Trial Title:
A Study to Determine the Effect of CT3001 in Patients with Advanced Solid Tumors
NCT ID:
NCT06598007
Condition:
Solid Tumor, Adult
Colorectal Cancer
Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
CT3001
Description:
CT3001 is an Oral Solution, with active pharmaceutical agent, a small molecule inhibitor
of GPR35, formulated with PEG 400, strawberry flavor, and anhydrous ethanol.
Arm group label:
CT3001 100mg
Arm group label:
CT3001 200mg
Arm group label:
CT3001 300mg
Arm group label:
CT3001 500mg
Arm group label:
CT3001 50mg
Arm group label:
CT3001 700mg
Summary:
This is an FIH, multicenter, open-label, dose escalation and dose expansion study of
CT3001, which will be conducted in 2 phases: Phase 1 and Phase 2a. Phase 1 will be a
standard 3+3 dose escalation and dose finding study in patients with advanced solid
tumors for whom there is no available therapy (or patients are not candidates for such
therapy) for the assessment of DLTs at up to 6 dose levels of CT3001. Phase 2a is a dose
expansion study to evaluate the preliminary efficacy of CT3001 in patients with advanced
CRC or PDAC.
Detailed description:
1. Study Rationale
CT3001 is being developed by the Sponsor as a treatment for patients with solid
tumors, including colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma
(PDAC), among others.
Treatments of solid tumors typically include surgery, chemotherapy, radiation, or a
combination approach. Although surgical resection is potentially curative in some
cases, most advanced solid tumor patients are not candidates for this approach and
require multidisciplinary care including chemotherapy or radiation. In addition,
cytotoxic chemotherapy drugs generally lack specificity and can lead to severe side
effects, and radiation alone cannot cure most forms of cancer (Najafi et al. 2021).
Therefore, cancer immunotherapy is becoming increasingly utilized as part of
multidisciplinary cancer care.
The tumor microenvironment (TME) contributes to the development of solid tumors, and
helps shape the body's antitumor immune response (Simsek and Klotzsch 2022, Wang et
al. 2023). The presence and functionality of immune cells, particularly regulatory T
cells (Treg) and cytotoxic T lymphocytes (CTLs), are regulated by cellular and
soluble factors of the TME (Balta et al. 2021). Cancers can hijack the body's
antitumor response by promoting an immunosuppressive TME. Therefore, novel therapies
that restore the antitumor immune response in the TME are of increasing interest in
the treatment of solid tumors (Balta et al. 2021).
The investigational product (IP) in this study is CT3001, which is a first-in-class,
small molecule inhibitor of G-protein coupled receptor 35 (GPR35). GPR35 is an
oncogenic G-protein coupled receptor (GPCR) with abnormally high expression in solid
tumors. GPR35 is tumorigenic and promotes tumor immune escape. CT3001 inhibits GPR35
driven Yes-associated Protein (YAP) oncogene activation. YAP activation can cause
tissue overgrowth and tumorigenesis, whereas YAP inactivation impairs tissue
development and regeneration (Moroishi et al. 2015). YAP is also essential for tumor
immune escape involving Treg function and CTL activity (Lebid et al. 2020, Ni et al.
2018, Stampouloglou et al. 2020). In addition, CT3001 has been shown to suppress
differentiation of Treg cells from naïve CD4+ T cells under indoleamine
2,3-dioxygenase 1 (IDO1)-positive/TME-like culture conditions in vitro and increase
CD8+ T cell tumor infiltration in human peripheral blood mononuclear cell
(PBMC)-reconstituted mice bearing a HT29 colon cancer xenograft.
2. Overall Study Design
This is an FIH, multicenter, open-label, dose escalation and dose expansion study of
CT3001 to determine the safety, tolerability, PK, PD, and preliminary efficacy. The
study will be conducted in multiple sites in the United States (Phase 1, Phase 2a),
and China (Phase 2a, expansion phase).
The study will be conducted in 2 parts: Phase 1 (dose escalation) and Phase 2a
(efficacy/dose expansion).
Phase 1 aims to determine the safety, tolerability, and PK of CT3001 in patients
with advanced solid tumors for whom there is no available therapy likely to confer
clinical benefit, or patients who are not candidates for such therapy.
Once the MTD and the recommended phase 2 dose (RP2D) is established, the study will
be expanded into a dose expansion phase (Phase 2a) in a small cohort of patients
with advanced CRC or PDAC to obtain early proof of concept by biomarker changes
and/or other clinical outcome measures.
