Sponsor: Orion Corporation, Orion Pharma (industry)
Phase: 1/2
Start date: March 27, 2026
Planned enrollment: 229
ODM-212 is an investigational oral small-molecule pan-TEAD inhibitor developed by Orion Pharma for cancers associated with Hippo pathway dysregulation. It is being studied in the Phase 1/2 TEADES trial in selected advanced solid tumors, including malignant pleural mesothelioma, epithelioid hemangioendothelioma, and other tumors after progression on standard therapies. The Phase 2 portion began after the first patient was treated in December 2025 and is planned to enroll approximately 300 patients. (orionpharma.com)
ODM-212 received FDA orphan drug designation for mesothelioma in April 2026. Orphan designation is not approval and does not by itself shorten development or regulatory review. (orionpharma.com)
ODM-212 targets TEAD transcription factors in the Hippo signaling pathway. Hippo pathway dysregulation, particularly YAP/TAZ activation, can promote tumor growth and resistance to cancer therapies. ODM-212 is described as blocking TEAD transcription factors, disrupting YAP–TEAD protein–protein interactions, and inhibiting TEAD auto-palmitoylation, a modification required for TEAD activity. (orionpharma.com)
The ongoing TEADES study is a multi-center, open-label Phase 1/2 trial of ODM-212 tablets in adults with selected advanced solid tumors. A Memorial Sloan Kettering Cancer Center trial page describes the study goal as finding the best dose of ODM-212 in people whose solid tumors have spread and cannot be cured with standard therapies; examples include mesothelioma, epithelioid hemangioendothelioma, schwannoma, meningioma, renal cell cancer, cholangiocarcinoma, head and neck cancer, lung cancer, colorectal cancer, liver cancer, and prostate cancer. (mskcc.org)
The Phase 2 study’s primary endpoints are safety and tolerability; secondary endpoints include overall response rate, progression-free survival, and overall survival. (orionpharma.com)
No peer-reviewed clinical efficacy results or detailed response rates for ODM-212 were found in the searched sources. Orion has stated that Phase 1 results showed “clinical activity” as monotherapy and that preliminary EHE results were presented at the CTOS annual meeting in November 2025, but the searched public sources did not provide response rates or detailed outcome data. Orion indicated that Phase 1 TEADES results are planned for presentation at a scientific conference in 2026. (orionpharma.com)
No peer-reviewed safety dataset was found in the searched sources. Orion has described the Phase 1 safety profile as “manageable” across different doses and schedules, but detailed adverse-event rates were not available in the retrieved public sources. Safety and tolerability remain the primary endpoints of the Phase 2 TEADES study. (orionpharma.com)
Last updated: May 2026
Goal: To determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ODM-212 when combined with established anticancer regimens in selected advanced solid tumors. The study includes dose escalation to identify tolerable dosing and dose expansion/optimization to further characterize safety and antitumor activity in defined disease cohorts.
Patients: Adults aged 18 years or older with ECOG performance status 0–1, life expectancy greater than 12 weeks, and advanced or metastatic unresectable solid tumors eligible for one of the study combination regimens. Disease-specific cohorts include unresectable or metastatic mesothelioma eligible for ipilimumab/nivolumab, metastatic pancreatic ductal adenocarcinoma eligible for gemcitabine plus nab-paclitaxel, and locally advanced or metastatic KRAS G12C-mutated NSCLC eligible for sotorasib, including both KRAS G12C inhibitor–naïve and KRAS G12C inhibitor–pretreated patients in Part 2. Part 2 requires measurable disease by RECIST 1.1, or modified RECIST for mesothelioma, available recent tumor tissue, and willingness to undergo paired fresh tumor biopsies. Key exclusions include active recent malignancy, uncontrolled or unresolved prior treatment toxicity, untreated or symptomatic brain metastases, significant infection, HIV/HBV/HCV positivity as specified, clinically important cardiac disease or QT prolongation, recent major surgery or radiotherapy, immunosuppressive steroid doses, and conditions impairing oral drug absorption.
Design: This is an open-label, multicenter, nonrandomized, multi-cohort phase 1/2 study with two parts. Part 1 is a dose-escalation component evaluating ODM-212 with different backbone anticancer therapies. Part 2 is a dose-expansion/optimization component in disease-specific cohorts to further define safety, pharmacodynamic effects, and preliminary efficacy at selected doses. All participants receive ODM-212 in combination with the assigned standard anticancer regimen; there is no placebo or randomized comparator arm.
