Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06598007
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-09-09
Brief Title:
A Study to Determine the Effect of CT3001 in Patients with Advanced Solid Tumors
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Phase 12a First-In-Human Open-Label Multicenter Dose Escalation and Dose Expansion Study to Determine the Safety Tolerability Pharmacokinetics and Preliminary Efficacy of CT3001 in Patients with Advanced Solid Tumors
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 33 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 bodys 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 bodys 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 23-dioxygenase 1 IDO1-positiveTME-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 efficacydose 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 andor 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 ie 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 ie 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 hisher General Practitioner
Phase 2a Dose Expansion and Efficacy Assessment Once Phase 1 of the study determines the MTD andor 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 andor CBR per RECIST Version 11 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
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 bodys 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 bodys 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 23-dioxygenase 1 IDO1-positiveTME-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 efficacydose 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 andor 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 ie 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 ie 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 hisher General Practitioner
Phase 2a Dose Expansion and Efficacy Assessment Once Phase 1 of the study determines the MTD andor 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 andor CBR per RECIST Version 11 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None