Phase 1/2 Study of ODM-212 Plus Anti-Cancer Therapy in Patients With Advanced Solid Tumours: Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy
- Trial ID
- 2025-524620-22-00
- Protocol
- 3134003
- Sponsor
- Orion Corporation
Trial statistics
Objectives
The primary objective is to evaluate the safety and tolerability of ODM-212 in combination with anti-cancer therapy in participants with selected advanced solid tumours. In part 1, this assessment is used to determine the recommended dose for part 2, which is clinically relevant for dose selection and subsequent development. The secondary objectives are to evaluate preliminary anti-tumour activity, to characterise the pharmacokinetics of ODM-212 in combination with anti-cancer therapy, to further evaluate preliminary anti-tumour activity in part 2, to define the optimal dose(s) for further clinical trials, and to further characterise pharmacokinetics in part 2.
Participants
The trial population comprised 68 participants with histologically or cytologically confirmed advanced or metastatic, unresectable solid tumours. Both male and female adults were included, with an age of at least 18 years. Participants were required to have an ECOG performance status of 0-1, an estimated life expectancy of more than 12 weeks, and the ability to take oral medication and record daily adherence. The population was selected from individuals willing and able to comply with the protocol and receive one of the anti-cancer therapies studied. Relevant inclusion requirements also included informed consent, availability for paired fresh tumour biopsy, and recent representative tumour tissue; in Part 2, measurable disease by RECIST v. 1.1 was required. No information on diet, physical activity, or other lifestyle considerations was provided.
Plans and Procedures
This is a phase 1/2, open-label trial evaluating ODM-212 in combination with anti-cancer therapy in participants with selected advanced solid tumours. The study is divided into two parts. Part 1 is used to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy, and to determine the recommended dose for Part 2. Part 2 further evaluates safety and tolerability at the selected dose. The overall trial duration is estimated from 2026-05-20 to 2029-12-30. Trial procedures include a screening visit to confirm eligibility, obtain informed consent, review medical history and study criteria, and collect required tumour tissue and paired fresh tumour biopsies when applicable. On-treatment visits are performed to assess treatment administration, adverse events, laboratory values, electrocardiograms, pharmacokinetics, and disease response. Follow-up visits are conducted after treatment to monitor ongoing safety and outcomes. An end-of-study visit is performed to complete final assessments. Participant involvement is expected to continue for the duration of treatment and scheduled follow-up. Early termination may occur because of disease progression, unacceptable toxicity, withdrawal of consent, protocol non-compliance, investigator decision, or other circumstances requiring discontinuation.
Treatment
ODM-212 was administered orally as coated tablets in 5 mg and 40 mg strengths. The trial evaluated ODM-212 in combination with anti-cancer therapy in participants with advanced solid tumours. No dose, dosing frequency, or specific administration schedule was provided in the source data.
Paclitaxel albumin-bound, nivolumab, gemcitabine, ipilimumab, and sotorasib were administered as the non-experimental anti-cancer therapies in the study. Paclitaxel albumin-bound, nivolumab, gemcitabine, and ipilimumab were given by intravenous administration, while sotorasib was administered orally. The source data did not specify the pharmaceutical form, dose, dosing frequency, or administration schedule for these treatments.
Efficacy
Efficacy will be assessed by objective response rate, duration of response, disease control rate, progression-free survival, and duration of stable disease in Part 1. In Part 2, efficacy will be assessed by objective response rate, duration of response, disease control rate, clinical benefit rate, progression-free survival, and overall survival. These efficacy evaluations will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Provide written informed consent (IC; or witness consent) prior to any trial-specific screening procedures.
- Willing and able to comply with all aspects of the protocol.
- Male or female participants ≥18 years old.
- Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- Life expectancy of >12 weeks, in the opinion of the investigator.
- Ability to take oral medications and willing to record daily adherence to investigational product.
- Participants with histologically or cytologically confirmed advanced or metastatic, unresectable solid tumours and who are able and willing to receive one of the anti-cancer therapies studied in this trial according to the investigator
- Part 2 only: Participants must have measurable disease by response evaluation criteria in solid tumours (RECIST) v. 1.1
- A recent (taken up to 1 year ago), representative tumour tissue sample (from primary tumour or from metastasis) must be available. Tissue must be a core needle biopsy, excisional or incisional biopsy. Biopsies of bone lesions that do not have a soft tissue component or decalcified bone tumour samples are also not acceptable. Exemptions possible by the sponsor’s decision
- Amenable for paired fresh tumour biopsy at screening period and on-treatment. Exemptions possible by the sponsor’s decision.
Exclusion Criteria
- 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 participants have completed curative therapy.
- Prior anti-cancer therapy within less than 2 weeks before trial treatment administration.
- Any persistent unresolved toxicity from previous anti-cancer therapies of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 (except for peripheral neuropathy, alopecia, endocrine disorders that are controlled with replacement hormone therapy and asymptomatic laboratory abnormalities). Ongoing adjuvant treatments for previous cancers are allowed as concomitant treatments if they do not have direct anti-tumour effect on the index tumour (e.g. hormone-suppressing agents).
- Prior definitive radiation therapy within less than 4 weeks and prior palliative radiotherapy within less than 2 weeks before trial treatment administration. Radiopharmaceuticals should be expected to have cleared sufficiently from the participant’s body before trial treatment administration.
- Participants with brain or subdural metastases are not eligible, unless the metastases are asymptomatic and have been adequately treated with local therapy.
- Any severe active infection within 1 week of trial enrolment.