Treatments: ODM-212 is being studied in combination with ipilimumab plus nivolumab for mesothelioma, with gemcitabine plus nab-paclitaxel for metastatic pancreatic adenocarcinoma, and with sotorasib for KRAS G12C-mutated NSCLC. ODM-212 is an investigational oral pan-TEAD inhibitor targeting TEAD transcription factors in the Hippo pathway, a pathway implicated in YAP/TAZ-driven tumor growth, survival, and treatment resistance. Its proposed mechanisms include disruption of YAP–TEAD signaling and inhibition of TEAD auto-palmitoylation, thereby reducing TEAD transcriptional activity. No peer-reviewed clinical efficacy or detailed safety results are available yet; sponsor communications have described early phase 1 activity and a manageable safety profile, but response rates and adverse-event frequencies have not been publicly established. Ipilimumab and nivolumab are immune checkpoint inhibitors targeting CTLA-4 and PD-1, respectively, and are an established systemic option in unresectable malignant pleural mesothelioma. Gemcitabine plus nab-paclitaxel is a standard cytotoxic chemotherapy regimen for metastatic pancreatic adenocarcinoma. Sotorasib is an oral KRAS G12C inhibitor used in KRAS G12C-mutated NSCLC, and this trial includes both KRAS G12C inhibitor–naïve and previously treated cohorts.
Outcomes: The primary outcome is the incidence and severity of dose-limiting toxicities, adverse events, and clinical laboratory abnormalities, assessed through study completion, approximately 2 years on average. The trial also evaluates pharmacokinetics, pharmacodynamics, and preliminary antitumor efficacy, including response-based assessments in the expansion cohorts where measurable disease is required.
Burden on patient: The expected patient burden is high. This is an early-phase combination trial involving an investigational oral agent plus standard systemic therapy, with likely frequent visits during dose escalation and early treatment cycles, intensive safety monitoring, laboratory testing, ECG/cardiac assessments, and pharmacokinetic blood sampling. Part 2 also requires recent tumor tissue and paired fresh biopsies at screening and on treatment, which adds procedural burden and potential discomfort or risk. Travel burden may be substantial because treatment and monitoring occur at specialized trial sites, and participants must also maintain daily adherence records for oral ODM-212.
Last updated: May 2026
Inclusion Criteria:
* 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.
* Part 1: Participants with histologically or cytologically confirmed advanced or metastatic, unresectable solid tumors and who are able and willing to receive one of the anti-cancer therapies studied in this trial according to the investigator.
* Arm A: Participants with histologically or cytologically confirmed diagnosis of advanced (unresectable or metastatic) mesothelioma who are eligible to receive treatment with ipilimumab/nivolumab; participants must not have undergone surgical therapy for mesothelioma.
* Arm B: Participants with histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas who are eligible to receive treatment with nab-paclitaxel and gemcitabine.
* Arm C: Participants with histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC and a KRAS G12C-mutation, confirmed using a validated test, who have received the available 1st line treatment and who are eligible for a treatment with sotorasib and have not received a KRAS G12C inhibitor as prior treatment.
Part 2:
* Ipilimumab/nivolumab cohort: Participants with histologically or cytologically confirmed diagnosis of advanced (unresectable or metastatic) mesothelioma who are eligible to receive a treatment with ipilimumab/nivolumab. Prior treatment with ipilimumab, nivolumab and/or other PD-1/PD-L1/CTLA-4 inhibitors for advanced or metastatic disease is not allowed.
* Nab-paclitaxel/gemcitabine cohort: Participants with histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas who are eligible to receive a treatment with nab-paclitaxel and gemcitabine. Previous treatments with nab-paclitaxel and/or gemcitabine for metastatic disease are not allowed.
* Sotorasib cohort, treatment naïve: Participants with histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC and a KRAS G12C-mutation, confirmed using a validated test, who are eligible for a treatment with sotorasib and have not received a KRAS G12C inhibitor as prior treatment.
* Sotorasib cohort, pretreated: Participants with histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC and a KRAS G12C mutation, confirmed using a validated test, who have documented progression on a prior KRAS G12C inhibitor (approved or investigational).
* Part 2 only: Participants must have measurable disease by response evaluation criteria in solid tumours (RECIST) v. 1.1 (modified RECIST for MPM).
* 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.
* Amenable for paired fresh tumour biopsy at screening period and on-treatment.
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 has completed curative therapy.
* Prior chemotherapy, immunotherapy (immune checkpoint inhibitor, tumour vaccine, cytokine or growth factor given to control the cancer) or other anti-cancer therapy within less than 2 weeks before trial treatment administration.
* Any persistent unresolved toxicity from previous anti-cancer therapies of 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, 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 IMP 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, 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.
Irving, Texas, 75039, United States
No email / No phone
Status: Recruiting
Fairfax, Virginia, 22031, United States
[email protected] / No phone
Status: Recruiting