About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

CT7439 Capsules (0.5 mg, 1mg, 3mg, 10mg, 15mg, 20mg)
Drug
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).

Treatment groups

50 Participants

are divided into 1 treatment group

Group A: Module 1 Part A (Dose Escalation)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Incidence and severity of treatment emergent adverse events will be assessed as per CTCAE v5.0.

Time frame

From first dosing at Cycle 0 to until 30 days after the last dose at Cycle 6. Each cycle is 28 days

2

Incidence and severity of treatment emergent Laboratory Abnormalities will be assessed as per CTCAE v5.0.

Time frame

From first dosing at Cycle 0 to until 30 days after the last dose at Cycle 6. Each cycle is 28 days.

3

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.

Time frame

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)

4

Systolic Blood Pressure as determined by blood pressure changes from baseline in systolic blood pressure (measured in mmHg)

Time frame

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)

Secondary outcomes

1

CT7439 PK Plasma exposure: Cmax

Maximum PK Plasma concentrations and PK parameters for CT7439

Time frame

PK plasma exposure Cmax: At the end of Cycle 0 Day 1 (cycle 0 is 2 days)

2

CT7439 PK plasma exposure: C-trough

CT7439 PK plasma parameters pre-dose

Time frame

From first cycle to end of Cycle 6. (each cycle is 28 days). Up to 6 months

3

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

Time frame

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)

4

CT7439 PK urine exposure: Cmax

CT7439 PK concentration in urine

Time frame

At Cycle 0, Day 1. Cycle 0 Day 1 is 24 hours.

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

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts