Clinical trial NCT06600789: A Modular Phase 1/2 Study with CT7439 in Participants with Solid Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Malignancies
Keywords: Solid Malignancies
Cancer Treatment
First In Human
Lead sponsor: Carrick Therapeutics Limited
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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until evidence of disease progression, unacceptable toxicities, the participant withdraws their informed consent or is withdrawn from the study, or completion of the primary study analysis.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.

Eligibility criteria: 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 enrollment.
* 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 medication, herbal supplement, or food that is a moderate and/or strong inhibitor or inducer of CYP3A4,,strong inhibitor or inducer of CYP2D6 or P-gp or inhibitor of BCRP within 21 days before the first dose of IMP.
* 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 (\&gt; 4 weeks) severe pancytopenia due to previous therapy rather than to disease (ANC \&lt; 0.5 × 109/L or platelets \&lt; 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.

Additional Module 1 inclusion criteria:

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

Primary outcomes:
measure: Incidence and severity of treatment emergent adverse events will be assessed as per CTCAE v5.0.
timeFrame: From first dosing at Cycle 0 to until 30 days after the last dose at Cycle 6. Each cycle is 28 days
measure: Incidence and severity of treatment emergent Laboratory Abnormalities will be assessed as per CTCAE v5.0.
timeFrame: From first dosing at Cycle 0 to until 30 days after the last dose at Cycle 6. Each cycle is 28 days.
measure: Change from Baseline in Eastern Cooperative Oncology Group Cooperative Oncology Group (ECOG) Performance scale.
timeFrame: Screening, Cycle 0 Day 1, Cycle 1- Days 1,8,15; Cycle 2 -Days 1,15; Cycle 3 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 administration)
measure: Systolic Blood Pressure as determined by blood pressure changes from baseline in systolic blood pressure (measured in mmHg)
timeFrame: 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)
measure: Diastolic Blood Pressure as determined by blood pressure changes from baseline in diastolic blood pressure (measured in mmHg)
timeFrame: 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)
measure: Heart Rate as determined by heart rate changes from baseline in beats per minute
timeFrame: 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)
measure: Body Temperature. as determined by body temperature changes from baseline in Celsius or Fahrenheit
timeFrame: 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)
measure: Respiratory Rate as determined by respiratory rate changes from baseline in breaths per minute
timeFrame: 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)
measure: Oxygen Saturation as determined by changes from baseline in %
timeFrame: 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)
measure: Change from Baseline in 12-lead Electrocardiogram (ECG): Heart Rate
timeFrame: From baseline to end of Cycle 6. Each cycle is 28 days
measure: Change from Baseline in 12-lead Electrocardiogram (ECG): PR interval
timeFrame: From baseline to end of Cycle 6. Each cycle is 28 days
measure: Change from Baseline in 12-lead Electrocardiogram (ECG): QRS complex
timeFrame: From baseline to end of Cycle 6. Each cycle is 28 days
measure: Change from Baseline in 12-lead Electrocardiogram (ECG): QT intervals
timeFrame: From baseline to end of Cycle 6. Each cycle is 28 days
measure: Change from Baseline in 12-lead Electrocardiogram (ECG): QTcF intervals (QT Interval Corrected by the Fridericia Formula)
timeFrame: From baseline to end of Cycle 6. Each cycle is 28 days
measure: Module 1 Part A additional primary outcome measures: Maximum tolerated dose (MTD) determination
timeFrame: Up to 28 days after the first dose of CT7439
Secondary outcomes:
measure: CT7439 PK Plasma exposure: Cmax
timeFrame: PK urine exposure Cmax: At the end of Cycle 0 Day 1 (cycle 0 is 2 days)
measure: CT7439 PK plasma exposure: C-trough
timeFrame: Cycle 0 Day 2, Cycle 1 - Days 1, 8, 15; Cycle 2 Day 2; on Cycle 3 day 1 and upwards on Day 1 of every other cycle (each cycle is 28 days)
measure: Changes in CT or MRI tumor imaging to monitor anti-tumor activity
timeFrame: Screening, Cycles 3 Day 1 to Cycle 6 Day 1 (28 days each cycle) and End of Module/ End of Treatment visit (within 3 days after last CT7439 dose)
measure: CT7439 PK urine exposure: Cmax
timeFrame: At Cycle 0, Day 1. Cycle 0 Day 1 is 24 hours.
measure: 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
timeFrame: from cohort 1 to cohort 6. (each cohort is 6 cycles , each cycle is 28 days)
measure: Module 1 Part A additional secondary outcome measures - Incidence of Dose Limited Toxicities (DLT)
timeFrame: At end of Cycle 1 (each cycle is 28 days)
measure: Module 1A secondary outcome measures- Renal clearance
timeFrame: 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)
measure: Module 1A secondary outcome measures - Pharmacodynamic evidence of the downstream effects of target engagement
timeFrame: Screening; Cycle 0 Day 1; Cycle 1 - Day 1, 8 and 15; Cycle 2- Cycle 6 (28 day each cycle) - Day 1; and EOT visit
measure: Module 1A secondary outcome measures - Incidence and prevalence of adverse events (AE) resulting in treatment withdrawal
timeFrame: 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)
measure: Module 1A secondary outcome measures - Best overall response (BOR)
timeFrame: Up to 24 weeks
measure: Module 1A Overall response rate (ORR)
timeFrame: Up to 24 weeks
measure: Module 1A Duration of Response (DOR)
timeFrame: Up to 24 weeks
measure: Module 1A PFS (Progression-free survival) assessment
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Research site 03
state: Texas
city: San Antonio
country: United States
facility: Research site 01
state: Texas
city: Fairfax
country: United States
facility: Research site 02
state: Virginia
city: Manchester
country: United Kingdom
facility: Research site 05
city: Oxford
country: United Kingdom
facility: Research site 04
city: Sutton
country: United Kingdom
facility: Research site 06
Study officials:
References: