A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies.

Purpose: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.

Methods: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles.

Estrogens and breast cancer.

Estrogens have been associated with an increase in breast cancer risk. Yet emerging clinical and experimental evidence points to progestogens [endogenous progesterone or synthetic progesterone (progestin)] as the primary hormonal driver underlying seemingly estrogen-associated breast cancer risk. Estrogens may contribute to breast cancer risk indirectly by induction of the progesterone receptor and thus amplifying progesterone signaling.

Updated Survival Follow-Up for Phase Ib Trial of the Histone Deacetylase Inhibitor Abexinostat With Pazopanib in Patients With Solid Tumor Malignancies.

Purpose: Histone deacetylase (HDAC) inhibition downregulates hypoxia-inducible factor-1α and modulates multiple metabolomic pathways relevant in cancer. Here we report a potential novel biomarker to predict exceptional responders (>3 years) in patients receiving HDAC and vascular endothelial growth factor (VEGF) inhibition.

Patients And Methods: Patients with solid tumor malignancies were enrolled in this phase Ib trial of abexinostat (4/7 ×21 days) and pazopanib (28/28 days), with a dose expansion in renal cell carcinoma (RCC).

ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors.

Purpose: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial.

Patients And Methods: The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel.

A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170).

Unlabelled: We sought to evaluate the efficacy of WEE1 inhibitor adavosertib in patients with solid tumor malignancies (cohort A) and clear cell renal cell carcinoma (ccRCC; cohort B). NCT03284385 was a parallel cohort, Simon two-stage, phase II study of adavosertib (300 mg QDAY by mouth on days 1-5 and 8-12 of each 21-day cycle) in patients with solid tumor malignancies harboring a pathogenic SETD2 mutation. The primary endpoint was the objective response rate.