Study of CT-01 as Monotherapy and Combination Therapy in Subjects With Intermediate or Advanced Hepatocellular Carcinoma

NCT06994572 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CT-01-CD-1
• Study Type: interventional
• Target: 141
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 1, open-label, multicenter, dose-escalation and dose-expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CT-01, administered either as monotherapy or in combination with everolimus. The study population includes subjects with intermediate or advanced hepatocellular carcinoma (HCC) who have progressed on, or are intolerant to, at least one prior line of systemic treatment. All available standard-of-care therapies should have been received, if deemed appropriate by the investigator (unless contraindicated or considered inappropriate by the treating physician). Eligible subjects are classified as Barcelona Clinic Liver Cancer (BCLC) stage B or C and must not be amenable to curative treatment approaches. Only subjects with preserved liver function (Child-Pugh Class A, score 5-6) at screening are eligible. Approximately 141 participants will be enrolled across 20 sites in Europe (France, Spain, and Germany).

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (4)

• Number of participants with treatment-emergent adverse events (TEAEs) during CT-01 monotherapy

  Safety and tolerability of CT-01 will be evaluated by monitoring the incidence of TEAEs, SAEs, AESIs, and TEAEs leading to study discontinuation or death. Unit of Measure: Number, nature, sverity and relation plausibility of AE

  Up to 12 months

• Maximum tolerated dose (MTDm) of CT-01 monotherapy

  The MTDm will be determined based on the incidence and type of dose-limiting toxicities (DLTs) during Cycle 1 of CT-01 monotherapy. Unit of Measure: mg/day

  Up to 12 months

• Number of participants with treatment-emergent adverse events (TEAEs) during CT-01 and everolimus combination therapy

  Safety and tolerability will be assessed through monitoring of TEAEs, SAEs, AESIs, and TEAEs leading to study discontinuation or death during combination therapy. Unit of Measure: Number, nature, sverity and relation plausibility of A

  Up to 12 months

• Maximum tolerated dose (MTDc) of CT-01 in combination with everolimus

  The MTDc will be determined based on the incidence of DLTs during Cycle 1 of the combination therapy. Unit of Measure: mg/day

  Up to 12 months

Secondary Outcomes (22)

• Objective response rate (ORR) per RECIST v1.1 and mRECIST for CT-01 monotherapy

  Up to 12 months

• Objective response rate (ORR) per RECIST v1.1 and mRECIST for CT-01 and everolimus

  Up to 12 months

• Maximum plasma concentration (Cmax)

  Up to 12 months

• Area under the concentration-time curve (AUC)

  Up to 12 months

• Time to maximum concentration (Tmax)

  Up to 12 months

Other Outcomes (6)

• Changes in ISR gene expression (ATF3, DDIT3) during CT-01 monotherapy

  Up to 12 months

• Association between PK/PD and anti-tumor activity during CT-01 monotherapy

  Up to 12 months

• Changes in GSPT1 and NEK7 protein levels during CT-01 and everolimus combination therapy

  Up to 12 months

Study Arms (4)

CT-01 PART 1A: Monotherapy - Dose Escalation

EXPERIMENTAL

Subjects receive CT-01 monotherapy at predefined dose levels. Doses assigned according to a dose-escalation protocol.

Drug: CT-01

CT-01 PART 1B: Monotherapy - Dose Expansion

EXPERIMENTAL

Subjects receive CT-01 monotherapy at the selected recommended dose level identified in Part 1A

Drug: CT-01

CT-01 PART 2A: Combotherapy - Dose Escalation

EXPERIMENTAL

Subjects receive CT-01 and everolimus orally once daily in 28-day cycles

Drug: CT-01; Drug: EVEROLIMUS

CT-01 PART 2B: Combotherapy - Dose Expansion

EXPERIMENTAL

Subjects receive CT-01 and everolimus at the recommended combination dose.

Drug: CT-01; Drug: EVEROLIMUS

Interventions

CT-01 DRUG

Investigational small-molecule degrader targeting transcription factors in HCC. Used as monotherapy or with everolimus in dose-escalation/expansion settings. Specific to protocol CT-01-CD-1.

CT-01 PART 1A: Monotherapy - Dose Escalation; CT-01 PART 1B: Monotherapy - Dose Expansion; CT-01 PART 2A: Combotherapy - Dose Escalation; CT-01 PART 2B: Combotherapy - Dose Expansion

EVEROLIMUS DRUG

Approved mTOR inhibitor used in combination with CT-01 for HCC in this study. Evaluated for safety, tolerability, and PK/PD in CT-01-CD-1 protocol.

CT-01 PART 2A: Combotherapy - Dose Escalation; CT-01 PART 2B: Combotherapy - Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
• Are ≥18 years of age and of any gender at the time of screening.
• Have confirmed histological and/or radiological diagnosis of HCC with a Child-Pugh Class A score of 5 to 6 points within 7 days of first dose of study drug.
• Has BCLC stage B and are ineligible for or are refractory to locoregional therapy and not amenable to a curative treatment approach, or BCLC stage C and are not amenable to a curative treatment approach.
• Have progressed on or are intolerant to ≥1 prior systemic standard of care treatment. All available standard of care treatments should have been received as prior systemic treatment if deemed appropriate by the investigator (unless such treatments are deemed contraindicated or inappropriate by the treating physician).
• Have Eastern Cooperative Oncology Group (ECOG) score ≤1.
• Have at least one measurable disease lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and/or modified RECIST (mRECIST), with a minimum of 1 target lesion in the liver at screening.
• Female subjects may be enrolled if they refrain from donating eggs (ova, oocytes) for the purpose of reproduction during the treatment period and for 6 months after the treatment period and if they are:
• Documented to be surgically sterile or postmenopausal, or
• Practicing true abstinence for at least 28 days prior to investigational medical product (IMP) administration and for 6 months after the treatment period and having a negative pregnancy test prior dosing, or
• Willing and able to comply with two forms of contraception methods, including one physical barrier (condom or diaphragm) plus another method, such as adequate hormonal method (eg, contraceptive implants, injectables, oral contraceptives) or nonhormonal methods (eg, intrauterine device, spermicidal) during and for 6 months after the treatment period and having a negative pregnancy test prior dosing. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male subjects with female partners of childbearing potential may be enrolled if they refrain from donating sperm during the treatment period and for 6 months after the last IMP administration and if they are:
• Documented to be surgically sterile (vasectomy), or
• Practicing true abstinence during the treatment period and for 6 months after the last IMP administration, or
• Willing and able to comply with two forms of contraception methods, including one physical barrier (condom or diaphragm) during the treatment period and for 6 months after the last IMP administration. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

You may not qualify if:

• Have not recovered from toxicities to baseline or Grade ≤1 by CTCAE version 5.0 from prior anticancer therapy, except alopecia and sub-optimally treated nausea, vomiting, or diarrhea.
• Have a history of liver transplant.
• Any other active malignancy at time of screening or diagnosis of another malignancy within 2 years before screening that requires active treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
• Have central nervous system (CNS) metastases or any other Grade \>2 CNS disorder. Subjects with CNS metastases who are stable on their treatment since a minimum of 4 weeks prior to screening are eligible.
• Have recent esophageal or gastric variceal bleeding within 4 weeks prior to screening. Subjects with treated, stable, or small varices without bleeding within the 4 weeks prior to screening are eligible.
• Have a history of symptomatic ascites requiring paracentesis within the past 3 months prior to screening.
• Have a prior diagnosis of rhabdomyolysis from any cause.
• Subjects with known retinal disease (eg, diabetic retinopathy, macular degeneration, retinal detachment/tear, etc).
• Have a history of clinically significant cytokine release syndrome as assessed by the treating physician, clinically significant hypotension (defined as a blood pressure \[BP\] consistently \<90/60 mmHg and/or a BP associated with symptoms of hypotension (dizziness, fainting, orthostatic hypotension \[systolic BP drop of \>20 mmHg or diastolic BP drop of \>10 mmHg on orthostasis\]), symptomatic hypocalcemia and/or a calcium level \<1.5 mmol/L.
• Have a history of pneumonitis or pericarditis.
• Subjects who are not, in the opinion of the investigator, willing or able to comply with the protocol or who present a contraindication to any study procedure.
• Have inadequate hematologic and end-organ function, defined as follows:
• Hemoglobin \<8.5 g/dL
• Absolute neutrophil count \<1,500 per mm3
• Platelet count \<75,000 per mm3

Sponsors & Collaborators

• Captor Therapeutics S.A.: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2025
• First Posted: May 29, 2025
• Study Start: May 26, 2025
• Primary Completion (Estimated): April 16, 2029
• Study Completion (Estimated): April 1, 2030
• Last Updated: May 29, 2025

Record last verified: 2025-05