Neoplasms, benign, malignant and unspecified (including cysts and polyps) Cancer
Conditions
Interventions
This is an open-label study with ODM-212.
Part 1 is a dose escalation part. The anticipated maximum duration of the study for an individual subject is approximately 14 months including 1 year (365 da
Sponsors
Orion Corporation (Finland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects =18 years old 2. Subjects must have histological diagnosis of local advanced or metastatic solid tumour with available local data for loss-of-function genetic alterations in NF2/LATS1/LATS2, or YAP/TAZ fusions Part 2 of the CT: Any solid tumour type potentially harbouring a Hippo pathway alteration and, therefore, potentially responsive to TEAD inhibition based on data from Part 1 or other existing or emerging scientific data 3. Subjects must be in need of systemic treatment for their cancer and to either be refractory to or have progressed on, are intolerant to, or are not otherwise a candidate, in the opinion of the investigator, for any of the currently available established therapies 4. Part 2 of the CT only: Subjects must have measurable disease by response evaluation criteria in solid tumours (RECIST v. 1.1 or modified RECIST for MPM) 5. Part 2 of the CT only: A fresh or recent (taken up to 1 year ago) primary tumour tissue sample from a diagnostic biopsy/surgery or a tumour biopsy taken from a metastasis must be available; exemptions possible by the sponsor’s decision 6. Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale 7. Life expectancy of >12 weeks 8. Willing and able to comply with all aspects of the protocol 9. Provide written informed consent (or witness consent) prior to any study-specific screening procedures
Exclusion criteria
Exclusion criteria: 1. Other malignancy active within the previous 2 years except for basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast, for which the subject has completed curative therapy. 2. Prior chemotherapy, immunotherapy (tumour vaccine, cytokine or growth factor given to control the cancer) or other anti-cancer therapy within less than 2 weeks before study drug administration, or any persistent unresolved toxicity from such previous therapy that, according to the judgement of the investigator, may pose a risk for the subject if taking part in the study. 3. Prior definitive radiation therapy within less than 4 weeks and prior palliative radiotherapy within less than 2 weeks before study drug administration. Radiopharmaceuticals (strontium, samarium) within less than 8 weeks before study drug administration. 4. Subjects with brain or subdural metastases are not eligible unless the metastases are asymptomatic and do not require treatment or have been adequately treated with local therapy. Confirmation of radiographic stability must be done by comparing the brain scan (CT or MRI) performed during the screening period to a brain scan performed at least 4 weeks earlier (and following local therapy where applicable) using the same imaging modality as during the screening period. It is not the intention of this protocol to treat subjects with active brain metastasis. 5. Known human immunodeficiency virus (HIV) infection 6. Active infection requiring therapy, including known positive tests for Hepatitis B surface antigen and hepatitis C virus (HCV) RNA. Pre-study testing for these pathogens is not required. 7. Major surgery within 4 weeks before the first dose of the study drug or minor surgery within 1 week (subject must also have recovered from any surgery-related toxicities to less than CTCAE Grade 2). 8. Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses >10 mg/day prednisone or equivalent) within 2 weeks before study drug administration. 9. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g. nausea, diarrhoea, or vomiting) that might impair the bioavailability of ODM-212. 10. Use of other IMPs within 2 weeks or at least 5 half-lives (whichever is longer) before stud drug administration, or any persistent unresolved toxicity from such treatment that, according to the judgement of the investigator, may pose a health risk for the subject, if taking part in the study. For drugs such as investigational monoclonal antibodies with half-lives >10 days, at least 8 weeks is required. In addition, all visits (apart from survival follow-up) related to the use of another IMP must be completed before dosing with ODM-212 may commence 11. Use of any live or live-attenuated vaccines (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) within 28 days prior to the first dose of study drug.) 12. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250 ms, a prolonged QTcF/B interval (QTc >470 ms) as demonstrated by repeated ECG at screening, performed according to local practice. A history of risk factors for torsade de pointes (e.g. heart failure, hypokalaemia, family history of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 and 2: 1. Incidence, frequency, and severity of treatment-emergent adverse events (TEAEs): adverse events will be recorded from the start of treatment administration until 28 days 2. Other general safety assessments: laboratory tests, physical examination findings, body temperature, systolic and diastolic blood pressure, 12-lead ECGs including heart rate will be assessed per protocol schedule | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: 1. MTD defined using DLTs evaluated during the first 21 days of treatment of each patient in Part 1. According to Bayesian Optimal Interval (BOIN) this is the dose for which the estimated toxicity rate (the rate of DLTs) is closest to the target toxicity rate of 25%. A DLT is defined as an event related to ODM-212 as judged by the investigator and/or the SMB, occurring during the DLT period and leading to treatment discontinuation at the current dose level 2. Dose selection based on MTD, DLT, TEAEs, clinical and laboratory assessments. The dose will be selected at the end of Part 1 before starting Part 2. Data will be evaluated after each cohort. 3. ODM-212 concentrations and PK variables evaluated using plasma samples are collected at multiple timepoints during Day 1 and Day 15 and prior to dosing on all at other visit days in accordance with the protocol schedule (Day 1: AUCt, AUC0-12, AUC0-24, AUC8, 1z, Vz/F, Cl /F, t1/2, Cmax, Tmax; Day 15: AUCt, AUC0-12, AUC8, 1z, t1/2, Cmax, Cav, Tmax, Rac,obs). Part 1 of the CT: Antitumour activity assessed using CT or MRI images taken every 8 weeks for the first 52 24 weeks and every 12 weeks thereafter. The images are evaluated according to the RECIST criteria to assess the antitumour activity based on: clinical benefit rate (CBR) at week 8, as best response of either complete response (CR), partial response (PR), or stable disease (SD) at week 8. CBR, as best response of either CR, PR, or at least 8 weeks of SD. Objective response rate (ORR) as response of either CR or PR. Both defined clinical benefit rates and ORR will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 (modified RECIST for MPM, as assessed by the investigator. In addition, the investigator will assess the Eastern Cooperative Oncology Group (ECOG) performance status at every visit to assess the antitumour activity based on change from baseline. Part 2: 1. PFS will be assessed by the investigator according to RE | — |
Countries
England, Finland, France, Spain, Switzerland, United Kingdom
Outcome results
None listed