A Study of IDE892 as Monotherapy and Combination in 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.

Eligibility

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

Conditions13

Locations3 sites

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