safe for a target phase 2 population and exhibit PK and PD characteristics that are favorable and considered likely to support clinical efficacy of CI-8993. The RP2D will be defined by the Safety Review Committee (SRC) based on PK, PD, safety, efficacy results in this study, as well as practical limitations.

  2 years

Secondary Outcomes (11)

• To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmax

  6 months

• To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmin

  6 months

• To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Tmax

  6 months

• To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Area under the concentration versus time curve (AUC)

  6 months

• To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by T 1/2

  6 months

Study Arms (1)

CI-8993 dose escalation

EXPERIMENTAL

Patients will be administered CI-8993 intravenously at a planned infusion rate over 2 hours at planned step-doses and subsequent full doses. The planned schedule of administration is every 2 weeks. The MTD of full doses of CI-8993 will be determined based on the occurrence of DLTs 28 days from the first full dose. Eligible patients may receive CI-8993 at the dose and schedule, according to their assigned cohorts, until disease progression or unacceptable toxicity.

Drug: CI-8993

Interventions

CI-8993 DRUG

CI-8993 is a fully human immunoglobulin (Ig) G1κ monoclonal antibody (mAb) against the VISTA ligand

CI-8993 dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be ≥18 years of age
• Patients must have the following disease related criteria:
• any type of solid tumor malignancy (non-lymphoma) that is metastatic or unresectable and considered relapsed and/or refractory to prior therapy
• must have evaluable disease.
• Archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ and bone marrow function, in the absence of growth factors.
• Fertility criteria:
• Women of childbearing potential (WOCBP) and fertile males with WOCBP partners must use highly effective contraception
• Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction
• Men must agree not to donate sperm
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a highly effective method of birth control.
• Patient must be willing and able to adhere to the prohibitions and restrictions specified in the protocol. Due to the possibility of neurologic events, patient must agree to refrain from engaging in hazardous occupations or activities such as operating heavy or dangerous machinery during the first cycle of treatment.
• Each patient must sign an informed consent form (ICF) indicating that he or she understands the purpose and procedures required for the study and is willing to participate in the study.

You may not qualify if:

• Patient has any of the following medical situations:
• Uncontrolled intercurrent illness including, but not limited to: poorly controlled hypertension; poorly controlled diabetes; ongoing active infection requiring antibiotics or acute infectious illness (including suspected viral infection); symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia considered to increase risk for the patient by the Investigator; psychiatric illness that would limit compliance with study requirement
• Medical illness requiring systemic glucocorticoid use \> 10mg/day prednisone equivalent.
• Patients with any CNS disorder, such as CNS malignancy/metastasis, stroke, transient ischemic attack, or seizure disorder
• Personal or familial history of hemophagocytic lymphohistiocytosis or macrophage activation syndrome
• An autoimmune disease with a history of flares requiring immunosuppressant medications within the past 6 months
• Prior allogeneic organ or bone marrow transplant (BMT).
• Social situation that would limit compliance with study requirements
• Major surgery (eg, requiring general anesthesia) within 4 weeks before the planned first dose of study drug, or not fully recovered from prior surgery, or has surgery planned during the time the patient is expected to participate in the study or within 4 weeks after the last dose of study drug.
• History of positive testing for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-hepatitis C virus) or other clinically active liver disease, or positive testing at screening for HBsAg or anti- hepatitis C virus.
• History of human immunodeficiency virus (HIV) antibody positive
• Patient has had prior therapy meeting the following:
• Anticancer immunotherapy within 3 weeks prior to the first dose of CI-8993
• Prior T Cell Receptor-modified or chimeric antigen receptor T cell (CART) therapy
• Other anticancer therapy, including chemotherapy, targeted therapy, or treatment with an investigational anticancer agent within 2 weeks prior to the first dose of CI-8993

Sponsors & Collaborators

• Curis, Inc.: lead

Study Sites (6)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The Sarah Cannon Research Institute/Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

Related Publications (1)

• Zong L, Mo S, Sun Z, Lu Z, Yu S, Chen J, Xiang Y. Analysis of the immune checkpoint V-domain Ig-containing suppressor of T-cell activation (VISTA) in endometrial cancer. Mod Pathol. 2022 Feb;35(2):266-273. doi: 10.1038/s41379-021-00901-y. Epub 2021 Sep 7.

  PMID: 34493823 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Each patient will be administered a step-dose of CI-8993. If a patient experiences a DLT following the step dose, treatment will be discontinued for that patient. If there are no safety concerns following the step dose, the patient will receive the first full dose of CI-8993 a week later. If none of the 3 patients in each cohort (or 1 in 6 patients) experiences a DLT during the first cycle (28 days following the first full dose), the SRC may clear the next dose level for enrollment.

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 17, 2020
• Study Start: September 22, 2020
• Primary Completion: May 19, 2023
• Study Completion: May 19, 2023
• Last Updated: October 27, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); AU (1)