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Ref Type Journal Article
PMID (31761713)
Authors Carlo-Stella C, Delarue R, Scarfo L, Barde PJ, Nair A, Locatelli SL, Morello L, Magagnoli M, Vakkalanka S, Viswanadha S, Ferreri AJM
Title 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.
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Abstract Text Tenalisib (RP6530) is a novel, highly specific, dual phosphoinositide-3 kinases (PI3K) δ/γ inhibitor with nano-molar potency.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.Thirty-five patients were enrolled across 11 dose levels. No dose limiting toxicity was reported at any of the dose levels. The most common treatment-emergent adverse events irrespective of causality were asthenia and cough in 15 (43%) patients and pyrexia in 13 (37%) patients. The most frequently reported related treatment-emergent adverse events were diarrhea, nausea, and vomiting. Related grade 3/4 adverse events were limited to events of hypertriglyceridemia, neutropenia, and diarrhea. Pharmacokinetics showed rapid absorption. Based on maximum plasma concentration and area under the plasma-concentration time curve, dose proportionality was observed up to 400 mg dose. Of 31 patients included in the efficacy analysis, complete response was seen in 2 (7%) patients and partial response in 4 (13%) patients, with an overall response rate of 19% and a disease-control rate of 61%. The median duration of response was 5.7 months. Responders demonstrated a marked downregulation of phospho-AKT on C1D8.Tenalisib demonstrated acceptable safety up to 1200 mg twice a day with no dose-limiting toxicities. Consistent clinical response was seen at doses 200 mg BID and above. Pharmacodynamics correlated well with clinical outcome. Further phase I/II studies are being undertaken to evaluate efficacy across different histologies.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Tenalisib Tenalisib 0 3
Drug Name Trade Name Synonyms Drug Classes Drug Description
Tenalisib RP6530|RP-6530|RP 6530 PIK3CD inhibitor 27 PIK3CG inhibitor 10 Tenalisib (RP6530) is an inhibitor of PIK3CG and PIK3CD, which blocks PI3K/AKT signaling to prevent cell proliferation and also may modulate the tumor microenvironment and induce macrophage phenotype conversion from M2 to M1 (PMID: 30352904, PMID: 31761713, PMID: 32824175).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References