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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04475523
• Other study ID #: CI-8993-101
• Status: Completed
• Phase: Phase 1
• Start date: September 22, 2020
• Est. completion date: May 19, 2023

Study information

• Verified date: October 2023
• Source: Curis, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The plan is to enroll approximately 50 patients with metastatic or unresectable solid tumor malignancy (non-lymphoma) that is considered relapsed and/or refractory to prior therapy into specific dose cohorts to determine the maximum tolerated dose (MTD) of full doses of CI-8993, based on the occurrence of dose limiting toxicities (DLTs) 28 days from the first full dose. Administration is every 2 weeks. To assure patient safety, each patient will receive an initial low dose of CI-8993 (step-dose) one week prior to their first full dose. A Safety Review Committee (SRC) will review all safety data and make cohort escalation/de-escalation decisions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: May 19, 2023
• Est. primary completion date: May 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• CI-8993
CI-8993 is a fully human immunoglobulin (Ig) G1? monoclonal antibody (mAb) against the VISTA ligand

Locations

Country	Name	City	State
Australia	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	The Sarah Cannon Research Institute/Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Curis, Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmax	maximum serum concentration (Cmax)	6 months
Secondary	To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmin	trough serum concentration (Cmin)	6 months
Secondary	To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Tmax	Time to maximum serum concentration	6 months
Secondary	To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Area under the concentration versus time curve (AUC)	area under the concentration-time curve	6 months
Secondary	To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by T 1/2	Serum terminal elimination half-life (T 1/2)	6 months
Secondary	To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by volume of distribution at steady state	volume of distribution at steady state (Vdss)	6 months
Secondary	To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by clearance	Clearance (CL)	6 months
Secondary	To assess anti-drug antibodies (ADA) of CI-8993	Evaluate antibodies to CI-8993 in serum	6 months
Secondary	To assess objective response rate (ORR)	Assess with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)	2 years
Secondary	To assess duration of response (DOR)	Assess with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1 )	2 years
Secondary	To evaluate safety of concomitant drugs that are cytochrome P450 (CYP) enzyme substrates with narrow therapeutic index and drug-drug interaction potential	An analysis of AEs considered related to concomitant drugs that are CYP enzyme substrates with narrow therapeutic index and drug-drug interaction potential	2 years