Safety and Pharmacokinetics of ODM-208 in Patients With Metastatic Castration-resistant Prostate Cancer

Conditions

Prostate Cancer Metastatic

Brief summary

The purpose of this first-in-man study is to evaluate safety and tolerability of ODM-208 in patients with metastatic castration-resistant prostate cancer.

Detailed description

Safety and tolerability profile of ODM-208 will be explored

Karim Fizazi, Guilhem Roubaud, Alice Bernard‐Tessier, Gwénaëlle Gravis, Aude Fléchon et al. (20 authors)

Journal of Clinical Oncology2024-01-294 citations

10.1200/jco.2024.42.4_suppl.159

Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer

Karim Fizazi, Alice Bernard‐Tessier, Guilhem Roubaud, Tapio Utriainen, Philippe Barthélémy et al. (20 authors)

NEJM Evidence2023-12-2622 citations

10.1056/evidoa2300171

Androgen receptor (AR) mutations in men with metastatic castration-resistant prostate cancer (mCRPC): Incidence and natural history.

Alice Bernard‐Tessier, Guillaume Mulier, Paula Nay, Capucine Baldini, Laurence Albigès et al. (14 authors)

Journal of Clinical Oncology2023-02-206 citations

10.1200/jco.2023.41.6_suppl.221

Impact of activating androgen receptor (AR) mutations on AR sensitivity to alternative ligands and response to ODM-208, a selective, first-in-class CYP11A1 inhibitor, in patients with advanced metastatic castration-resistant prostate cancer (mCRPC).

Alice Bernard‐Tessier, Tapio Utriainen, Natalie Cook, Philippe Barthélémy, Nada Lallous et al. (11 authors)

Journal of Clinical Oncology2022-06-015 citations

10.1200/jco.2022.40.16_suppl.5057

Phase 1 results of the ODM-208 first-in-human phase 1-2 trial in patients with metastatic castration-resistant prostate cancer (CYPIDES).

Karim Fizazi, Natalie Cook, Philippe Barthélémy, Alice Bernard‐Tessier, Capucine Baldini et al. (14 authors)

Journal of Clinical Oncology2022-02-169 citations

10.1200/jco.2022.40.6_suppl.018

Abstract 1250: ODM-208, a novel, small-molecule CYP11A1 inhibitor, demonstrates strong inhibition of steroid biosynthesis and antitumor activity in castration-resistant prostate cancer (CRPC) model

Mari Karimaa, Henna Kettunen, Meri Ramela, Suvi Mansikka-Savolainen, Marcin Chruściel et al. (12 authors)

Cancer Research2021-07-01

10.1158/1538-7445.am2021-1250

Interventions

DRUGODM-208

co-administered with glucocorticoid and fludrocortisone, orally daily

DRUGMidazolam

orally

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

Main Inclusion Criteria: * Written informed consent (IC) obtained. * Male aged ≥ 18 years. * Histologically confirmed adenocarcinoma of the prostate. * Castration resistant prostate cancer with serum testosterone \< 50 ng/dl. * Metastatic disease. * Ongoing androgen deprivation therapy with GnRH analogue or antagonist, or have had bilateral orchiectomy. * Received at least one prior line of novel hormonal androgen receptor (AR) targeted therapy (e.g. abiraterone, enzalutamide). * ECOG performance status 0-1. * Adequate marrow, liver and kidney function. * Able to swallow study treatment. * Part 1: Treatment with at least 1 line of chemotherapy or ineligibility for chemotherapy. Part 2: Treatment with at least 1 line of taxane-based chemotherapy in castration-sensitive prostate cancer (CSPC) or in CRPC. Main

Exclusion criteria

* History of pituitary or adrenal dysfunction. * Known brain metastases or active leptomeningeal disease. * Active infection or other medical condition that would make corticosteroid contraindicated. * Poorly controlled diabetes. * Hypotension or uncontrolled hypertension. * Clinically significantly abnormal serum potassium or sodium level. * Active or unstable cardio/cerebro-vascular disease including thromboembolic events. * Prolonged QTcF interval.

Design outcomes

Primary

Measure	Time frame	Description
Maximum tolerated dose (MTD)	Within first 28 days of treatment	Highest dose level at which under 33% of patients in a cohort experience DLT

Countries

Finland, France, United Kingdom, United States

Contacts

PRINCIPAL_INVESTIGATORKarim Fizazi

Gustave Roussy, Cancer Campus, Grand Paris

Outcome results

None listed