A Multicenter Phase I/II Trial of a Novel MDM2 Inhibitor (APG-115) in P53 Wild-Type Salivary Gland Carcinoma
This is a Phase I/II study to determine the efficacy of APG-115 monotherapy for the treatment of p53 wild-type malignant salivary gland cancer.
Primary Objectives: To determine the dose-limiting toxicity (DLT) and maximally tolerated dose (MTD) for APG-115 as with a monotherapy or when given in combination with carboplatin. To assess evidence of anti-tumor activity by assessment of overall response rate in patients with malignant salivary gland cancer for APG-115 as with a monotherapy or when given in combination with carboplatin. Secondary Objectives: To describe the adverse effects associated with APG-115 monotherapy or when given in combination with carboplatin. To assess progression free survival (PFS), Duration of response (DoR), overall survival (OS) and disease control rate (DCR) in patients with p53 wild type malignant salivary gland cancers treated with APG-115 monotherapy or when given in combination with carboplatin. To assess overall response rate (ORR) by tumor histology (ACC vs. non-ACC)
- Inclusion Criteria:
- Histologically documented malignant salivary gland cancers (including secretory glands of the aerodigestive tract) with or without metastases, not amenable to curative treatment; or there is documentation of patient refusal of curative treatment.
- Previous mutational testing with no evidence of a p53 mutation
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
- Presence of measurable disease by CT scan per RECIST v1.1 with ≥ 20% increase in tumor burden in the preceding 12 months
- Life expectancy of ≥12 weeks
- Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
- Patients must be able to take oral medication without breaking/opening, crushing, dissolving, or chewing capsules
- Adequate organ and marrow function obtained ≤ 2 weeks prior to enrollment
- Additional criteria may apply
- Exclusion Criteria:
- Prior treatment with MDM2 inhibitors
- Patients are not eligible if they have received any systemic anti-cancer therapy (including chemotherapy and/or hormone therapy) for salivary gland cancer within 4 weeks of the start of study therapy
- Patients are not eligible if they have received any of the following within 4 weeks of the start of study therapy: live vaccines, antiretroviral drugs
- Progressive disease within 6 months of the last dose of platinum-based chemotherapy
- Patients with active brain metastases are excluded because of unknown penetration into the central nervous system (CNS). A confirmatory scan for asymptomatic patients is not required. Patients with a history of treated CNS metastases are eligible provided they meet all of the following criteria: disease outside the CNS is present, no clinical evidence of progression since completion of CNS-directed therapy, minimum 4 weeks between completion of radiotherapy and enrollment, and recovery from significant (Grade ≥ 3) acute toxicity.
- A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment
- Patients (male and female) having procreative potential who are not willing or not able to use 2 adequate methods of contraception or practicing abstinence during the study and for 90 days following their last dose of treatment
- Women who are pregnant or breast-feeding
- Additional exclusions may apply
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