Novel PKC Inhibitor Trial to Expand Its Cohort of Patients With Solid Tumors

The phase 2 basket arm trial of IDE196 in patients with solid tumors harboring GNAQ or GNA11 hotspot mutations has met its clinical protocol criteria for cohort expansion. The trial will begin enrolling the remaining patients in the first half of 2021 due to the anticipated impact of the coronavirus disease 2019.

"I am pleased IDE196 has met the criteria for Stage 2 expansion in skin melanoma, as these patients with GNAQ/11 mutations may not have actionable BRAF driver mutations and may also have a low tumor mutational burden, and thus be less responsive to existing treatment options," said Marlana Orloff, MD, assistant professor, Thomas Jefferson University Hospital, and principal investigator of the clinical trial, in a statement.

Thus far, 4 evaluable patients have been enrolled in addition to 1 patient with GNAQ/11-mutant melanoma who is not evaluable for response. These patients will be treated in the initial 1 stage cohort. To continue on to the phase 2 portion of the study, 9 patients must achieve a response per Response Evaluation Criteria in Solid Tumors version 1.1(RECIST v 1.1). In phase 2, 15 additional patients may enroll, bringing the total number of trial participants to 24.

Prior to meeting protocol for cohort expansion, the study had already made some progress. The first patient with leiomyosarcoma was dosed with IDE196, which broaden the tumor types treated in the study. Additionally, 1 confirmed partial response per RECIST v1.1 was observed in a patient with melanoma. Finally, the study investigators completed their 13-week preclinical toxicity reports of the agent.

The primary goals of the multi-center, open-label basket study in phase 1 are to measure the pharmacokinetics of IDE196, the dose-limiting toxicities of IDE196 , and to determine the maximum tolerated dose and recommended phase 2 dose of the agent. The primary end point for phase 2 of the study is overall response rate. The secondary end points include duration of response, disease control, and the number of patients with adverse events. The study is also exploring overall survival and progression-free survival.

In terms of eligibility, patients with metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors who harbor GNAQ/11 mutations or PRKC fusions are eligible. These patients are required to be at least 18 years of age with measurable disease, an ECOG performance status of 0 to 1, and adequate organ function at the time of screening. The study excludes individuals who have been diagnosed with another malignancy and those who have known microsatellite instability-high tumors, unresolved AEs from prior anti-cancer treatment, untreated or symptomatic central nervous system metastases, a diagnosis of human immunodeficiency virus, and those who have had recent surgery or radiotherapy.

The overall target enrollment for the study is 166 patients, who will receive IDE196 monotherapy twice daily for each 28-day cycle.

"IDE196 expansion in skin melanoma enables IDEAYA to build a larger data set and to explore potential combinations in this tumor type, and further validates our GNAQ/11 tissue-agnostic approach," said Mick O'Quigley, vice president, head of Development Operations at IDEAYA Biosciences, in a statement.

_Reference:

_{IDEAYA announces IDE196 program update and clinical protocol criteria met for cohort expansion in skin melanoma for phase 2 gnaq/11 basket trial. News release. IDEAYA BioSciences. July 16, 2020. Accessed July 16, 2020. https://bit.ly/3ja9Vkd}