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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04475523




Registration number
NCT04475523
Ethics application status
Date submitted
14/07/2020
Date registered
17/07/2020

Titles & IDs
Public title
Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies
Scientific title
Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies
Secondary ID [1] 0 0
CI-8993-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CI-8993

Experimental: CI-8993 dose escalation - 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.


Treatment: Drugs: CI-8993
CI-8993 is a fully human immunoglobulin (Ig) G1? monoclonal antibody (mAb) against the VISTA ligand
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To determine the maximum tolerated dose of CI-8993
Timepoint [1] 0 0
2 years
Primary outcome [2] 0 0
Determine the Recommended Phase 2 dose (RP2D)
Timepoint [2] 0 0
2 years
Secondary outcome [1] 0 0
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmax
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmin
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Tmax
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Area under the concentration versus time curve (AUC)
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by T 1/2
Timepoint [5] 0 0
6 months
Secondary outcome [6] 0 0
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by volume of distribution at steady state
Timepoint [6] 0 0
6 months
Secondary outcome [7] 0 0
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by clearance
Timepoint [7] 0 0
6 months
Secondary outcome [8] 0 0
To assess anti-drug antibodies (ADA) of CI-8993
Timepoint [8] 0 0
6 months
Secondary outcome [9] 0 0
To assess objective response rate (ORR)
Timepoint [9] 0 0
2 years
Secondary outcome [10] 0 0
To assess duration of response (DOR)
Timepoint [10] 0 0
2 years
Secondary outcome [11] 0 0
To evaluate safety of concomitant drugs that are cytochrome P450 (CYP) enzyme substrates with narrow therapeutic index and drug-drug interaction potential
Timepoint [11] 0 0
2 years

Eligibility
Key inclusion criteria
1. Patient must be =18 years of age
2. 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
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Adequate organ and bone marrow function, in the absence of growth factors.
5. 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.
6. 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.
7. 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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
2. 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
* Radiotherapy (excluding limited palliative radiation) within 2 weeks of start of CI-8993
* Unresolved toxicities from previous anticancer therapies above Grade 1.
* Immune-related AE with prior immunotherapy that was Grade 3 or higher.
* Patient has known allergies, hypersensitivity, or intolerance to components of CI 8993
3. Patient receiving therapeutic anticoagulants
4. Fertility exclusions:

* Patient is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study drug; WOCBP must have a negative pregnancy status confirmed by serum pregnancy test at screening and within 72 hours of first dose of study drug.
* Patient is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug.
5. Vaccinated with a live vaccine within 28 days (with the exception of the annual inactivated influenza vaccine) prior to the first dose of study drug

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/05/2023
Sample size
Target
Accrual to date
Final
26
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment postcode(s) [1] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Hampshire
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Curis, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04475523