A 2-part Phase 1/2 Open-label Trial Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ODM-212 in Combination With Anti-cancer Therapy in Participants With Advanced Solid Tumours

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Trial Details

Sponsor: Orion Corporation, Orion Pharma (industry)

Phase: 1/2

Start date: March 27, 2026

Planned enrollment: 229

Trial ID: NCT07563738
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More trial details at ClinicalTrials.gov More info

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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

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Sites (2)

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NEXT Oncology

Irving, Texas, 75039, United States

No email / No phone

Status: Recruiting

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

[email protected] / No phone

Status: Recruiting

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