A Modular Phase 1/2 Study With CT7439 in Participants With Solid Malignancies

A Modular, Multi-Part, Multi-Arm, Phase 1/2 Study to Evaluate the Safety and Tolerability of CT7439 Alone and in Combination With Anticancer Treatments in Participants With Solid Malignancies

This modular, multi-part, multi-arm, Phase 1/2, FIH study allows the evaluation of the safety and tolerability of CT7439, dosed as a monotherapy and in combination with anticancer treatment in participants with solid malignancies.

Study Overview

• Status: Recruiting
• Conditions: Solid Malignancies
• Intervention / Treatment: Drug: CT7439 Capsules (0.5 mg, 1mg, 3mg, 10mg, 15mg, 20mg)

Detailed Description

This study will initially evaluate CT7439 as a monotherapy in participants with locally advanced or metastatic solid malignancies, i.e., Module 1, which includes dose escalation cohort (Part A).

- Part A of Module 1: a First-in Human dose escalation investigating the safety and tolerability of CT7439 to identify the minimum biologically active dose (MBAD) and either maximum tolerated dose (MTD) or maximum feasible dose (MFD) of CT7439 when dosed as monotherapy. SRC, consisting of study investigators and sponsor medical personnel, will be formed to monitor the safety, tolerability, PK, and PDc data during this part of the study. In Part A, cohorts (maximum 6) will be opened sequentially following review from the SRC who will make recommendations on CT7439 dosage selection for subsequent cohorts. Participants will continue to receive IMP until evidence of disease progression, unacceptable toxicities, the participant withdraws their informed consent or is withdrawn from the study, or completion of the primary study analysis.

Further cohort(s) of specific participant sub-populations may be initiated in Module 1 following approval of a protocol amendment.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operations; Phone Number: +353 1 5996873; Email: hello@carricktherapeutics.com

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M20 4GJ
    • Recruiting
    • Research site 05
  • Oxford, United Kingdom, OX37LE
    • Recruiting
    • Research site 04
  • Sutton, United Kingdom, SM2 5PT
    • Recruiting
    • Research site 06
• United States
  • Texas
    • Dallas, Texas, United States, 75230-2571
      • Recruiting
      • Research site 03
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Research site 01
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Research site 02

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Core Inclusion Criteria:

• Histopathologically or cytologically confirmed diagnosis of malignant disease evaluable by RECIST v1.1
• Provision of signed written informed consent before any study-related activities, willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study procedures and willing to permit access to stored historical tumor tissue, prior tumor radiological assessments and tumor biomarker data.
• ECOG performance status of ≤ 2 with no deterioration over the previous 2 weeks.
• Ability to take oral medications and be willing to record daily adherence to the study drug.
• Women either of non-childbearing potential, either confirmed to be post-menopausal or of childbearing potential willing to practice effective contraception for the duration of the study and for minimum 33 days after the last dose of CT7439.
• Sexually active male patients must be willing to refrain from sperm donation from the time of signing informed consent and use condoms with all sexual partners for the duration of the study and for a minimum 93 days months after the last dose of CT7439.
• Estimated life expectancy of at least 3 months, in the opinion of the investigator.

Core Exclusion Criteria:

• Prior therapy with a specific CDK12/13 inhibitor, within any timeframe prior to the first dose of CT7439.
• Participants with any other malignancy that have been active or treated within the past 3 years prior to enrolment, with the exception of cervical intraepithelial neoplasia and non-melanoma skin cancer.
• Any unresolved toxicity (except alopecia) from prior therapy of ≥ 2 Common Terminology Criteria for Adverse Events (CTCAE) Grade.
• Active or documented history of autoimmune disease.
• Any current or prior central nervous system metastases
• Active infection requiring systemic antibiotic, antifungal, or antiviral medication within 14 days prior to first dose of study drug.
• Severe or uncontrolled medical condition or psychiatric condition.
• Human immunodeficiency virus (HIV) infection, unless the study participant on anti-retroviral therapy for at least 4 weeks (28 days) and has not had an opportunistic infection within the past 12 months prior to enrolment.
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, unless participant with HBV patient is on a suppressive antiviral therapy, or participant with HCV has a viral load below the limit of quantification (LoQ).
• Participant is breastfeeding or pregnant.
• Receipt of cytotoxic and/or non- cytotoxic treatment for the malignancy within 28 days before the first dose of IMP.
• Receipt of corticosteroids within 14 days before the first dose of IMP.
• Receipt of any small molecule IMP within 28 days or 5 half-lives, whichever is longer, before the first dose of IMP.
• Receipt of concomitant medications, herbal supplements, or foods that are moderate or strong inhibitors of CYP3A4, CYP2D6, P-gp, or BCRP within a time period before the first dose of IMP based on the drug's elimination half-life, calculated as 5-7 half-lives (minimum 2 days), except for mechanism-based CYP3A4 inhibitors (e.g., clarithromycin, erythromycin), which require a 14-day washout to allow for enzyme re-synthesis.
• Inadequate hepatic, renal and bone marrow function, receipt of a blood transfusion (blood or blood products) within 14 days before the first dose of IMP.
• Persistent (> 4 weeks) severe pancytopenia due to previous therapy rather than to disease (ANC < 0.5 × 109/L or platelets < 50 x 109/L).
• History of cardiac dysfunction and/or presence of clinically significant cardiovascular disease
• Has received a live virus vaccination within 28 days or less of planned treatment start.
• Receipt of concomitant medications, herbal supplements, or foods that are moderate or strong inducers of CYP3A4, CYP2D6, P-gp, or BCRP within a time period before the first dose of IMP of 14 days, except St John's Wort, which requires a 21-day washout.

Additional Module 1 inclusion criteria:

1. Clinically confirmed locally advanced or metastatic solid malignancy for which there is no potentially curative treatment option.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Module 1 Part A (Dose Escalation); Experimental: Module 1 Part A (Dose Escalation) In Part A of Module 1, a minimum of 3 participants and maximum 6 evaluable participants with locally advanced or metastatic solid tumor malignancies will receive CT7439 capsules daily in ascending dose cohorts (maximum 6 cohorts) to identify the minimally biologically active dose (MBAD), planned tolerated dose (MTD) and/or maximum feasible dose (MFD).

