First-in-human study evaluating the effect of various doses of ODM-212 in subjects with selected advanced solid tumours

Recruitment & Eligibility

Status: Ongoing

Sex: All

Target Recruitment: 213

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

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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