Single Agent ONC201 in Recurrent or Metastatic Endometrial Cancer
Status:
Suspended
Trial end date:
2023-06-01
Target enrollment:
Participant gender:
Summary
ONC201 is a small molecule which selectively targets the G protein-coupled receptor DRD2.
Downstream of target engagement, ONC201 activates the integrated stress response (ISR) in
tumor cell leading to inactivation of Akt and extracellular signal-regulated kinase (ERK)
signaling as well as induction of the TRAIL pathway. ONC201 also inhibits dopamine receptor 2
(DRD2), resulting in anti-tumor responses in preclinical models. Single agent ONC201 has been
examined in open-label Phase I studies in patients with advanced, treatment refractory solid
malignancies. Due to its differential anti-proliferative and pro-apoptotic response in tumor
cells, treatment was overall well tolerated, and the recommended phase II dose of ONC201 was
set at 625mg every three weeks. An additional dose-escalation phase I study (NCT02609230) is
further evaluating weekly versus three week dosing in patients with advanced solid tumors and
multiple myeloma. Preliminary data from these phase I studies suggests a possible clinical
benefit in patients with advanced, chemo-refractory endometrial cancers, with at least one
mixed response noted in a patient with clear cell histology.
Hypothesis: Single agent ONC201 will demonstrate clinical benefit in women with recurrent or
metastatic endometrial cancers, especially in those women with alterations in the
Phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of Rapamycin (mTOR) pathway.