Drug: CT7439 Capsules (0.5 mg, 1mg, 3mg, 10mg, 15mg, 20mg); CT7439 capsules administered by mouth once a day as monotherapy with a single starting dose of 1mg in Cohort 1 on Cycle 0 Day 1, followed by a minimum 48 hours treatment -free period before continuous daily dosing in cycles of 28 days (Cycle1 onwards) until DLT or disease progression is observed. Different dosing schedules might be explored in cohorts (BID or intermitting dosing).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of treatment emergent adverse events will be assessed as per CTCAE v5.0.		From first dosing at Cycle 0 to until 30 days after the last dose at Cycle 6. Each cycle is 28 days
Incidence and severity of treatment emergent Laboratory Abnormalities will be assessed as per CTCAE v5.0.		From first dosing at Cycle 0 to until 30 days after the last dose at Cycle 6. Each cycle is 28 days.
Module 1 Part A additional primary outcome measures: Maximum tolerated dose (MTD) determination	Maximum tolerated dose (MTD) defined as the highest dose level at which ≤ 1/6 participants experience DLT in the first cycle. A minimum of 6 participants must be enrolled at the MTD level	Up to 28 days after the first dose of CT7439
Change from Baseline in Eastern Cooperative Oncology Group Cooperative Oncology Group (ECOG) Performance scale.	ECOG has 6 levels (0 to 5). 0=Fully Active (Most Favorable Activity); 1=Restricted activity but ambulatory; 2=Ambulatory but unable to carry out work activities; 3=Limited Self-Care; 4=Completely Disabled, No self-care (Least Favorable Activity); 5=Dead.	Screening, Cycle 0 - Days 1 and Day 2; Cycle 1 - Days 1,8,15; Cycle 2 Day 1 - Cycle 6 Day 1 (each cycle 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Systolic Blood Pressure as determined by blood pressure changes from baseline in systolic blood pressure (measured in mmHg)		Screening, Cycle 0 - Days 1 and Day 2; Cycle 1 - Days 1,8,15; Cycle 2 Day 1 - Cycle 6 Day 1 (each cycle 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Diastolic Blood Pressure as determined by blood pressure changes from baseline in diastolic blood pressure (measured in mmHg)		Screening, Cycle 0 - Days 1 and Day 2; Cycle 1 - Days 1,8,15; Cycle 2 Day 1 - Cycle 6 Day 1 (each cycle 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Heart Rate as determined by heart rate changes from baseline in beats per minute		Screening, Cycle 0 - Days 1 and Day 2; Cycle 1 - Days 1,8,15; Cycle 2 Day 1 - Cycle 6 Day 1 (each cycle 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Body Temperature. as determined by body temperature changes from baseline in Celsius or Fahrenheit		Screening, Cycle 0 - Days 1 and Day 2; Cycle 1 - Days 1,8,15; Cycle 2 Day 1 - Cycle 6 Day 1 (each cycle 28 days) End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Respiratory Rate as determined by respiratory rate changes from baseline in breaths per minute		Screening, Cycle 0 - Days 1 and Day 2; Cycle 1 - Days 1,8,15; Cycle 2 Day 1 - Cycle 6 Day 1 (each cycle 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Oxygen Saturation as determined by changes from baseline in %		Screening, Cycle 0 - Days 1 and Day 2; Cycle 1 - Days 1,8,15; Cycle 2 Day 1 - Cycle 6 Day 1 (each cycle 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Change from Baseline in 12-lead Electrocardiogram (ECG): Heart Rate		From baseline to end of Cycle 6 (each cycle is 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Change from Baseline in 12-lead Electrocardiogram (ECG): PR interval		From baseline to end of Cycle 6 (each cycle is 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Change from Baseline in 12-lead Electrocardiogram (ECG): QRS complex		From baseline to end of Cycle 6 (each cycle is 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Change from Baseline in 12-lead Electrocardiogram (ECG): QT intervals		From baseline to end of Cycle 6 (each cycle is 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Change from Baseline in 12-lead Electrocardiogram (ECG): QTcF intervals (QT Interval Corrected by the Fridericia Formula)		From baseline to end of Cycle 6 (each cycle is 28 days); End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CT7439 PK urine exposure: Cmax	CT7439 PK concentration in urine	At Cycle 0, Day 1. Cycle 0 Day 1 is 24 hours.
Module 1 Part A additional secondary outcome measures - Incidence of Dose Limited Toxicities (DLT)	number of safety events that are not clearly due to the underlying disease or extraneous causes lead to death, or discontinuation of drug treatment due to non-hematological toxicities (Grade 3 or higher) or hematological toxicities (Grade 3 or higher)	At end of Cycle 1 (each cycle is 28 days)
Module 1A secondary outcome measures- Renal clearance	Serum Chemistry creatinine clearance	Screening, Cycle 0 Day 1, Cycle 1 - Day 1,8,15, Cycle 2 - Day 1,15; Cycle 3 - Cycle 6 (28 day each cycle), End of Module/ End of Treatment (within 3 days after last CT7439 dose)
Module 1A secondary outcome measures - Incidence and prevalence of adverse events (AE) resulting in treatment withdrawal	number of adverse events leading to investigational medicinal drug (IMP) withdrawal	From 1st dose of IMP administration at Cycle 0 Day 1 throughout treatment Cycles 1, Cycle 2 - Cycles 6 ( each cycle 28 days) and until End of Treatment (within 3 days of last CT7439 dose) and End of Study (30+/- 7 days after the last CT7439 dose)
Module 1A secondary outcome measures - Best overall response (BOR)	BOR defined as the best response recorded from the randomization start until disease progression or death due to any cause	Up to 24 weeks
Module 1A Overall response rate (ORR)	ORR defined as the proportion of participants who achieved a complete response (CR) or partial response (PR) as per RECIST Version 1.1	Up to 24 weeks
