CP-506 / Convert Pharma - LARVOL DELTA

Phase 1/2 Clinical Trial of CP-506 (HAP) in Monotherapy or With Carboplatin or ICI (clinicaltrials.gov) - P1/2 | N=126 | Recruiting | Sponsor: Maastricht University Medical Center | Trial completion date: May 2026 ➔ May 2027 | Trial primary completion date: Feb 2026 ➔ Feb 2027

Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2

Harnessing hypoxia: CP-506's journey from bench to bedside in cancer therapy (EORTC-NCI-AACR 2024) - P1/2 | "CP-506 shows promise as a targeted therapeutic for solid tumours, leveraging selective activation in hypoxic regions to deliver cytotoxic effects. Its ability to induce a bystander effect and enhance immunotherapy efficacy suggests potential for combination approaches. The initiation of Phase I/IIa clinical evaluation (NCT04954599) underscores its clinical significance and paves the way for further investigation in cancer patients."

IO biomarker • Brain Cancer • Breast Cancer • CNS Tumor • Glioma • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer

Deficiencies in Homologous Recombination or the Fanconi Anemia Pathway Sensitize Tumors to the Novel Hypoxia-Activated Prodrug CP-506 (EACR 2024) - P1/2 | "CP-506-induced DNA damage in ex vivo tumors by γH2AX expression is currently being evaluated.Conclusion Deficiencies within HR and FA, but not NHEJ, enhanced the antitumor effects of CP-506. Therefore, DNA repair status in addition to tumor hypoxia is an important patient stratification factor to maximize the treatment benefit in the upcoming clinical trial of CP-506 (NCT04954599)."

Anemia • Hematological Disorders • Oncology • BRCA2 • ER • FANCD2

The Catalysis Mechanism of E. coli Nitroreductase A, a Candidate for Gene-Directed Prodrug Therapy: Potentiometric and Substrate Specificity Studies. (PubMed, Int J Mol Sci) - "Except for negative outliers nitracrine and SN-36506, the reactivity of ArNO2 increases with their electron affinity (single-electron reduction potential, E17) and is unaffected by their lipophilicity and Van der Waals volume up to 386 Å...Typically, the calculated hydride-transfer distances during ArNO2 reduction are smallwer than for Q. This explains the lower reactivity of quinones. Another factor that slows down the reduction is the presence of positively charged aliphatic substituents."

Journal • Oncology

Design and Biological Evaluation of Piperazine-Bearing Nitrobenzamide Hypoxia/GDEPT Prodrugs: The Discovery of CP-506. (PubMed, ACS Med Chem Lett) - "These prodrugs and their bromo/mesylate counterparts (25-27) were also evaluated for hypoxia-selective cell killing in vitro. These results in conjunction with stability assays recommended prodrug 26 (CP-506) for Phase I/II clinical trial."

Journal • Gene Therapies • Oncology

Overcoming radioresistance with the hypoxia-activated prodrug CP-506: a pre-clinical study of local tumour control probability. (PubMed, Radiother Oncol) - P1/2 | "The results support the use of CP-506 in combination with radiation in particular using hypofractionation schedules in hypoxic tumours. The magnitude of effect depends on the tumour model, therefore it is expected that applying appropriate patient stratification strategy will further enhance the benefit of CP-506 treatment for cancer patients. A phase I-IIA clinical trial of CP-506 in monotherapy or in combination with carboplatin or a checkpoint inhibitor has been approved (NCT04954599)."

Journal • Preclinical • Oncology

Phase 1/2 Clinical Trial of CP-506 (HAP) in Monotherapy or With Carboplatin or ICI (clinicaltrials.gov) - P1/2 | N=126 | Recruiting | Sponsor: Maastricht University | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Pan tumor • Breast Cancer • Hormone Receptor Breast Cancer • Immune Modulation • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2

"#ConvertPharmaceutical reported Three key academic publications on #CP506 https://t.co/WTlyqJrZYd" (@1stOncology)

Phase 1/2 Clinical Trial of CP-506 (HAP) in Monotherapy or With Carboplatin or ICI (clinicaltrials.gov) - P1/2 | N=126 | Not yet recruiting | Sponsor: Maastricht University | Trial completion date: Oct 2025 ➔ May 2026 | Trial primary completion date: Sep 2025 ➔ Feb 2026

Monotherapy • Pan tumor • Trial completion date • Trial primary completion date • Breast Cancer • Hormone Receptor Breast Cancer • Immune Modulation • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2

Phase 1/2 Clinical Trial of CP-506 (HAP) in Monotherapy or With Carboplatin or ICI (clinicaltrials.gov) - P1/2 | N=126 | Not yet recruiting | Sponsor: Maastricht University | Trial completion date: Oct 2024 ➔ Oct 2025 | Initiation date: Oct 2021 ➔ Jun 2022 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Monotherapy • Pan tumor • Trial completion date • Trial initiation date • Trial primary completion date • Breast Cancer • Hormone Receptor Breast Cancer • Immune Modulation • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2

Tissue Pharmacokinetic Properties and Bystander Potential of Hypoxia-Activated Prodrug CP-506 by Agent-Based Modelling. (PubMed, Front Pharmacol) - "In the present study, we investigate the pharmacological properties of the nitrogen mustard prodrug CP-506 in tumour tissues using in silico spatially-resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) modelling...Our simulations predict a striking bystander efficiency at tissue-like densities with the bis-chloro-mustard amine metabolite (CP-506M-Cl) identified as a major diffusible metabolite. Overall, this study shows that CP-506 has favourable pharmacological properties in tumour tissue and supports its ongoing development for use in the treatment of patients with advanced solid malignancies."

Journal • PK/PD data • Oncology • Solid Tumor

In Vivo Identification of Adducts from the New Hypoxia-Activated Prodrug CP-506 Using DNA Adductomics. (PubMed, Chem Res Toxicol) - "Eight adducts were detected in all xenograft models, and MDA-MB-231 showed the highest adduct levels. These results suggest that CP-506-DNA adducts can be used to better understand the mechanism of action and monitor the efficacy of CP-506 in vivo, as well as highlight a new role of DNA adductomics in supporting the clinical development of DNA-alkylating drugs."

Journal • Preclinical • Oncology • Solid Tumor

Selectively Targeting Tumor Hypoxia with the Hypoxia-Activated Prodrug CP-506. (PubMed, Mol Cancer Ther) - "Our results demonstrate that CP-506 selectively targets hypoxic tumor cells and has broad antitumor activity. Our data indicates that tumor hypoxia and cellular sensitivity to CP-506 are strong determinants of the antitumor effects of CP-506."

Journal • Oncology

Phase 1/2 Clinical Trial of CP-506 (HAP) in Monotherapy or With Carboplatin or ICI (clinicaltrials.gov) - P1/2; N=126; Not yet recruiting; Sponsor: Maastricht University

Clinical • Monotherapy • New P1/2 trial • Pan tumor • Immune Modulation • Oncology • Solid Tumor • BRCA1 • BRCA2

High-resolution/accurate-mass DNA adductomics to identify adducts formed by the hypoxia-activated alkylating agent, CP-506 and its metabolites (ACS-Fall 2019) - "Additionally, further efficacy and specificity analyses are being conducted on tumor biopsies obtained from animal models treated with CP-506. Future work will be focused on exploring these adducts’ potential as biomarkers of therapeutic potency, to be used to select the ideal target population for a precision, patient-oriented, and personalized chemotherapeutic approach."