Modular Study to Evaluate CT7001 Alone in Cancer Patients With Advanced Malignancies

A Modular, Multipart, Multiarm, Open-label, Phase I/II Study to Evaluate the Safety and Tolerability of CT7001 Alone and in Combination With Anti-cancer Treatments in Patients With Advanced Malignancies

This is a modular, Phase I/II, multicentre study to investigate CT7001 monotherapy in advanced solid malignancies and to further investigate CT7001 as monotherapy or in combination with standard therapy in specific participant groups with Triple Negative Breast Cancer (TNBC), Castrate Resistant Prostate Cancer (CRPC) and in combination with fulvestrant for patients with hormone receptor-positive (HR+ve) / human epidermal growth factor-2 negative (HER2-ve) breast cancer.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Malignancies
• Intervention / Treatment: Drug: CT7001; Drug: Fulvestrant

Detailed Description

Module 1 comprises two sequential parts:

• Part A: First-in-human (FiH) dose escalation investigating the safety and tolerability of CT7001 to identify the minimum biologically active dose (MBAD) and maximum tolerated dose (MTD). Part A also includes a cohort expansion for breast cancer participants only: this includes sequential tumour biopsies for evaluation of pharmacokinetic (PK), pharmacodynamic (PD) and tumour responses. The module is completed.

• Part B: To refine the safety, tolerability, and PK and PD profiles of CT7001 monotherapy in participants with advanced solid malignancies from up to four tumour- specific cohorts, which may include, but is not limited to, triple-negative breast cancer, ovarian cancer, small-cell lung cancer and prostate cancer.

  • Part B, Cohort 1, Triple-Negative Breast Cancer (M1B-1 TNBC) treated with CT7001 as monotherapy. The module is completed.
  • Part B, Cohort 2, Prostate Cancer (M1B-2 CRPC) treated with CT7001 as monotherapy. The module is completed.
• Module 2 is a Phase Ib/II, 3-part safety and efficacy study in participants with hormone- receptor positive (HR+ve) and human epidermal growth factor-2 negative (HER2-ve) breast cancer. This module includes dosing CT7001 in combination with fulvestrant. Module 2 was planned to comprise of 3 parts; Part A (open-label, single-arm, ascending dose study), Part B (double blinded, randomised, placebo-controlled study) and Part C (crossover from Part B). However, only Module 2 Part A was initiated and completed. Therefore, further sections of this record only reflect Module 2 Part A information.
• Module 4 is a study investigating the effect of food on the PK of CT7001 monotherapy in participants with advanced solid malignancies. The module is completed.
• Module 6 was planned as a Phase 1 study to explore the tolerability of, and the total and peak exposure of, an enteric capsule formulation of CT7001 [CT7001(EC)], when given as monotherapy to patients with advanced solid malignancies. Module 6 was not initiated.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Research Site 11
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site 5
  • Glasgow, United Kingdom, G12 0YN
    • Research Site 7
  • Liverpool, United Kingdom, L69 3BX
    • Research Site 10
  • London, United Kingdom, SE1 9RT
    • Research Site 9
  • London, United Kingdom, W1G 6AD
    • Research Site 8
  • London, United Kingdom, W2 1NY
    • Research Site 3
  • Manchester, United Kingdom, M20 4BX
    • Research Site 1
  • Manchester, United Kingdom, M20 4BX
    • Research Site 4
  • Oxford, United Kingdom, OX3 7LE
    • Research Site 2
  • Southampton, United Kingdom, SO16 6YD
    • Research Site 6
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Research Site 54
  • California
    • Beverly Hills, California, United States, 90211
      • Research Site 31
  • Florida
    • Tampa, Florida, United States, 33612
      • Research Site 37
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site 38
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site 34
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Research Site 47
    • Columbus, Ohio, United States, 43212
      • Research Site 39
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site 36
  • Texas
    • Austin, Texas, United States, 78705
      • Research Site 44
    • Dallas, Texas, United States, 75246
      • Research Site 46
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Research Site 48
  • Virginia
    • Salem, Virginia, United States, 24153
      • Research Site 33

