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

Approved 06/09/2023, London Central REC (Health Research Authority, HRA RES Centre Manchester, Floor 3, 3 Piccadilly Place, London Road, Manchester, M1 3BN, United Kingdom; +44 (0)207 104 8225, +44 (0)207 104 8077, +44 (0)207 104 8258; londoncentral.rec@hra.nhs.uk), ref: 23/LO/0644

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

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, AUC∞, 1z, Vz/F, Cl /F, t1/2, Cmax, Tmax; Day 15: AUCt, AUC0-12, AUC∞, 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 RECIST v.1.1 (modified RECIST for MPM). Imaging is performed once every 8 weeks until week 24 and thereafter every 12 weeks.
2. ECOG performance status, CBR, duration of objective response, clinical disease progression. ECOG performance status is assessed at every visit. CBR is measured via RECIST at all imaging visits - see above.

Part 1 and 2:
1. OS will be assessed throughout the study and a survival sweep will be performed 1 year after Last Subject Last Visit (LSLV)
2. ORR i.e. the rate of CR and/or PR by the investigator according to RECIST v. 1.1 (modified RECIST for MPM). Imaging is performed once every 8 weeks until week 24 and thereafter every 12 weeks.
3. The rate of clinical benefit defined as: as best response of CR and/or PR and/or SD at week 8; as best response of CR and/or PR and/or at least 8 weeks of SD by RECIST v. 1.1 (modified RECIST for MPM).