- Known positive tests for hepatitis B surface antigen or hepatitis C virus (HCV) RNA; known human immunodeficiency virus (HIV) infection. Screening test is not required unless participant has clinical findings suggestive of HIV, hepatitis B virus (HBV) or HCV infection.
- Major surgery within 4 weeks before the first dose of trial treatment or minor surgery within 1 week (participant must also have recovered from any surgery-related toxicities to less than CTCAE Grade 2).
- Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses >10 mg/day prednisone or equivalent) within 2 days before trial treatment administration.
- 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
- Use of other investigational medicinal products within 2 weeks or at least 5 half-lives (whichever is longer) before trial treatment administration, or any persistent unresolved toxicity from such treatment that, according to the judgement of the investigator, may pose a health risk for the participant, if taking part in the trial. 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 investigational medicinal product must be completed before dosing with trial treatments may commence.
- Use of any live or live-attenuated vaccines (e.g., intranasal influenza, measles, mumps, rubella, shingles, oral polio, Bacillus Calmette–Guérin [BCG], yellow fever, varicella, and TY21a typhoid vaccines) within 28 days prior to the first dose of study drug.
- 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 QTc interval (QTcF/B >470 ms) as demonstrated by 2 out of 3 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 long QT Syndrome) or the use of drugs that prolong the QT interval and are clearly associated with a known risk of torsade de pointes, even when taken as recommended per Crediblemeds.org QTdrugs list.
- Significant cardiovascular impairment: history of congestive heart failure of New York Heart Association (NYHA) Class III-IV, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke, left ventricular ejection fraction (LVEF) <50%, cardiac arrhythmia requiring medical treatment (including oral anticoagulation) within 6 months prior to the first dose of trial treatment.
- Female participants who are breastfeeding or pregnant at screening or baseline. A separate baseline assessment for pregnancy is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
- Female participants of childbearing potential who meet any of the following criteria: - Had unprotected sexual intercourse within 30 days before study entry or who do not agree to use a highly effective method of contraception throughout the entire treatment period and for time periods specified in the protocol after treatment discontinuation. Highly effective contraception methods are specified in the protocol. - Are neither using a highly effective method of contraception as listed in the protocol nor currently abstinent or do not agree to refrain from sexual activity during the treatment period and for the time periods listed in the protocol after treatment discontinuation. - Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive combined with a barrier method (preferably male condom) during the trial and for the time periods listed in the protocol after treatment discontinuation. - NOTE: All female participants will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilised surgically (i.e. total hysterectomy or bilateral oophorectomy, with surgery at least 1 month before dosing).
- Male participants who are unwilling to practice acceptable methods of birth control during treatment and for periods specified in the protocol after treatment discontinuation, with partners who are women of childbearing potential (WOCBP); in addition no sperm donation is allowed during the treatment periods and periods specified in the protocol following treatment discontinuation. Acceptable methods of birth control for men are specified in the protocol; in addition, partners who are WOCBP must use at least one form of highly effective contraception as listed in exclusion criteria 16 in the protocol.
- At least moderately impaired kidney function (estimated glomerular filtration rate [eGFR] <60 ml/min), calculated as follows: eGFR(ml/min) = eGFR (ml/min/1.73m2) x [BSA(m2):1.73] where the body surface area (BSA) is calculated using e.g. the Mosteller formula: BSA=√[(Height (cm)× Weight(kg)) / 3600]
- Hepatic impairment defined as having any of the following laboratory values at screening: total bilirubin ≥1.5xupper limit of normal (ULN) (or >3xULN for participants with Gilbert’s syndrome), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3xULN (or >5xULN for participants with liver metastasis), or albumin ≤25 g/l.
- Abnormalities in coagulation values defined as international normalised ratio (INR) >1.5xULN at screening (unless participant is receiving anticoagulant therapy, as long as participant’s laboratory values are within therapeutic range of intended use of anticoagulants).
- Haemoglobin <9 g/dl (in absence of blood transfusion within 7 days of value obtained), absolute neutrophil count <1500/µl (1.5 x 109/l), platelet count <100 000/µl (100 x 109/l).
- Any other major illness, any history of a medical condition or a concomitant medical condition that, in the investigator’s judgment, will substantially increase the risk associated with, or compromise the participant’s participation in this trial.
- Participant has known sensitivity to any of the products to be administered during dosing
- Any contraindication to a treatment with the applicable combination partners as mentioned in the prescribing label. Potential contraindications include but are not limited to: active or severe auto-immune disease, history of colitis, hepatitis, pneumonitis; interstitial lung disease or severe pulmonary fibrosis.
- History of treatment with other TEAD inhibitors.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Recruiting | 20 May 2026 | 17 |
 Finland | Not Yet Recruiting | 20 May 2026 | 13 |
 France | Recruiting | 20 May 2026 | 30 |
 Spain | Recruiting | 20 May 2026 | 25 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
NIVOLUMAB | Test | — | INTRAVENOUS ADMINISTRATION | — | — | SUB122750 |
IPILIMUMAB | Test | — | INTRAVENOUS ADMINISTRATION | — | — | SUB29397 |
SOTORASIB | Test | — | ORAL USE | — | — | SUB197397 |
ODM-212 40 mg coated tablet | Test | COATED TABLET | ORAL USE | — | — | PRD11751817 |
PACLITAXEL ALBUMIN-BOUND | Test | — | INTRAVENOUS ADMINISTRATION | — | — | SUB127678 |
ODM-212 5 mg coated tablet | Test | COATED TABLET | ORAL USE | — | — | PRD11751816 |
GEMCITABINE | Test | — | INTRAVENOUS ADMINISTRATION | — | — | SUB07892MIG |