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Core Inclusion Criteria:

1. ECOG performance status 0 or 1 with no deterioration over the previous 2 weeks
2. Estimated life expectancy of greater than 12 weeks
3. Ability to swallow and retain oral medication
4. Women either of non-childbearing potential or of childbearing potential willing to practice effective contraception for the duration of the study and for 6 months (Module 1, Module 4) and 24 months (Module 2) after the last dose of CT7001
5. Sexually active male patients must be willing to use condoms with all sexual partners for the duration of the study and for 3 months after the last dose of CT7001.
6. Provision of signed and dated, written informed consent

Core Exclusion Criteria:

1. Any other malignancy that has been active or treated within the past 3 years, with the exception of cervical intraepithelial neoplasia and non-melanoma skin cancer
2. Any unresolved toxicity (except alopecia) from prior therapy of ≥ CTCAE Grade 2
3. Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring steroids for at least 4 weeks before the first dose of investigational product (IP)
4. Refractory nausea and vomiting, chronic gastrointestinal (GI) disease or previous significant bowel resection, with clinically significant sequelae that would preclude adequate absorption of CT7001
5. Uncontrolled seizures
6. Active infection requiring systemic antibiotic, antifungal, or antiviral medication
7. Severe or uncontrolled medical condition or psychiatric condition
8. Active bleeding diatheses
9. Renal transplant
10. Known hepatitis B, hepatitis C, or human immunodeficiency virus infection
11. Breastfeeding or pregnancy
12. Receipt of systemic cytotoxic treatment for the malignancy within 28 days or ≤ 5 half-lives, whichever is shorter before the first dose of IP
13. Receipt of non-cytotoxic treatment for the malignancy within 5 half-lives of the drug before the first dose of IP
14. Receipt of corticosteroids (at a dose > 10 mg prednisone/day or equivalent) within 14 days before the first dose of IP
15. Receipt of any small-molecule investigational medicinal product (IMP) within 28 days or ≤ 5 half-lives, whichever is shorter before the first dose of IP
16. Receipt of any biological IMP (e.g., immune checkpoint blockers, antibodies, nanoparticles) within 42 days before the first dose of IP
17. Receipt of St John's Wort within 21 days before the first dose of IP or of another concomitant medication, herbal supplement, or food that is a strong inhibitor or inducer of CYP3A4, CYP2C19, CYP2D6, or P-glycoprotein (PGP) activity within 14 days before the first dose of CT7001
18. Receipt of a blood transfusion (blood or blood products) within 14 days before the first dose of IP
19. Known hypersensitivity to CT7001 or any excipient of the product

20. Impaired hepatic or renal function as demonstrated by any of the following laboratory values:

    1. Albumin < 30 g/L
    2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × the upper limit of normal (ULN)
    3. > 5.0 × ULN for patients with liver metastases
    4. Total bilirubin > 1.5 × ULN
    5. Serum creatinine > 1.5 × ULN
21. Liver function deteriorating in a manner that would likely make the participant meet the AST, ALT, or bilirubin levels specified above at the time of the first dose of IP
22. Other evidence of impaired hepatic synthesis function

23. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

    1. Absolute neutrophil count (ANC) < 1.5 × 10^9/L
    2. Platelet count < 100 × 10^9/L
    3. Haemoglobin < 90 g/L
24. Persistent (> 4 weeks) severe pancytopenia due to previous therapy rather than to disease (ANC < 0.5 × 10^9/L or platelets < 50 x 10^9/L)
25. Cardiac dysfunction (defined as myocardial infarction within 6 months of study entry, New York Heart Association Class II/III/IV heart failure, unstable angina, unstable cardiac arrhythmias, or left ventricular ejection fraction < 55 percent)
26. Mean resting QT interval corrected for heart rate by the Fridericia formula (QTcF) > 470 msec obtained from 3 electrocardiograms (ECGs) obtained within 5 minutes of each other prior to the first dose
27. Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG (e.g., complete left bundle branch block, third degree heart block). Controlled atrial fibrillation (AF) is permitted
28. Any factor that increases the risk of QTc prolongation or of arrhythmic events (e.g., heart failure, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age)
29. In the opinion of the Investigator, unlikely to comply with study procedures, restrictions, or requirements
30. A history of haemolytic anaemia or marrow aplasia
31. Has received a live-virus vaccination within 28 days or less of planned treatment start

