CT7439 for Cancer

Recruiting at 6 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Carrick Therapeutics Limited

Must not be taking: Antibiotics, Antifungals, Antivirals, Corticosteroids

Disqualifiers: Autoimmune disease, CNS metastases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 28

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment, CT7439, to evaluate its safety and effectiveness, both alone and in combination with other cancer treatments. It targets individuals with advanced solid tumors, which are cancers that have spread and lack a known cure. The trial seeks participants diagnosed with solid tumor cancer that other treatments cannot cure. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but you cannot take certain medications like corticosteroids, specific inhibitors or inducers of CYP3A4, CYP2D6, P-gp, or BCRP, and certain treatments within specified timeframes before starting the trial. Check with the trial team for details on your specific medications.

Is there any evidence suggesting that CT7439 is likely to be safe for humans?

Research has shown that CT7439 is under careful study for its safety and potential side effects. This treatment is in the early testing stages, so researchers are still determining its safety for people. The FDA has approved testing the drug in humans, marking a positive first step.

The current main goal is to find the safest dose that remains effective. In these early studies, researchers are testing different doses to identify which ones patients can best tolerate. As this is an early-stage trial, detailed safety information may not yet be available. However, researchers are taking steps to ensure safety as they learn more about people's responses to CT7439. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CT7439 because it offers a fresh approach to treating advanced or metastatic solid tumors. Most existing cancer treatments, like chemotherapy and radiation, work by attacking rapidly dividing cells, which can also harm healthy cells. In contrast, CT7439 aims to precisely target cancer cells with a novel mechanism that minimizes damage to normal tissues. This targeted approach could lead to fewer side effects and potentially more effective outcomes for patients.

What evidence suggests that CT7439 might be an effective treatment for cancer?

Research has shown that CT7439 could be a promising treatment for solid tumors. CT7439 blocks certain proteins, CDK12/13, that help cancer cells grow and survive. Early studies suggest that inhibiting these proteins can slow or stop tumor growth, especially in cancers where these proteins are highly active. In this trial, participants will receive CT7439 in a dose-escalation study to determine the minimally biologically active dose (MBAD), maximum tolerated dose (MTD), and/or maximum feasible dose (MFD). Although direct evidence on its effectiveness is still being gathered, these early results strongly support further research. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals with solid tumors who are eligible to try a new treatment. Specific eligibility details aren't provided, but typically participants should be adults with measurable cancer and good organ function, not currently responding to standard treatments.

Inclusion Criteria

Estimated life expectancy of at least 3 months, in the opinion of the investigator

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

My physical ability hasn't worsened in the last 2 weeks.

Exclusion Criteria

I have a history of heart problems or significant heart disease.

Participant is breastfeeding or pregnant

I haven't taken any drugs or supplements that strongly affect drug metabolism enzymes in the last 21 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

First-in-Human dose escalation to determine the minimum biologically active dose and maximum tolerated dose of CT7439

Up to 24 weeks

Multiple visits per cycle, each cycle is 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CT7439

Trial Overview The study tests different doses of CT7439 capsules (0.5 mg, 1mg, 3mg) alone or combined with other cancer treatments in people with solid malignancies. It's an early-stage trial to assess safety and how well the body tolerates the drug.

How Is the Trial Designed?

Group I: Module 1 Part A (Dose Escalation) Experimental Treatment 1 Intervention

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), maximum tolerated dose (MTD) and/or maximum feasible dose (MFD).

Who Is Running the Clinical Trial?

Carrick Therapeutics Limited

Lead Sponsor

Trials

5

Recruited

290+

Published Research Related to This Trial

A review of 166 phase III randomized clinical trials published between 2011 and 2013 revealed frequent misreporting of adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0), indicating a significant issue in adherence to established guidelines.

Inappropriate grading of toxicities was common, with serious conditions like febrile neutropenia often graded too low, and less severe conditions like alopecia graded too high, which could mislead clinicians and affect treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use and misuse of common terminology criteria for adverse events in cancer clinical trials. Zhang, S., Liang, F., Tannock, I.[2018]

In a phase I study involving 27 patients with locally recurrent rectal cancer, the maximum tolerated dose (MTD) of CPT-11 was established at 60 mg/m2, with the recommended dose for future trials set at 50 mg/m2 due to manageable side effects.

The combination of CPT-11 with UFT/LV and radiation therapy was found to be feasible, with significant adverse events including grade 3 diarrhea and neutropenia, but no grade 4 adverse events were reported, indicating a relatively safe profile for this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of oral UFT/leucovorin and irinotecan, plus radiation for locally recurrent rectal cancer. Ikeda, M., Sekimoto, M., Fukunaga, Y., et al.[2020]

The combination of CPT-11 and capecitabine showed a higher overall response rate (51.9%) and longer time to progression (12.5 months) compared to CPT-11 with fluorouracil (31.3% response rate and 8.4 months TTP), indicating greater efficacy for treating advanced colorectal cancer.

