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
Recruiting
Phase 1/Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| APG-115 | APG-115 + Carboplatin | |
| Carboplatin | APG-115 + Carboplatin |
This is an open label multi-institution phase I/II study with an initial randomized component
then followed by a planned single-arm phase. Arms will be monitored using the time-to-event
continual reassessment method (TITE-CRM). In the initial randomized phase, patients will be
randomized to one of two arms: Arm A (APG-115 alone) or Arm B (APG-115 + Carboplatin) at a
ratio of 1:2. After 14 patients have been accrued in Arm A and 28 patients have been accrued
to Arm B, responses will be tabulated. The outcomes of the arms will be considered, and a
single arm will be selected for further study in part 2 of the study. Response rate (defined
as CR or PR after cycle 2) will be the foremost consideration for deciding on the most
promising arm; in addition, a comprehensive evaluation of the available data including
toxicity and pharmacokinetic (PK) data will also be considered. After an arm has been chosen
to advance an additional 20 patients will be accrued.
| Name | Type | Description | Interventions |
|---|---|---|---|
| APG-115 monotherapy | Experimental | APG-115 at 150mg is taken orally every other day within one hour after food. Cycle length 21 days |
|
| APG-115 + Carboplatin | Experimental | 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. |
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Primary Toxicity Endpoint: dose-limiting toxicity (DLT) |
| Time Frame: | 42 days |
| Safety Issue: | |
| Description: | 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 |
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Ascentage Pharma Group Inc. |
May 28, 2021
