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

NCT04954599 | Recruiting Phase 1 DMC

• 3 other identifiers: TUMAGNOSTIC(CP506-001)2021-000423-12694812
• Study Type: interventional
• Target: 126
• Locations: 3 countries
• Sites: 5

Brief 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

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

Homologous recombination DNA repair defects; Fanconi Anaemia DNA repair defects; Triple negative breast cancer; Ovarian cancer; Prostate cancer; Pancreatic cancer; Head and neck cancer; Hypoxia Activated Prodrug; Alkylating Agents; Carboplatin; Immune Checkpoint Inhibitor

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-emergent adverse events including dose-limiting toxicities

  The proportion of patients with treatment-emergent (serious) adverse events including dose-limiting toxicity (DLT)

  Baseline until 60 days after last administration of CP-506

• Incidence of clinically significant abnormal measurements in physical examination, vital signs, electrocardiogram (ECG), lab tests and ECOG performance status

  Physical examination; vital signs; electrocardiogram (ECG); haematology; clinical chemistry; urinalysis; plasma/renal makers; tumour markers; ECOG performance status

  Baseline until 60 days after last administration of CP-506

Secondary Outcomes (4)

• Area under curve of CP-506 plasma concentration

  At the end of cycle 1 day 4

• Determine the minimal biological effective dose

  Baseline until 60 days after last administration of CP-506

• Objective Response Rate

  Baseline until 60 days after last administration of CP-506

• Percentage change in tumour size

  Baseline until 60 days after last administration of CP-506

Study Arms (6)

Module 1A Monotherapy Multiple Ascending Dose

EXPERIMENTAL

Multiple ascending dose cohorts dosing CP-506 monotherapy in all patients up to a maximally tolerated or maximally feasible dose Intervention: Drug: CP-506

Drug: CP-506

Module 1B Monotherapy Dose Expansion Cohort

EXPERIMENTAL

Expansion cohort dosing CP-506 monotherapy in patients at recommended phase 2 dose (RP2D) Intervention: Drug: CP-506

Drug: CP-506

Module 2A Combination with carboplatin Multiple Ascending Dose

EXPERIMENTAL

Multiple ascending dose cohorts dosing CP-506 in combination with carboplatin in all patients up to a maximally tolerated or maximally feasible dose Intervention: Drug: CP-506

Drug: CP-506; Drug: Carboplatin

Module 2B Combination with carboplatin Dose Expansion Cohort

EXPERIMENTAL

Expansion cohort dosing CP-506 in combination with carboplatin in patients at recommended phase 2 dose (RP2D) Intervention: Drug: CP-506

Drug: CP-506; Drug: Carboplatin

Module 3A Combination with Immune Checkpoint Inhibitor Multiple Ascending Dose

EXPERIMENTAL

Multiple ascending dose cohorts dosing CP-506 in combination with Immune Checkpoint Inhibitor in all patients up to a maximally tolerated or maximally feasible dose Intervention: Drug: CP-506

Drug: CP-506; Drug: Immune checkpoint inhibitor

Module 3B Combination with carboplatin Dose Expansion Cohort

EXPERIMENTAL

Expansion cohort dosing CP-506 in combination with Immune Checkpoint Inhibitor in patients at recommended phase 2 dose (RP2D) Intervention: Drug: CP-506

Drug: CP-506; Drug: Immune checkpoint inhibitor

Interventions

CP-506 DRUG

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

Also known as: HAP CP-506

Module 1A Monotherapy Multiple Ascending Dose; Module 1B Monotherapy Dose Expansion Cohort; Module 2A Combination with carboplatin Multiple Ascending Dose; Module 2B Combination with carboplatin Dose Expansion Cohort; Module 3A Combination with Immune Checkpoint Inhibitor Multiple Ascending Dose; Module 3B Combination with carboplatin Dose Expansion Cohort

Carboplatin DRUG

Antineoplastic agent, ATC Code: LO1X A02

Also known as: Paraplatin

Module 2A Combination with carboplatin Multiple Ascending Dose; Module 2B Combination with carboplatin Dose Expansion Cohort

Immune checkpoint inhibitor DRUG

Drug that blocks immune checkpoint proteins: PD-1, PD-L1, CTLA-4

Also known as: Ipilimumab, Nivolumab, Pembrolizumab, Atezolizumab, Avelumab, Durvalumab, Cemiplimab

