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Carboplatin

APG-115 will be administered in an open label fashion until progression, intolerance, or patient preference.

APG-115 and Carboplatin will be administered in an open label fashion until progression, intolerance, or patient preference. \[Phase 1 was terminated early and this arm was discontinued. An MTD was not established during Phase 1.\]

APG-115 at 150mg (or lower, if dose is reduced) is taken orally every other day through day 13 of each cycle. Cycle length 21 days.

APG-115

Carboplatin is given IV at AUC=4.5 on day 1 of each cycle. Cycle length 21 days.

Paul L Swiecicki, MD

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.

Part 1 -- Parallel assignment \[terminated early\]:

* Arm A: APG-115 Monotherapy
* Arm B: APG-115 + Carboplatin

Part 2 -- Single arm (Arm A only): APG-115 Monotherapy

APG-115 in Salivary Gland Cancer Trial

A Multicenter Phase I/II Trial of a Novel MDM2 Inhibitor (APG-115) in p53 Wild-type Salivary Gland Carcinoma

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

MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment.

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.

Overall response rate will be defined as the proportion of patients achieving either complete response (CR) or partial response (PR), assessed via RECIST v1.1 and reported separately for those with histologically confirmed adenoid cystic carcinoma (ACC) versus other malignant salivary gland tumors (non-ACC)

The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started.

Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever is earlier.

Overall survival (OS) is defined as the duration of time from start of treatment to time of death or end of study.

Defined as the proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD). Response will be assessed via RECIST v1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
APG-115 in Salivary Gland Cancer Trial	NCT03781986	Malignant Saliv... Salivary Gland ...	APG-115 Carboplatin	18 Years -	University of Michigan Rogel Cancer Center
APG-115 in Salivary Gland Cancer Trial	NCT03781986	Malignant Saliv... Salivary Gland ...	APG-115 Carboplatin	18 Years -	University of Michigan Rogel Cancer Center

Spots Global Cancer Trial Database for malignant salivary gland cancer