IDE892 alone and with IDE397 for MTAP-deleted advanced solid tumors
A Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of IDE892 as Monotherapy and Combination Therapy in Participants With MTAP-Deleted Advanced Solid Tumors
This trial tests IDE892 by itself and combined with IDE397 in adults whose advanced solid tumors have MTAP deletion and have progressed after standard treatments.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 260 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | IDEAYA Biosciences Industry-sponsored |
| Drugs / interventions | chemotherapy, immunotherapy, radiation |
| Locations | 10 sites (Orlando, Florida and 9 other locations) |
| Trial ID | NCT07277413 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1, multicenter, dose-escalation and dose-expansion study of IDE892 as monotherapy and in combination with IDE397 in adults with MTAP-deleted advanced solid tumors. Participants must have central confirmation of MTAP loss from tumor tissue and will provide blood and tissue samples for biomarker and pharmacokinetic testing. The primary focus is on safety, tolerability, and defining appropriate dose(s), with secondary assessments of pharmacokinetics and preliminary anti-tumor activity. The combination with IDE397 (a MAT2A inhibitor) is intended to exploit metabolic vulnerabilities caused by MTAP loss while seeking an acceptable therapeutic index.
Who should consider this trial
Good fit: Adults (≥18) with histologically confirmed, locally advanced or metastatic solid tumors that are MTAP-deleted, who have progressed after standard therapies and can provide required tumor tissue and blood samples, are the intended candidates.
Not a fit: Patients without MTAP deletion, those who have effective standard treatment options available, or those with medical conditions that make them ineligible for the protocol are unlikely to benefit from this study.
Why it matters
Potential benefit: If successful, the agents could offer a new targeted treatment option for patients with MTAP-deleted tumors who have limited standard therapies available.
How similar studies have performed: Preclinical studies support targeting MAT2A and exploiting MTAP loss, but clinical evidence for this specific combination is limited and the combination remains largely untested in humans.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Are ≥ 18 years of age at the time of signing the ICF. * Have a histologically confirmed diagnosis of a locally advanced recurrent or metastatic solid tumor type of interest with MTAP deletion (for dose escalation: mesothelioma \[pleural or peritoneal\], gastroesophageal cancers \[squamous and adenocarcinoma of esophagus, gastric adenocarcinoma, gastroesophageal junction cancers\], NSCLC \[adenocarcinoma, squamous cell carcinoma, and adeno-squamous\] and UC \[including mixed urothelial-squamous histology\]; for dose expansion: NSCLC that has progressed on at least one prior line of treatment and for which additional effective standard therapy is not available or for which the participant is not a candidate due to intolerance). * Are willing and able to provide blood/tumor tissue samples for biomarker testing. An archival tumor tissue specimen must be provided for central confirmation of MTAP loss. * Must be willing and able to provide the blood/serum/plasma samples * Have evidence of homozygous loss of MTAP or MTAP deletion (pre-screening available after signing pre-screening ICF) * Have at least 1 measurable lesion according to RECIST version 1.1 * Have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1 * Have life expectancy \> 3 months * Have adequate bone marrow and organ function * Able to retain administered study drug/IMP. * Male and female: willing to use contraception Exclusion Criteria: * Known symptomatic brain metastases requiring supraphysiologic doses of systemic corticosteroids * Have a known primary central nervous system (CNS) malignancy * Have had other malignancies within 2 years prior to the first dose, with some exceptions * Impaired cardiac function or clinically significant cardiac diseases * Have presence of uncontrolled pleural, peritoneal, or pericardial effusion within 2 weeks before the first study dose, requiring recurrent drainage procedures