Additional Module 1A Inclusion Criteria:

1. Histological, radiological or cytological confirmation of an advanced non-haematological malignancy not considered to be appropriate for further standard treatment
2. Module 1A biopsy cohort only : at least one tumour suitable for repeat biopsy

Additional Module 1A Exclusion Criteria:

1. International normalised ratio (INR) ≥1.5

Additional Module 1B Inclusion Criteria

1. Histological or cytological confirmation of metastasis or locally advanced tumour
2. At least one line of systemic anti-cancer therapy
3. Disease measurable by RECIST v1.1

Additional Module 1B-1 (TNBC Expansion) Inclusion Criteria:

1. Histologically-confirmed carcinoma of breast not expressing oestrogen receptor (ER) or progesterone receptor (PR) and negative for human epidermal growth factor receptor 2 (HER2)
2. Documented disease progression on or within 6 months of most recent cytotoxic prior cytotoxic chemotherapy
3. Disease measurable by RECIST v1.1
4. Must have received at least one cytotoxic chemotherapy for metastatic/locally advanced disease

Additional Module 1B-1 (TNBC Expansion) Exclusion Criteria:

1. No more than three lines of cytotoxic chemotherapy for metastatic/locally advanced disease
2. No advanced, symptomatic visceral metastases
3. No known symptomatic central nervous system (CNS) metastases, carcinomatous meningitis or leptomeningeal disease
4. Prior exposure to CT7001
5. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Carrick employees directly involved in the conduct of the trial

Additional Module 2A Inclusion Criteria:

1. Women only
2. Pre- or peri-menopausal women must have initiated LHRHa at least 28 days prior to first dose of CT7001/placebo
3. Histologically-confirmed, metastatic or locally advanced, ER+ve and/or PGR+ve and HER2-ve breast cancer
4. Disease measurable by RECIST v1.1
5. Documented objective disease progression while on, or within 6 months after the end of, the most recent therapy
6. Must have received an aromatase inhibitor together with a CDK4/6 inhibitor in the same line of therapy for locally advanced or metastatic disease or for treatment of early breast cancer if the disease-free interval was <12 months.
7. Ability to receive intramuscular injections.

Additional Module 2A Exclusion Criteria:

1. Prior therapy with fulvestrant
2. More than 2 lines of endocrine treatment for locally advanced or metastatic disease
3. Prior treatment with more than one line of cytotoxic chemotherapy for locally advanced or metastatic breast cancer.
4. Patients with liver metastasis will be limited to approximately 30-40% of the enrolled patients. l
5. Known hypersensitivity to CT7001, fulvestrant or any excipient of the investigational products
6. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Carrick employees directly involved in the conduct of the trial

Additional Module 4 Inclusion Criteria:

1. Patients must be able to eat a high-fat meal, as provided by the study site, within a 30-minute period
2. Histological, radiological or cytological confirmation of an advanced non-haematological malignancy not considered to be appropriate for further standard treatment

Additional Module 4 Exclusion Criteria:

1. Patients who were unable to fast for at least 10 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 4; Participants with advanced solid tumours will receive CT7001(samuraciclib) oral monotherapy in a randomized, balanced, single-dose, two-treatment (fed v fasting), two-period, two-sequence crossover study followed by once daily continuous dosing.	Drug: CT7001; Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression; Other Names: Samuraciclib
Experimental: Module 1 Part B-2 Castrate resistant prostate Cancer (CRPC) Expansion; Participants with castrate resistant prostate cancer will receive CT7001(samuraciclib) as oral monotherapy at the dose, frequency and schedule recommended from Module 1 Part A.	Drug: CT7001; Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression; Other Names: Samuraciclib
Experimental: Module 1 Part B-1 Triple-negative breast cancer (TNBC) Expansion; Participants with locally advanced or metastatic triple-negative breast cancer (TNBC) will receive CT7001(samuraciclib) as oral monotherapy at the dose, frequency and schedule recommended from Module 1 Part A.	Drug: CT7001; Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression; Other Names: Samuraciclib
Experimental: Module 2 Part A; Participants with locally advanced or metastatic HR+ve and HER2-ve breast cancer will receive CT7001 (samuraciclib) at the dose, frequency and schedule recommended from Module 1 part A and will receive Fulvestrant solution in pre-filled syringe for intramuscular (IM) injection	Drug: CT7001; Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression; Other Names: Samuraciclib; Drug: Fulvestrant; Administered as 2 x 250mg intramuscular (IM) gluteal injections on Day 1, Day 15, Day 28 and every 28 days thereafter.; Other Names: Faslodex
Experimental: Module 1 Part A Multiple ascending dose cohort and Paired Biopsy Breast Cancer Expansion Cohort; Module 1 Part A Multiple ascending dose cohort: Participants with advanced solid tumours receive CT7001 (samuraciclib) as oral monotherapy, in ascending dose cohorts, to identify the maximum tolerated dose (MTD), minimally biologically active dose (MBAD) and recommended dose for Phase II testing (RP2D). Following completion of the dose escalation part of Module 1A, participants to receive safe, tolerable and MBAD of CT7001 for the paired biopsy expansion cohort. Module 1 Part A Paired Biopsy Breast Cancer Expansion Cohort: Participants with locally advanced or metastatic breast cancer will receive CT7001 (samuraciclib) as oral monotherapy at the minimally biologically active dose (MBAD) and recommended dose for Phase II testing (RP2D).	Drug: CT7001; Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression; Other Names: Samuraciclib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-Emergent Adverse Events and Laboratory Abnormalities (Safety and Tolerability)	Treatment-emergent adverse events (TEAEs) are defined as those AEs which occur from Cycle 0 Day 1/Cycle 1 Day 1 of the study module to 28 days after the last dose of CT7001 in a module. Results reported below for Participants with one or more related TEAEs.	Screening to end of study (28-35 calendar days after end of treatment). End of treatment at disease progression, unacceptable toxicity or withdrawal of consent. Average time on study 142.6 days (range 9 - 1135 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration of CT7001 (Cmax)	Cmax is the maximum observed plasma concentration of CT7001 following oral dosing.	After the first dose and during the dosing period (from the time of dose administration to 24 hours) for Module 1A cohorts. Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24, 48, 72, 120 and 168 hours post dose for Module 4 Cohorts.
Area Under the Curve (AUC)	Area under the plasma concentration-time curve representing the total drug exposure over time.	After the first dose and during the dosing period (from the time of dose administration to 24 hours) for Module 1A. Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24, 48, 72, 120 and 168 hours post dose for Module 4 Cohorts.
Mean Trough Plasma Pharmacokinetic Concentrations for CT7001	Mean Trough Plasma Pharmacokinetic Concentrations is the lowest concentration of a drug in the bloodstream during a dosing interval. Timeframe: On study sampling: M1A - Day 1, 8, 15, 22, 29, 43, 50, every 21 days thereafter and EOT. M1B-1 and M1B-2: Day1, 8, 22, every 21 days thereafter and EOT. M2A: Day1, 15, 29, 57, every 56 days thereafter and EOT. M4: Day 1, 8, 15, 22, 29, 36, every 21 days thereafter and EOT.	From enrolment (Day 1) through to disease progression, unacceptable toxicity or withdrawal of consent, whichever came first (EOT). Assessed up to 1135 days. On study pre-dose sampling for all modules (see outcome measure description).
Mean Trough Plasma Pharmacokinetic Concentrations for Fulvestrant (Module 2A)	Mean trough plasma PK concentrations refer to the lowest concentration of a drug in the bloodstream during a dosing interval.	From enrolment through to disease progression, unacceptable toxicity or withdrawal of consent, whichever came first (EOT). Pre-dose sampling at Day 1, 15, 29, 57 and every 56 days thereafter and EOT. Assessed up to 848 days.
Anti-tumour Activity According to RECIST v1.1-Best Objective Response	Antitumour activity endpoints were analysed using the evaluable for Response population (any patient with at least one post baseline RECIST assessment). Best objective response is defined as the best response recorded from the start of study treatment to the end of treatment, including any assessments for confirmation after the end of treatment. Percentage of participants with each response calculated was based on the total number of participants with a baseline RECIST assessment. Timeframe: Scan frequency - Modules 1A and 4 (every 6 weeks); Modules 1B-1 and 2A (every 8 weeks first year, every 12 weeks thereafter); Module 1B-2 (every 8 weeks for the 6 months, every 12 weeks thereafter).	From enrolment (Day 1) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1135 days (162 weeks). Frequency in outcome measure description.
Anti-tumour Activity According to RECIST v1.1-Progression Free Survival	Antitumour activity endpoints were analysed using the evaluable for Response population based on RECIST assessment. Progression free survival is defined as the time from start of treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant had withdrawn from therapy or had received another anti-cancer therapy prior to progression. Participants who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.	From enrolment (Day 1) until the date of first documented progression or date of death from any cause, whichever came first. Modules 1B-1 and 2A: every 8 weeks first year, every 12 weeks thereafter) assessed up to 848 days (121 weeks).
Anti-tumour Activity According to RECIST v1.1-Clinical Benefit Rate (CBR)	Antitumour activity endpoints were analysed using the evaluable for Response population based on RECIST assessment. Clinical Benefit Rate (CBR) is defined as the percentage of subjects with a confirmed objective response of complete response or partial response, or stabilisation of disease for at least 24 weeks.	From enrolment (Day 1) until the date of first documented progression or date of death from any cause, whichever came first. Module 2A: every 8 weeks first year, every 12 weeks thereafter) assessed up to 848 days (121 weeks).

Collaborators and Investigators

• Sponsor: Carrick Therapeutics Limited
• Investigators: Principal Investigator: Matthew Krebs, MBChB PhD, The Christie Hospital, Manchester, UK

Publications and helpful links

General Publications

• Sava GP, Fan H, Coombes RC, Buluwela L, Ali S. CDK7 inhibitors as anticancer drugs. Cancer Metastasis Rev. 2020 Sep;39(3):805-823. doi: 10.1007/s10555-020-09885-8.
• Coombes RC, Howell S, Lord SR, Kenny L, Mansi J, Mitri Z, Palmieri C, Chap LI, Richards P, Gradishar W, Sardesai S, Melear J, O'Shaughnessy J, Ward P, Chalasani P, Arkenau T, Baird RD, Jeselsohn R, Ali S, Clack G, Bahl A, McIntosh S, Krebs MG. Dose escalation and expansion cohorts in patients with advanced breast cancer in a Phase I study of the CDK7-inhibitor samuraciclib. Nat Commun. 2023 Jul 24;14(1):4444. doi: 10.1038/s41467-023-40061-y.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2017
• Primary Completion (Actual): December 15, 2022
• Study Completion (Actual): December 15, 2022

Study Registration Dates

• First Submitted: November 27, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (Actual): December 6, 2017

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Neoplasms
• Additional Relevant MeSH Terms: Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant
• Other Study ID Numbers: CT7001_001; 2017-002026-20 (EudraCT Number)

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