The safety profile was favorable, with only 3.0% of patients experiencing grade III side effects and no therapy-related deaths, suggesting that CPT-11 combined with capecitabine is not only more effective but also associated with fewer severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Irinotecan combined with fluoropyrimidine in treatment for advanced/metastatic colorectal carcinoma]. Yu, BM., Wu, WQ.[2018]

In a phase II study involving 70 patients with advanced non-small cell lung cancer (NSCLC), the combination of irinotecan (CPT-11) and cisplatin resulted in a promising objective response rate of 52%, with one complete response and 32 partial responses.

The treatment demonstrated a median survival time of 44 weeks and a 1-year survival rate of 33%, while the major toxicities included leucopenia and diarrhea, affecting a significant portion of patients but deemed acceptable in the context of the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of combination of CPT-11 and cisplatin for advanced non-small-cell lung cancer. CPT-11 Lung Cancer Study Group. Masuda, N., Fukuoka, M., Fujita, A., et al.[2019]

This ongoing multicentre study in Japan aims to collect patient-reported outcomes on immune-related adverse events (irAEs) in patients with gastrointestinal cancer, lung cancer, and malignant pleural mesothelioma treated with immune checkpoint inhibitors (ICIs), using the PRO-CTCAE tool over a period of up to 48 weeks.

As of October 2022, 141 out of a target of 260 patients have been enrolled, indicating a significant effort to understand the safety profile of ICIs from the patients' perspectives, which is currently lacking in existing research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Registry study of immune-related adverse events using electronic patient-reported outcome in patients with cancer receiving immune checkpoint inhibitors: protocol for a multicentre cohort study. Hirata, T., Kawaguchi, T., Azuma, K., et al.[2023]

In a meta-analysis of 143 phase 3 randomized controlled trials involving 88,603 patients with advanced cancers, experimental drugs showed improved progression-free survival (PFS) and overall survival (OS) compared to control groups, with hazard ratios of 0.80 and 0.87, respectively.

However, these experimental treatments were associated with higher rates of toxic deaths, treatment discontinuations without progression, and severe adverse events, indicating that while they may be more effective, they also come with increased safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and tolerability of drugs studied in phase 3 randomized controlled trials in solid tumors over the last decade. Ribnikar, D., Goldvaser, H., Veitch, ZW., et al.[2021]

The combination of irinotecan (SN-38) and OK-432 enhances the immune response by significantly increasing the production of interleukin-12 (IL-12) in splenocytes, particularly in the early stages after tumor inoculation.

This immune enhancement is primarily mediated by macrophages and suggests that the combination treatment may promote a type 1 T helper (Th1)-dominant immune response, which is beneficial for antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan enhances IL-12 production by OK-432-activated murine macrophages. Zhang, B., Fujimoto, T., Kaneda, A., et al.[2018]

The study aimed to evaluate the safety and efficacy of preoperative hypofractionated radiotherapy combined with capecitabine in patients with locally advanced rectal cancer, but it was discontinued due to high toxicity, with 38% of patients experiencing severe side effects.

Despite the treatment, no patients achieved a pathologically complete response, indicating that this regimen may not be effective and highlighting the need for further research to find safer alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer. Freedman, GM., Meropol, NJ., Sigurdson, ER., et al.[2022]

In a study comparing short-course radiotherapy followed by chemotherapy to conventional chemoradiotherapy in locally advanced rectal cancer, the pathological complete response (pCR) rate was similar between the two groups, with 6.7% in the study arm and 0% in the control arm, indicating comparable efficacy.

The short-course radiotherapy regimen significantly reduced acute toxicities (14.2% vs. 61.5% in the control arm) while maintaining similar rates of R0 resection (92.8% vs. 92.3%), suggesting better patient compliance and safety with the new treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Observational Study Comparing Long-Course Conventional Neoadjuvant Chemoradiotherapy with Short-Course Radiotherapy Followed by Consolidation Chemotherapy with Delayed Surgery in Locally Advanced Rectal Cancer. Thakur, N., Seam, RK., Gupta, MK., et al.[2020]

A review of 2217 adverse drug reaction reports related to immune checkpoint inhibitors (ICIs) from 2011 to 2018 revealed that these drugs, particularly nivolumab, are associated with a higher frequency of serious immune-related adverse events, including gastrointestinal and respiratory disorders.

