APG-115 in Salivary Gland Cancer Trial

This is a phase I/II trial to evaluate the efficacy of APG-115 +/- Carboplatin for the treatment p53 wild-type malignant salivary gland cancer.

Part 1 consisted of 2 arms, arm A (APG-115 monotherapy) and arm B (APG-115 + Carboplatin) and was terminated early.

Part 2 is a single arm study (APG-115 monotherapy).

The current single arm study design was originally part of a study with a parallel arm given combination APG-115 + Carboplatin. In the initial phase of that previous iteration, the combination arm was closed early for issues related to tolerability of the combination therapy. This study will continue as a single arm, monotherapy alone, Phase I/II study as approved by the UM Institutional Review Board as of June 2021.

Eligibility Criteria:
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

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