Module 3A Combination with Immune Checkpoint Inhibitor Multiple Ascending Dose; Module 3B Combination with carboplatin Dose Expansion Cohort

Eligibility Criteria

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

You may qualify if:

• Male or female, aged 18 years or more at the time of signing the informed consent
• Be willing and able to provide written informed consent for the trial
• Life expectancy of at least 3 months
• Be willing to have a biopsy collection procedure
• ECOG Performance status \<= 2
• Must have adequate organ and bone marrow function, defined as the following:
• ANC ≥ 1500 µL 6.2. Hemoglobin ≥ 9.0 g/dL 6.3. Platelets ≥ 100 000 µL 6.4. Total bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \>1.5 × ULN 6.5. AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN (≤ 5 × ULN for participants with liver metastases) 6.6. Creatinine ≤ 1.5 × ULN 6.7. Coagulation: INR ≤ 1.5 × ULN (or within therapeutic ranges for participants on anticoagulant treatment)
• Measurable disease on CT scan (RECIST 1.1)
• If female, not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) 8.2. A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 4 weeks after the last dose of study treatment and shows a negative pregnancy test before the start of the treatment
• If male, must agree to use contraception during the treatment period and for at least 4 weeks after the last dose of study treatment
• Able and willing to comply with the protocol Module 1 - monotherapy
• Have histologically or cytologically-confirmed advanced or metastatic solid tumour for whom no standard of care or known effective treatment options are available
• Have indications of Homologous Recombination (HR) or Fanconi Anaemia (FA) DNA damage repair defects, based on hereditary cancer diagnostics (e.g. BRCA1/2 carriers), dedicated HRD genomic assays (including exome-sequencing) from liquid or tissue biopsies. Presence of such a defect must have been established via a tissue based next generation sequencing test, performed --in a CAP/CLIAcertified (or comparable local or regional certification) laboratory, or via a germline test from one of the following approved providers: Myriad Genetics; Invitae; Ambry; Quest; Color Genomics; MSKCC-IMPACT; GeneDx; Foundation Medicine OR Have cancers with an increased incidence of HRD/FAD: ovarian (41%), breast (18%), pancreas (10%), prostate (9%), and head and neck (5%) OR Patients who were previously responsive to alkylating agent (Partial Response/Complete Response according to RECIST criteria).
• Module 2 - Carboplatin combination

You may not qualify if:

• Core:
• Prior radiotherapy to more than 25% of bone marrow
• Not recovered from all acute toxic effects of prior anticancer therapy (excluding CTCAE Grade 1 alopecia or peripheral neuropathy)
• Patients with significant cardiac co-morbidity, such as NYHA Class III or IV CHF, unstable angina, MI within the previous 6 months, or ventricular arrhythmias requiring drug therapy, pacemaker or implanted defibrillator. Serious, uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third-degree atrioventricular block. This does not apply to patient with a pace maker. Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting or bypass grafting. Congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system. Symptomatic pericarditis
• A marked baseline prolongation of QT/QTc interval (\> 450 ms)
• History of risk factors for Torsade de Pointe (e.g. heart failure, hypokalemia, family history of Long QT syndrome)
• Use of concomitant medication prolonging the QT/QTc interval
• Evidence of uncontrolled infection or infection requiring a concomitant parenteral antibiotic
• Evidence of any other significant clinical disorder or laboratory finding that in the opinion of the Investigator may compromise patient safety during study participation.
• Patients with a diagnosis (or strong suspicion) of a rare genetic disorder related to germline biallelic HR/FA and DNA repair gene mutations, such as Fanconi anemia patients of any subtype, Ataxia telangiectasia, Xeroderma pigmentosum, Cockayne, Nijmegen breakage, Werner and Bloom syndrome patients
• Patient or physician plans concomitant chemotherapy, radiation therapy, hormonal and/or biological treatment for cancer including immunotherapy while on study
• Patient has been treated with any investigational drug or investigational therapeutic device within 30 days (60 days in case of biological compound) of initiating study treatment
• Less than 4 weeks since prior major surgery
• Known positive for HIV, Hepatitis B surface antigen positive or Hepatitis C positive with abnormal liver function tests
• Known allergy to alkylating agents