Emerging safety signals, such as ischaemic heart disease and cardiac failure, were identified, indicating the need for further investigation into the long-term safety profile of ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. Cutroneo, PM., Isgrò, V., Ientile, V., et al.[2021]

In a study of 120 non-small-cell lung cancer patients undergoing chemotherapy, 80% experienced severe adverse drug reactions (ADRs), with 22.3% developing potentially life-threatening complications, leading to significant hospital stays and healthcare costs.

The average cost for managing toxicity per chemotherapy line was €3,366, with first-line treatments being more expensive than second-line, particularly due to ICU care associated with severe infections, highlighting the need for strategies to reduce these complications and their economic impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care--an observational analysis on non-small-cell lung cancer patients. Ihbe-Heffinger, A., Paessens, B., Berger, K., et al.[2022]

In a study of 108 patients with cT3-4 rectal cancer, preoperative intensity-modulated and image-guided radiotherapy (IMRT-IGRT) with a simultaneous integrated boost (SIB) achieved a high 5-year local control rate of 97%, indicating its effectiveness in managing the disease.

However, the treatment was associated with some late toxicity, with 9% of patients experiencing grade ≥3 gastrointestinal issues and 4% experiencing grade ≥3 urinary toxicity, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative intensity-modulated and image-guided radiotherapy with a simultaneous integrated boost in locally advanced rectal cancer: report on late toxicity and outcome. Engels, B., Platteaux, N., Van den Begin, R., et al.[2022]

Increasing the intensity of neoadjuvant therapy for rectal cancer, such as higher radiation doses or concurrent chemotherapy, may improve the rate of complete pathological responses, but careful patient selection is crucial for maximizing benefits.

Short-course radiotherapy (5 Gy × 5) is recommended for certain patients with T3 or N+ rectal cancer, while long-course chemoradiotherapy remains the standard for locally advanced cases, highlighting the need for individualized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy standard and progress in locally advanced rectal cancer]. Shen, L., Zhang, Z.[2018]

In a study of 141 patients with locally advanced rectal cancer, the use of a concomitant boost in radiotherapy during neoadjuvant treatment significantly improved overall survival rates, with 10-year overall survival at 52.9%.

The study found that factors such as female sex and having fewer than five positive lymph nodes were strong predictors of better overall and recurrence-free survival, highlighting the importance of patient characteristics in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Concomitant Radiation Boost in Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer. Badakhshi, H., Ismail, M., Boskos, C., et al.[2017]

In a study of 40 colorectal cancer patients who underwent potentially curative metastasectomy, those treated with modified FOLFOX6 (mFOLFOX6) showed a trend towards longer relapse-free survival (28.5 months) compared to those treated with oral fluoropyrimidines (14.8 months), although this was not statistically significant (p=0.11).

The overall survival rates were similar between the mFOLFOX6 group (37.9 months) and the fluoropyrimidine group (31.3 months), indicating that while mFOLFOX6 may help delay relapse, it does not significantly improve overall survival compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant chemotherapy comprising modified FOLFOX6 after curative resection of synchronous or metachronous metastasis from colorectal cancer]. Hatano, S., Ishibashi, K., Amano, K., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06600789

NCT06600789 | A Modular Phase 1/2 Study With CT7439 ... This study will initially evaluate CT7439 as a monotherapy in participants with locally advanced or metastatic solid malignancies, i.e., Module 1, ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/534555

A Modular Phase 1/2 Study with CT7439 in Participants ... This modular, multi-part, multi-arm, Phase 1/2, FIH study allows the evaluation of the safety and tolerability of CT7439, ...

3. trial.medpath.com trial.medpath.com/news/c2be6aeda35e216d/carrick-therapeutics-announces-first-patient-dosed-in-phase-1-clinical-trial-of-ct7439

Carrick Therapeutics Initiates Phase 1 Trial of Novel CDK12 ... The Phase 1 trial will assess the safety, pharmacokinetics, and early proof of principle of CT7439 in patients with advanced solid tumors. CT7439's dual ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e15722

Inhibition of transcriptional cyclin-dependent kinases ... These findings support further evaluation of the novel CDK12/13 inhibitor, CT7439, for the treatment of solid tumors with CDK12/13 upregulation.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2095177924002703

New insights into the dule roles CDK12 in human cancers Notably, two CDK12 inhibitors, dinaciclib and CT7439, have progressed to clinical trials for cancer therapy (Table 4). Despite these advances, challenges ...

6. carricktherapeutics.com carricktherapeutics.com/news-media/press-releases/detail/20/carrick-therapeutics-announces-u-s-fda-clearance-of-ind

Press Releases The US Food and Drug Administration (FDA) has cleared the Company's Investigational New Drug (IND) application for CT7439, a novel cyclin dependent kinase 12/ ...