Module 1A Duration of Response (DOR)	DOR defined as the time from the date of first documentation of objective tumor response (CR or PR) to the first documented objective tumor progression per RECIST version 1.1 or censored as defined for PFS	Up to 24 weeks
Module 1A PFS (Progression-free survival) assessment	PFS defined as the time from the first dose of IMP to the date of the first documentation of objective progression of disease (PD) per RECIST version 1.1	Up to 18 months
CT7439 PK Plasma exposure: Cmax	Maximum PK Plasma concentrations and PK parameters for CT7439	PK plasma exposure Cmax: At the end of Cycle 0 Day 1 (cycle 0 is 2 days)
CT7439 PK plasma exposure: C-trough	CT7439 PK plasma parameters pre-dose	From first cycle to end of Cycle 6. (each cycle is 28 days). Up to 6 months
Changes in CT or MRI tumor imaging to monitor anti-tumor activity	the imaging method of CT or MRI will be used at each subsequent visit	Screening, and from C1D1 every 8 weeks +/- 7 days up to Cycle 6 and End of Treatment (within 3 days after last CT7439 dose) and End of Study (30 +/-7 days after the last CT7439 dose)
Module 1 Part A additional secondary outcome measures - determination of recommended Phase 2 Dose (RP2D) and minimally biologically active dose (MBAD) of CT7439 when administered as monotherapy	the CT7439 MBAD is defined as the dose level that will show / achieve a proof of mechanism (PoM) ;a partial or complete RECIST v1.1 assessed response in at least one participant; a clinically significant reduction (in the opinion of the safety review committee (SRC), compared to baseline, in a tumor-specific marker measured in at least one participant	All cohorts. (each cohort is 6 cycles, each cycle is 28 days)
Module 1A secondary outcome measures - Pharmacodynamic evidence of the downstream effects of target engagement	Whole blood RNA assay	From first cycle to end of Cycle 6. (each cycle is 28 days). Up to 6 months.
Cmax: maximum observed plasma concentration of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	COD1 from Time 0 to 48 hours
C24: plasma concentration at 24 hours of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	C0D1 from Time 0 to 24 hours
Tmax: time to maximum observed plasma concentration of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	COD1 from Time 0 to 48 hours
t½: apparent terminal half-life of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	COD1 from Time 0 to 48 hours
λz: apparent terminal elimination rate constant of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	COD1 from Time 0 to 48 hours
AUC0-24: area under the plasma concentration-time curve from Time 0 to 24 hours of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 0 from Time 0 to 24 hours
AUC0-48: area under the plasma concentration-time curve from Time 0 to 48 hours of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 0 from Time 0 to 48 hours
AUC0-t: area under the plasma concentration-time curve from Time 0 to the time of the last measurable concentration of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	From first cycle to end of Cycle 6. (each cycle is 28 days). Up to 6 months.
AUC0-∞: area under the plasma concentration-time curve from Time 0 extrapolated to infinity of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	From first cycle to end of Cycle 6. (each cycle is 28 days). Up to 6 months.
CL/F: apparent plasma clearance of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 0 from Time 0 to 48 hours
Vz/F: apparent volume of distribution of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 0 from Time 0 to 48 hours
MRT: mean residence time of CT7439 (single dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 0 from Time 0 to 48 hours
Css,max: maximum observed plasma concentration at steady state (multiple dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 2 Day 1
Tss,max: Tmax at steady state (multiple dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 2 Day 1
Css,min: minimum observed plasma concentration at steady state (multiple dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 2 Day 1
AUCtau: area under the plasma concentration-time curve in the dosing interval (multiple dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 2 Day 1
CLss/F: CL/F at steady state (multiple dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 2 Day 1
MRTss: MRT at steady state (multiple dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 2 Day 1
TCP: temporal change parameter (multiple dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 2 Day 1
Rac: accumulation ratio (multiple dose)	Pharmacokinetic (PK) parameters calculated based on CT7439 plasma concentrations by using non-compartmental methods.	Cycle 2 Day 1
Amount excreted in urine (Ae) (per collection interval, cumulative and total)	Pharmacokinetic (PK) parameters calculated based on CT7439 urine concentrations by using non-compartmental methods.	Cycle 0, Day 1: 0-4 hr, 4-8 hr and 8-24 hr
Percent or fraction of dose excreted in urine (Fe) (per collection interval, cumulative and total)	Pharmacokinetic (PK) parameters calculated based on CT7439 urine concentrations by using non-compartmental methods.	Cycle 0, Day 1: 0-4 hr, 4-8 hr and 8-24 hr
Renal clearance (CLR)	Pharmacokinetic (PK) parameters calculated based on CT7439 urine concentrations by using non-compartmental methods.	Cycle 0, Day 1: 0-4 hr, 4-8 hr and 8-24 hr

Collaborators and Investigators

• Sponsor: Carrick Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2024
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): March 14, 2027

Study Registration Dates

• First Submitted: September 3, 2024
• First Submitted That Met QC Criteria: September 13, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: August 28, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: First In Human; Cancer Treatment; Solid Malignancies
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CT7439_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No