Recruiting
Phase 1/2
A Modular Phase 1/2 Study With CT7439 in Participants With Solid Malignancies
Condition(s) studied
Solid Malignancies
Investigational drug(s) / intervention(s)
CT7439 Capsules (0.5 mg, 1mg, 3mg, 10mg, 15mg, 20mg)
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).
Study 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.
Eligibility
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.
Primary outcome measure(s)
- 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.
- Change from Baseline in Eastern Cooperative Oncology Group Cooperative Oncology Group (ECOG) Performance scale. — 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)
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.
- 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)
- Module 1 Part A additional primary outcome measures: Maximum tolerated dose (MTD) determination — Up to 28 days after the first dose of CT7439
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
Trial sites (6)
| Facility | City | Region | Status |
|---|
| Research site 03 |
Dallas |
Texas |
Recruiting |
| Research site 01 |
San Antonio |
Texas |
Recruiting |
| Research site 02 |
Fairfax |
Virginia |
Recruiting |
| Research site 05 |
Manchester |
United Kingdom |
Recruiting |
| Research site 04 |
Oxford |
United Kingdom |
Recruiting |
| Research site 06 |
Sutton |
United Kingdom |
Recruiting |