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Erasmus Medical Center: collaborator
• Jules Bordet Institute: collaborator
• Academisch Ziekenhuis Maastricht: collaborator
• Vall d'Hebron Institute of Oncology: collaborator
• University Ghent: collaborator

Study Sites (5)

Institut Jules Bordet

Brussels, Belgium

NOT YET RECRUITING

UZ Gent

Ghent, 9000, Belgium

NOT YET RECRUITING

Academisch Ziekenhuis Maastricht (Leading Centre)

Maastricht, Limburg, 6229HX, Netherlands

RECRUITING

Erasmus MC

Rotterdam, Netherlands

RECRUITING

Institut Vall d'Hebron

Barcelona, 08035, Spain

NOT YET RECRUITING

Related Publications (5)

• Fu Z, Mowday AM, Smaill JB, Hermans IF, Patterson AV. Tumour Hypoxia-Mediated Immunosuppression: Mechanisms and Therapeutic Approaches to Improve Cancer Immunotherapy. Cells. 2021 Apr 24;10(5):1006. doi: 10.3390/cells10051006.

  PMID: 33923305 BACKGROUND

• van der Wiel AMA, Jackson-Patel V, Niemans R, Yaromina A, Liu E, Marcus D, Mowday AM, Lieuwes NG, Biemans R, Lin X, Fu Z, Kumara S, Jochems A, Ashoorzadeh A, Anderson RF, Hicks KO, Bull MR, Abbattista MR, Guise CP, Deschoemaeker S, Thiolloy S, Heyerick A, Solivio MJ, Balbo S, Smaill JB, Theys J, Dubois LJ, Patterson AV, Lambin P. Selectively Targeting Tumor Hypoxia With the Hypoxia-Activated Prodrug CP-506. Mol Cancer Ther. 2021 Dec;20(12):2372-2383. doi: 10.1158/1535-7163.MCT-21-0406. Epub 2021 Oct 8.

  PMID: 34625504 BACKGROUND

• Solivio MJ, Stornetta A, Gilissen J, Villalta PW, Deschoemaeker S, Heyerick A, Dubois L, Balbo S. In Vivo Identification of Adducts from the New Hypoxia-Activated Prodrug CP-506 Using DNA Adductomics. Chem Res Toxicol. 2022 Feb 21;35(2):275-282. doi: 10.1021/acs.chemrestox.1c00329. Epub 2022 Jan 20.

  PMID: 35050609 BACKGROUND

• Jackson-Patel V, Liu E, Bull MR, Ashoorzadeh A, Bogle G, Wolfram A, Hicks KO, Smaill JB, Patterson AV. Tissue Pharmacokinetic Properties and Bystander Potential of Hypoxia-Activated Prodrug CP-506 by Agent-Based Modelling. Front Pharmacol. 2022 Feb 8;13:803602. doi: 10.3389/fphar.2022.803602. eCollection 2022.

  PMID: 35211015 BACKGROUND

• Yaromina A, Koi L, Schuitmaker L, van der Wiel AMA, Dubois LJ, Krause M, Lambin P. Overcoming radioresistance with the hypoxia-activated prodrug CP-506: A pre-clinical study of local tumour control probability. Radiother Oncol. 2023 Sep;186:109738. doi: 10.1016/j.radonc.2023.109738. Epub 2023 Jun 12.

  PMID: 37315579 DERIVED

Related Links

• Holder of CP-506 IP
• Video of mechanism of action

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Ovarian Neoplasms; Prostatic Neoplasms; Pancreatic Neoplasms; Head and Neck Neoplasms

Interventions

Carboplatin; Immune Checkpoint Inhibitors; Ipilimumab; Nivolumab; pembrolizumab; atezolizumab; avelumab; durvalumab; cemiplimab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Loes Jansen, MD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

• Henk Verheul, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Nuria Kotecki, MD, PhD

  Jules Bordet Institute

  PRINCIPAL INVESTIGATOR

• Sylvie Rottey, MD, PhD

  UZ Gent

  PRINCIPAL INVESTIGATOR

• Irene Brana, MD, PhD

  Institut Vall d'Hebron

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ludwig Dubois, PhD

CONTACT

+31433882909; ludwig.dubois@maastrichtuniversity.nl

Study Design

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

Model Details: A modular, multi-arm, multi-part, first time in patient study

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: July 8, 2021
• Study Start: May 30, 2023
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: October 7, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); BE (2); NL (2)