Solid TumorPhase 1NCT04475523
Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies
A Phase 1 study testing CI-8993 in people with Solid Tumor, run by Curis, Inc. at 6 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- CI-8993
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 22 Sep 2020to 19 May 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
- 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
- Patient receiving therapeutic anticoagulants
- 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.
- 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
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
The Sarah Cannon Research Institute/Tennessee Oncology
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Australia1 site
Peninsula & South Eastern Haematology and Oncology Group
Frankston, Victoria, 3199
About this study
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.
Read the detailed 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.
- Conditions
- Solid Tumor
- Being tested
- CI-8993
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CI-8993Drug
CI-8993 is a fully human immunoglobulin (Ig) G1κ monoclonal antibody (mAb) against the VISTA ligand
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: CI-8993 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 2 years
Secondary outcomes (11)
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmax
maximum serum concentration (Cmax)
Measured: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmin
trough serum concentration (Cmin)
Measured: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Tmax
Time to maximum serum concentration
Measured: 6 months
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
Measured: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by T 1/2
Serum terminal elimination half-life (T 1/2)
Measured: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by volume of distribution at steady state
volume of distribution at steady state (Vdss)
Measured: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by clearance
Clearance (CL)
Measured: 6 months
To assess anti-drug antibodies (ADA) of CI-8993
Evaluate antibodies to CI-8993 in serum
Measured: 6 months
To assess objective response rate (ORR)
Assess with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Measured: 2 years
To assess duration of response (DOR)
Assess with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1 )
Measured: 2 years
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2020
- Study start22 Sep 2020
- Primary completion19 May 2023
- Study completion19 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Curis, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04475523
- Sponsor's protocol ID
- CI-8993-101
- Status last verified
- Oct 2023
- First submitted
- 14 Jul 2020
- Last updated
- 27 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34493823
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies
- ClinicalTrials.gov ID
- NCT04475523
- Acronym / sponsor ID
- CI-8993-101
- Conditions
- Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Curis, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Sep 2020 (actual)
- Primary completion
- 19 May 2023 (actual)
- Study completion
- 19 May 2023 (actual)
- First posted
- 17 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| CI-8993 dose escalation | Experimental | Drug: CI-8993Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patient must be ≥18 years of age
- Patients must have the following disease related criteria:
- 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:
Key exclusion criteria (24 listed)
- Patient has any of the following medical situations:
- Patient has had prior therapy meeting the following:
- Patient receiving therapeutic anticoagulants
- Fertility exclusions:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CI-8993CI-8993 is a fully human immunoglobulin (Ig) G1κ monoclonal antibody (mAb) against the VISTA ligand | Drug | CI-8993 dose escalation |
Primary outcome
To determine the maximum tolerated dose of CI-8993
Time frame: 2 years
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.
Determine the Recommended Phase 2 dose (RP2D)
Time frame: 2 years
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.
11 secondary outcomes
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmax
Time frame: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmin
Time frame: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Tmax
Time frame: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Area under the concentration versus time curve (AUC)
Time frame: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by T 1/2
Time frame: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by volume of distribution at steady state
Time frame: 6 months
To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by clearance
Time frame: 6 months
To assess anti-drug antibodies (ADA) of CI-8993
Time frame: 6 months
To assess objective response rate (ORR)
Time frame: 2 years
To assess duration of response (DOR)
Time frame: 2 years
To evaluate safety of concomitant drugs that are cytochrome P450 (CYP) enzyme substrates with narrow therapeutic index and drug-drug interaction potential
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2023.
- Derived from this study: PubMed 34493823Zong 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CI-8993 in people with Solid Tumor, run by Curis, Inc. at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the maximum tolerated dose of CI-8993 (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04475523, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2023.