or an indwelling drainage catheter * Have a history of severe infections within 4 weeks prior to the start of study treatment * Hypertension (e.g., \> 150/100 mmHg) that cannot be controlled by medications despite optimal medical therapy * Other acute or chronic medical or psychiatric condition * Have a history of immunodeficiency, with a positive human immunodeficiency virus(HIV) test at screening * Known or suspected viral hepatitis * Had an adverse reaction to a previous antitumor treatment that has not recovered to CTCAE Grade ≤ 1 * Have received chemotherapy within 3 weeks of the first dose of IMP; immunotherapy or biologic targeted antitumor treatments within 2 weeks before the first dose of IMP; small molecule inhibitors within 2 weeks before the first dose of IMP, or other investigational products within 4 weeks * Current radiation-related toxicity or radiation therapy within 2 weeks before the first dose of IMP * Administration of any of the following within 2 weeks before the first dose of IDE892 as a monotherapy: Strong inhibitors or inducers of cytochrome P450, Strong inhibitors of P-glycoprotein, Narrow therapeutic index and sensitive substrates of multidrug and toxin extrusion (MATE)1 and MATE2-K, Narrow therapeutic index and sensitive substrates of P-gp and breast cancer resistance protein * Administration of any of the following within 2 weeks before the first dose of IDE892: Strong inhibitors or inducers of CYP3A4/5, Strong inhibitors of P-gp and/or BCRP, Narrow therapeutic index and sensitive substrates of MATE1 and MATE2-K, Narrow therapeutic index and sensitive substrates of P-gp and BCRP * Use of proton pump inhibitors (PPIs) within 7 days prior to the first dose of IMP or planned use during the study * Use of drugs with known risk for QT prolongation within 2 weeks prior to the first dose of IDE892 * Previous treatment with a MAT2A inhibitor and/or Protein arginine N-methyltransferase (PRMT) inhibitor * Major surgery within 4 weeks before study entry * Prior irradiation to \> 25% of the bone marrow * Known or suspected hypersensitivity to IDE892 Disease-Specific Eligibility Criteria NSCLC * Must have histologically confirmed diagnosis of advanced or metastatic NSCLC that has progressed after prior treatment with platinum chemotherapy and a PD-1/PD-L1 inhibitor (unless contraindicated or participant developed intolerance) in the metastatic setting * Treatment with no more than 3 prior lines, including no more than 2 prior lines of chemotherapy. * If considered standard of care and available, participants whose cancers have proven targetable oncogene alterations must have had disease progression on (unless contraindicated or participant developed intolerance) at least 1 prior line containing appropriate targeted therapy. Urothelial Cancer (Bladder and Upper Urinary Tract), Mesothelioma (Pleural or Peritoneal) and Gastroesophageal Cancers * Must have histologically confirmed diagnosis of advanced or metastatic UC, mesothelioma, or gastroesophageal cancer * Must have progressed following at least 1 prior line of therapy * Treatment with no more than 3 prior lines, including no more than 2 prior lines of chemotherapy
Where this trial is running
Orlando, Florida and 9 other locations
- Sarah Cannon Research Institute at Florida Cancer Specialists — Orlando, Florida, United States (Recruiting)
- Nebraska Cancer Specialists — Omaha, Nebraska, United States (Recruiting)
- Columbia University Irving Medical Center — New York, New York, United States (Recruiting)
- Sidney Kimmel Comprehensive Cancer Center Thomas Jefferson University — Philadelphia, Pennsylvania, United States (Recruiting)
- Sarah Cannon Research Institute — Nashville, Tennessee, United States (Recruiting)
- START Dallas Fort Worth — Fort Worth, Texas, United States (Recruiting)
- MD Anderson — Houston, Texas, United States (Recruiting)
- NEXT Oncology Houston — Houston, Texas, United States (Recruiting)
- NEXT Oncology Dallas — Irving, Texas, United States (Recruiting)
- NEXT Oncology Virginia — Fairfax, Virginia, United States (Recruiting)
Study contacts
- Study coordinator: IDEAYA Clinical Trials
- Email: IDEAYAClinicalTrials@ideayabio.com
- Phone: +1 855 433 2246
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.