Sequence of androgen receptor-targeted vaccination with androgen deprivation therapy affects anti-prostate tumor efficacy.

Rationale: Androgen deprivation therapy (ADT) is the primary treatment for recurrent and metastatic prostate cancer. In addition to direct antitumor effects, ADT has immunomodulatory effects such as promoting T-cell infiltration and enhancing antigen processing/presentation. Previous studies in our laboratory have demonstrated that ADT also leads to increased expression of the androgen receptor (AR) and increased recognition of prostate tumor cells by AR-specific CD8+T cells.

A first in man study to evaluate the safety, pharmacokinetics and pharmacodynamics of RP7214, a dihydroorotate dehydrogenase inhibitor in healthy subjects.

Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that is essential for pyrimidine de novo synthesis. Rapidly growing cancer cells and replicating viruses are dependent on host cell nucleotides, the precursors of which are provided by DHODH. Hence, DHODH becomes an ideal target for pharmacological intervention.

A first-in-human study to evaluate the safety, tolerability and pharmacokinetics of RP3128, an oral calcium release-activated calcium (CRAC) channel modulator in healthy volunteers.

What Is Known And Objective: RP3128, a novel, orally available modulator of calcium released activated calcium (CRAC) channel, is being developed for the potential treatment of autoimmune and inflammatory diseases. RP3128 showed nano-molar potency and activity in a range of in vitro and in vivo models of inflammation. We report a first-in-human study investigating the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RP3128 in healthy subjects.

Phase I/Ib Study of Tenalisib (RP6530), a Dual PI3K δ/γ Inhibitor in Patients with Relapsed/Refractory T-Cell Lymphoma.

Tenalisib (RP6530), a dual phosphoinositide 3-kinase δ/γ inhibitor was evaluated in a phase I/Ib study for maximum tolerated dose (MTD), pharmacokinetics, and efficacy in patients with relapsed/refractory peripheral and cutaneous T-Cell Lymphoma (TCL). Histologically confirmed (TCL) patients, with ≥1 prior therapy received Tenalisib orally in a 28-day cycle in doses of 200 to 800 mg twice daily (800 mg in fasting and fed state) in escalation phase ( = 19) and 800 mg twice daily (fasting) in expansion phase ( = 39). The most frequently reported treatment emergent adverse events (TEAE) and related TEAE were fatigue (45%) and transaminase elevations (33%), respectively.

A First-in-human Study of Tenalisib (RP6530), a Dual PI3K δ/γ Inhibitor, in Patients With Relapsed/Refractory Hematologic Malignancies: Results From the European Study.

Background: Tenalisib (RP6530) is a novel, highly specific, dual phosphoinositide-3 kinases (PI3K) δ/γ inhibitor with nano-molar potency.

Material And Methods: This was a phase I, open-label, 3 + 3 dose escalation, maximum tolerated dose determination study to evaluate the safety, pharmacokinetics, and efficacy of tenalisib in patients with relapsed/refractory hematologic malignancies. Tenalisib was administered orally twice/thrice daily in 28-day cycles with starting dose of 25 mg twice daily.