A Study of IDE892 as Monotherapy and Combination in MTAP-deleted Advanced Solid Tumors

Korábbi kezelés

• Known symptomatic brain metastases requiring supraphysiologic doses of systemic corticosteroids
• Have had other malignancies within 2 years prior to the first dose, with some exceptions
• 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
• Had an adverse reaction to a previous antitumor treatment that has not recovered to CTCAE Grade ≤ 1
• Have received chemotherapy within 4 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
• Previous treatment with a Amethionine adenosyltransferase 2A (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
• 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 in the setting of advanced or metastatic disease.
• 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.
  • Eligibility Criteria for Participants with Urothelial Cancer (Bladder and Upper Urinary Tract), Mesothelioma (Pleural or Peritoneal), Pancreatic Adenocarcinoma or Biliary Tract Carcinomas (Intrahepatic and Extrahepatic Cholangiocarcinoma, and Gallbladder Cancer) (Parts 1 and 3)
• Must have progressed following at least 1 prior line of therapy
• Treatment with no more than 3 prior lines in the setting of advanced or metastatic disease

Más betegség

• Have a known primary central nervous system (CNS) malignancy
• Impaired cardiac function or clinically significant cardiac diseases
• 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 with a positive test at screening
• Known or suspected hypersensitivity to IDE892
  • Disease-Specific Eligibility Criteria Eligibility Criteria for Participants with NSCLC (All Parts)
• Must have histologically confirmed diagnosis of advanced or metastatic UC, mesothelioma, gastroesophageal cancer or pancreatic and biliary tract tumors

Laborértékek

• Use of drugs with known risk for QT prolongation within 2 weeks prior to the first dose of IDE892

• Are ≥ 18 years of age (or the minimum age of consent in accordance with local regulations) 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], pancreatic adenocarcinoma and biliary tract carcinomas (intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer), NSCLC [adenocarcinoma, squamous cell carcinoma, and adeno-squamous] or 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 swallow and retain orally administered study drug/IMP.
• Are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
• Male and female: willing to use contraception