Clinical Trial 24273

• Overview

  Study Title:

  A Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of IDE892 as Monotherapy and Combination Therapy in Participants With MTAP-Deleted Advanced Solid Tumors

  Summary:

  This is a multicenter clinical study to evaluate the safety, efficacy, and Pharmacokinetics (PK) of IDE892 as monotherapy and in combination with other agents including IDE397 in participants with methylthioadenosine phosphorylase (MTAP)-deleted advanced solid tumors within indications of interest.

  Objective:

  Dose Escalation Primary: -To assess the safety and tolerability of increasing dose levels of IDE892 in participants with locally advanced recurrent or metastatic tumors with MTAP deletion including mesothelioma, gastroesophageal cancer, pancreatic and biliary tract tumors, non-small cell lung cancer (NSCLC) (adenocarcinoma, squamous cell carcinoma and adeno-squamous carcinoma) and urothelial cancers (UC) (bladder and upper urinary tract; including mixed urothelial-squamous histology) to determine the maximum tolerated dose (MTD) and/or the recommended dose/s for expansion (RDE) -To assess the safety and tolerability at increasing dose levels of IDE892 in combination with IDE397 in locally advanced recurrent or metastatic tumors with MTAP deletion including mesothelioma, gastroesophageal cancers, pancreatic and biliary tract tumors, NSCLC, and UC to determine the MTD and/or the RDE for the combination Dose Expansion Primary: -To further assess the safety and tolerability of 2 or more dose levels of IDE892 at or below the MTD to determine the recommended Phase 2 dose (RP2D) in advanced or metastatic NSCLC with MTAP deletion -To evaluate the antitumor activity of IDE892 in participants with advanced or metastatic NSCLC with MTAP deletion -To further assess the safety and tolerability of 2 or more dose levels of IDE892 in combination with IDE397 at or below the MTD to determine the recommended Phase 2 dose (RP2D) in advanced or metastatic NSCLC with MTAP deletion -To evaluate the antitumor activity of IDE892 in combination with IDE397 in advanced or metastatic NSCLC with MTAP deletion Dose Escalation Secondary: -To evaluate preliminary antitumor activity of IDE892 in participants with advanced or metastatic tumors with MTAP deletion including mesothelioma, gastroesophageal cancers, pancreatic and biliary tract tumors, NSCLC, and UC as monotherapy or in combination with IDE397 Dose Escalation/Expansion Secondary: -To evaluate antitumor activity of IDE892 as monotherapy or in combination with IDE397 in tumor types of interest by other measures -To evaluate the pharmacokinetics (PK) of IDE892 as monotherapy or in combination with IDE397 -To evaluate the PK of IDE397 when combined with IDE892

• Treatments

  Therapies:

  MAT2A Inhibitor; PRMT5 Inhibitior

  Medications:

  IDE397 (); IDE892 ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • 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.

• Exclusion Criteria

  Key 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 with a positive test at screening.
  • 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.
  • Use of drugs with known risk for QT prolongation within 2 weeks prior to the first dose of IDE892.
  • 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.
  • Known or suspected hypersensitivity to IDE892.

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