3. Overview of Study Schedule
Both Phase 1 and Phase 2a will include a Screening Period, a Treatment Period, and a
Follow-up Period, as follows:
Screening Period (up to 28 days prior to the date of first dose of CT3001): All patients
will be asked to provide informed consent before entering Screening. Following a review
of the inclusion and exclusion criteria, eligible patients will be enrolled (thereby
becoming study participants).
Phase 1 Treatment Period: On Day 1 of Cycle 0 (C0D1), after completing pre-dose
assessments, participants will be administered a single dose of CT3001 and undergo
intensive PK sampling for 48 hours (i.e., through to C0D3). Participants may be
hospitalized from C0D1 through to C0D4, if required by the sites, to perform frequent
blood draws for PK and safety assessments. Dosing with CT3001 will then be paused until
the Safety Monitoring Committee (SMC) can review the safety data. Following SMC review
and approval, participants will then be administered CT3001 orally (QD or BID) from C1D1
to C1D21, with PK sampling occurring on C1D1 to C1D8. Again, participants may be
hospitalized from C1D1 through to C1D8, if required by the sites, to perform frequent
blood draws for PK and safety assessments. From Cycle 2 onwards, participants will
receive CT3001 (orally QD or BID) in repeated 21-day cycles (i.e., Cycle 2, Cycle 3,
Cycle 4, Cycle 5, etc.). Administration of CT3001 will continue for at least 6 months
(approximately 8 cycles) to evaluate CT3001 preliminary efficacy and tolerability. At the
completion of the study, the PI will determine whether to prescribe more appropriate
treatment, restore initial therapy, or to refer the participant to his/her General
Practitioner.
Phase 2a (Dose Expansion and Efficacy Assessment): Once Phase 1 of the study determines
the MTD and/or RP2D, Phase 2a of the study will be initiated. Phase 2a of the study is a
dose expansion study to evaluate the preliminary efficacy of CT3001 in patients with
advanced CRC or PDAC (ORR and/or CBR per RECIST Version 1.1; TTP, DoR, DoCB, and PFS).
During Phase 2a, the safety and tolerability of CT3001, and PK parameters, biomarker
changes (carcinoembryonic antigen for CRC, carbohydrate antigen 19-9 for PDAC) in
patients with advanced CRC or PDAC will be also evaluated / determined.
Number of Participants: Approximately 18 to 36 participants with advanced solid tumors
will be enrolled in Phase 1, and approximately 42 participants with advanced CRC or PDAC
will be enrolled in Phase 2a.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Able to give voluntary informed consent and understand the study and are willing to
follow and complete all the test procedures.
- Aged ≥ 18 years (or adult age as per local regulations).
- Histologically/cytologically confirmed, locally advanced unresectable or metastatic
solid tumors that are refractory to standard therapy, or for whom no standard
therapy exists. Note: In Phase 2a, only participants with locally advanced CRC or
PDAC that are refractory to standard therapy, or for whom no standard therapy
exists, will be enrolled.
- Has measurable disease per RECIST Version 1.1. that was not in a prior radiation or
other locally treated area unless imaging-based progression has been clearly
documented following radiation or other local therapy.
- Life expectancy ≥ 3 months, in the opinion of the PI or designee.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate hematologic, liver, and kidney function as follows:
Bone marrow reserve:
1. Absolute neutrophil count ≥ 1.5 × 10^9/L without growth factor support in the 2
weeks prior to study entry.
2. Hemoglobin ≥9.0 g/dL without transfusion, growth factor support, or other supportive
medication in the 2 weeks prior to study entry.
3. Platelet count ≥ 75 × 10^9/L without transfusion in 2 weeks prior to study entry.
Hepatic function:
1. Serum TBIL < 1.5 × ULN.
2. AST and ALT < 3 × ULN.
Renal function:
Serum creatinine clearance (CrCL) > 60 mL/min, as per the Cockcroft-Gault Equation:
CGGFR = [(140 - age in years) × weight in kg] / (7.2 × serum creatinine in mg/dL) (× 0.85
for females) (for urine protein < 2+; if urine protein > 2+, 24-hour urinary protein
quantity should be measured and must be < 1.0 g).
- Coagulation tests: international normalized ratio (INR) < 1.5, activated partial
thromboplastin time (aPTT) ≤ 1.5 × ULN (Note: for those on oral anticoagulants, an
INR in the range of 2 to 3 is acceptable).
