NCT04954599

Phase 1/2 Clinical Trial of CP-506 (HAP) in Monotherapy or With Carboplatin or ICI

Phase 1/2 Modular Dose Escalation With Cohort Expansion of CP-506 (HAP) in Patients With Solid Tumor Types With High Incidence of HRD/FAD in Monotherapy or With Carboplatin or Patients With Solid Tumour and OPD Receiving ICI

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 126 (estimated)
• Sponsor: Maastricht University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A modular, first time in human, open label, multiple dose, accelerated escalation with cohort expansion study of the safety and pharmacokinetics of intravenous infusion of CP-506, a tumor agnostic Hypoxia Activated Prodrug in patients with HRD/FAD solid tumours or tumor types with high incidence of HRD/FAD in monotherapy or in combination with carboplatin or patients with solid tumour and oligoprogressive disease receiving immune checkpoint inhibitors (ICI): a phase I-IIa clinical trial

Detailed description

This study is a First in Human, early phase (I/IIa), 3 modules, 2 parts (A- dose escalation and B- cohort expansion), open-label, uncontrolled, multi-center, multiple dose, accelerated 3+3 dose escalation study. The study consist of 3 study modules. Module 1 is monotherapy with accelerated dose escalation. Modules 2 and 3 are also accelerated dose escalation modules, but with a combination of CP-506 with either Carboplatin or ICI. Initiation of modules 2 and 3 are dependent on the decision by the Independent Data Monitoring Committee (IDMC) based on the safety, tolerability and feasibility information from the study as a whole. Each study modules will consist of a Part A (dose finding) and an optional Part B (cohort expansion). The option to start Part B will be decided by the IDMC based on safety, tolerability and feasibility information from the study as a whole. The expansion cohorts will explore preliminary efficacy. Modules 2 and 3 will start after completion of module 1 and definition of the "minimal biological effective dose" (MBED) as the dose that results in 1) a decrease of 20% of hypoxia radiomics score on sequential CT of at least one lesion OR 2) a decrease of 20% of the initial tumour volume of at least one lesion. MBED is assessed by CT scan at visit 7, 12 and 13. After observation of an MBED in three patients, the data supporting the MBED assessment will be reviewed by the IDMC for confirmation. A maximum of 126 patients with advanced or metastatic cancer will be recruited in this study. * Module 1 - Monotherapy: up to 24 patients for Part A and 10 patients for Part B for whom no standard of care or known effective treatment options are available and with cancers that show a considerable incidence of Homologous Recombination or Fanconi Anaemia DNA repair defects (HRD/FAD) * Module 2 - Combination with Carboplatin: up to 24 patients for Part A and 22 patients for Part B for patients that receive carboplatin as standard of care: triple negative breast cancer and ovarian cancer. * Module 3 - Combination with ICI: up to 24 patients for Part A and 22 patients for Part B with advanced or metastatic cancer for whom standard of care immune checkpoint inhibitor (ICI) are currently administered for at least 6 months, would still be administered according to the treating clinician, outside any clinical trial but resulted in oligoprogression. The complete CP-506 therapy consists of three cycles of CP-506 treatment. Each treatment cycle consists of three consecutive days of IV infusion for two hours and one day for observation and blood sampling, and a recovery time of 3 weeks. Patients are expected to come to the hospital for 18 visits. They consist of 1 screening visit, 3 cycles of CP-506 treatment. Each cycle will be followed by a post cycle visit after 14 and 21 days. The follow up visit will take place at day 105.

Conditions

• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	CP-506	CP-506 is a hypoxia-activated DNA alkylating agent specifically designed to have a bystander effect, aqueous solubility, oral bioavailability, and no off-mechanism activation by the human aerobic reductase AKR1C3
DRUG	Carboplatin	Antineoplastic agent, ATC Code: LO1X A02
DRUG	Immune checkpoint inhibitor	Drug that blocks immune checkpoint proteins: PD-1, PD-L1, CTLA-4

Timeline

• Start date: 2023-05-30
• Primary completion: 2027-02-01
• Completion: 2027-05-01
• First posted: 2021-07-08
• Last updated: 2025-10-07

Locations

5 sites across 3 countries: Belgium, Netherlands, Spain