A phase I dose escalation study of the HIF-2 alpha inhibitor DFF332 in patients with advanced clear cell renal cell carcinoma.

Background: Mutations or silencing of the von Hippel Lindau (VHL) tumor suppressor gene accumulates hypoxia-inducible factors (HIFs). HIF-2α is implicated in the oncogenesis of ~50% of patients with clear cell renal cell carcinoma (ccRCC) but, has been considered "undruggable". DFF332, an orally administered novel allosteric inhibitor of HIF-2α showed dose-dependent antitumor efficacy in preclinical models of ccRCC.

A Phase I Study of LSZ102, an Oral Selective Estrogen Receptor Degrader, with or without Ribociclib or Alpelisib, in Patients with Estrogen Receptor-Positive Breast Cancer.

Purpose: Data are sparse for oral selective estrogen receptor (ER) degraders (SERD) in cancer treatment. The investigational oral SERD LSZ102 was assessed in monotherapy and combination use in a phase I study.

Patients And Methods: A phase I, multicenter, open-label dose-escalation study (NCT02734615) of LSZ102 alone (arm A; = 77) or with ribociclib (arm B; = 78) or alpelisib (arm C; = 43) in heavily pretreated adults with histologically confirmed ER-positive breast cancer and prior disease progression.

Unexpected hepatotoxicity in a phase I study of TAS266, a novel tetravalent agonistic Nanobody® targeting the DR5 receptor.

Purpose: TAS266 is a novel agonistic tetravalent Nanobody(®) targeting the DR5 receptor. In preclinical studies, TAS266 was more potent than a cross-linked DR5 antibody or TRAIL. This first-in-human study was designed to evaluate the safety and tolerability, maximum tolerated dose, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of TAS266.