• Primary Toxicity Endpoint: dose-limiting toxicity (DLT) [ Time Frame: 42 days ]
  DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 6 weeks (2 cycles) of study treatment. These will be assessed via CTCAE version 5.0
• Maximally tolerated dose (MTD) [ Time Frame: 42 days ]
  MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment.
• Overall response rate [ Time Frame: up to 12 months ]
  Overall response rate will be defined as the proportion of patients achieving either complete response (CR) or partial response (PR). Response will be assessed via RECIST v1.1.

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 consists of 2 arms, arm A is APG-115 monotherapy and arm B is APG-115 + Carboplatin

Part 2 is single arm based on the outcome of part 1

• Malignant Salivary Gland Cancer
• Salivary Gland Cancer

• Drug: APG-115
  APG-115 at 150mg is taken orally every other day within one hour after food. Cycle length 21 days.
• Drug: Carboplatin
  Carboplatin is given IV at AUC=4.5. Cycle length 21 days.

• Experimental: APG-115 monotherapy
  APG-115 at 150mg is taken orally every other day within one hour after food. Cycle length 21 days
  Intervention: Drug: APG-115
• Experimental: APG-115 + Carboplatin
  APG-115 at 150mg is taken orally every other day within one hour after food. Carboplatin is given IV at AUC=4.5. Cycle length 21 days.
  Interventions:

  • Drug: APG-115
  • Drug: Carboplatin

Inclusion Criteria:

• Histologically documented high grade malignant salivary gland cancers 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 breast-feeding