- Participants (both males and females) of childbearing potential should be willing to
use a viable contraception method that is deemed effective by the PI or designee
from Screening, during the study, and for at least 3 months following the last dose
of IP. Postmenopausal women must have been amenorrheal for at least 12 months to be
considered of non-childbearing potential; postmenopausal status, if not known, is to
be confirmed through testing of follicle-stimulating hormone (FSH) levels of ≥ 40
IU/L. Male participants must be willing not to donate sperm until 3 months following
the last IP administration.
Exclusion Criteria:
- Receiving concurrent anticancer treatment (including chemotherapy, targeted drugs,
radiotherapy [excluding the following small-area radiotherapy for bone metastasis],
endocrine therapy, antitumor traditional Chinese Medicine).
- Use of other IP within 5 half-lives of the product (if the IP is a small molecule)
or anti-cancer investigational medical device within two weeks prior to the first
administration of CT3001. Prior use of investigational monoclonal antibody IP can be
permitted upon obtaining an approval from the Sponsor. Use of these investigational
IP or devices are not permitted for the duration of treatment with CT3001.
- Evidence of severe or uncontrolled systemic diseases, infection, or laboratory
finding that in the view of the PI or designee makes it undesirable for the patient
to participate in the trial.
- Females who are pregnant or nursing, or any participant who is planning to become
pregnant (self or partner) at any time during the study, including the Follow-up
Period.
- Has had major surgery or significant traumatic injury within 4 weeks of start of
CT3001; participants have not recovered from the side effects of any major surgery
(defined as requiring general anesthesia) or participant might require major surgery
during the course of the study.
- Has a prolonged QT interval corrected by Fredericia's formula (QTcF interval) of >
470 ms (determined by average of 3 readings on triplicate 12-lead ECG) or has a
history of additional risk factors for Torsade de Pointes (e.g., heart failure,
hypokalemia, family history of long-QT syndrome) or current use of medications that
prolong the QTcF interval.
- Any psychiatric, psychological, familial or geographical condition that, in the
judgment of the PI or designee, may interfere with the treatment and follow-up,
affect compliance or place the participant at high risk of treatment-related
complications will be excluded.
- Blood donation or significant blood loss within 60 days prior to the first
administration of CT3001.
- History of severe allergic or anaphylactic reactions, or sensitivity to the CT3001
or its constituents.
- Vaccination with a live vaccine within 4 weeks prior to the first administration of
CT3001.
- Exposure to any significantly immune suppressing drug (including experimental
therapies as part of a clinical study) within 5 half-lives of the product prior to
the first administration of CT3001; these medications will not be permitted for the
duration of treatment with CT3001.
- Use of any medications with a narrow therapeutics index that are sensitive
substrates of and metabolized mainly through CYP2C8 within 5-half-lives of the
products prior to the first administration of CT3001; these medications will not be
permitted for the duration of treatment with CT3001.
- Use of any gastric acid reducing agents during the time period between 6 hours prior
to and 2 hours after the administration of CT3001.
- Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg),
or human immunodeficiency virus (HIV) antibodies (HIV-1/-2) at Screening, unless the
participant meets 1 of the following criteria:
1. Has chronic hepatitis B virus (HBV) infection or virologically suppressed (VS)
HBV AND has been on suppressive antiviral therapy (unless it is a prohibited
medication per exclusion criteria #12) for at least 4 weeks.
2. Has chronic HCV infection but has completed curative antiviral treatment (note:
patients may be HCV antibody positive but must be HCV RNA negative to be
eligible).
Please note: the eligibility of patients with HBV or HCV infection should be considered
on a case-by-case basis by the PI in consultation with the independent Medical Monitor.
- Anything that the PI considers would jeopardize the safety of the participant,
prevent complete participation in the study, or compromise interpretation of study
data.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Katherine Torres
Phone:
832-750-4997
Email:
KTorres4@mdanderson.org
Contact backup:
Last name:
Jing Peng
Phone:
713-792-2208
Email:
jingpeng@mdanderson.org
Contact backup:
Last name:
Siqing Fu, MD, PhD
Start date:
September 20, 2024
Completion date:
June 30, 2027
Lead sponsor:
Agency:
Crossignal Therapeutics, Inc.
Agency class:
Industry
Source:
Crossignal Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06598007
