Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : firstname.lastname@example.org
|Authors||Robin Lewis Jones, Teresa Macarulla, John A. Charlson, Brian Andrew Van Tine, Lipika Goyal, Antoine Italiano, Christophe Massard, Mark Rosenthal, Macarena Ines De La Fuente, Patricia Roxburgh, Madappa N. Kundranda, Jean-Yves Blay, Changhoon Yoo, Kate Lipford, Sanjeev Forsyth, Sylvie Mireille Guichard, Yelena Mikhailov, Blythe Thomson, Patrick Francis Kelly, Florence Duffaud|
|Title||A phase Ib/II study of olutasidenib in patients with relapsed/refractory IDH1 mutant solid tumors: Safety and efficacy as single agent.|
|Journal||Journal of Clinical Oncology|
|Date||May 25, 2020|
|Abstract Text||Background: Isocitrate dehydrogenase 1 mutations (mIDH1) are present in a variety of solid tumors resulting in production and accumulation of (R)-2-hydroxyglutarate causing DNA hypermethylation and promoting tumorigenesis. Olutasidenib is an oral, potent and selective inhibitor of mutated IDH1 protein. We report preliminary results from the ongoing, first-in-human, Phase 1, open-label, single-arm study of olutasidenib in non-CNS solid tumors. Methods: Patients with advanced relapsed/refractory (R/R) mIDH1 solid tumors received olutasidenib 150 mg BID, orally. Following a dose confirmation cohort (Phase 1b), patients with intrahepatic cholangiocarcinoma (IHCC), chondrosarcoma (CS), or unspecified mIDH1 solid tumors (Other) were enrolled in a Phase 2 efficacy evaluation (NCT: 03684811). Results: As of 31-Oct-2019, 44 patients with relapsed or refractory mIDH1 solid tumors were treated with olutasidenib. Diagnosis included: IHCC (n = 26), CS (n = 13), and Other (n = 5). The median age was 58 years (range: 29-81) and 43% were male. Median number of prior treatments was 2 (1-10). mIDH1 status was locally determined (IHC, NGS or PCR): R132C (61%), R132G (7%), R132S (7%), R132H (2%), R132L (2%), Others (2%) & unspecified (18%). Fourteen patients discontinued treatment (disease progression [n = 6; 3 IHCC, 2 CS, 1 Other], AE [n = 4; 3 IHCC, 1 CS], PI decision [n = 3; IHCC] & withdraw consent [n = 1; IHCC]). Treatment emergent adverse events (all grades, regardless of attribution) that occurred in > 15% of pts were: nausea (43%), fatigue (25%), decreased appetite (22%), AST increase (18%), ALT increase (16%), and constipation (16%). No protocol-defined DLTs occurred. Best responses by tumor type are shown in the table. Conclusions: Single agent olutasidenib at 150 mg BID demonstrates acceptable safety and tolerability with preliminary clinical activity in patients with R/R mIDH1 solid tumors. Updated safety and clinical activity, as well as exploratory evaluations of PK/PD will be provided.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|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|
|IDH1 act mut||intrahepatic cholangiocarcinoma||predicted - sensitive||Olutasidenib||Phase Ib/II||Actionable||In a Phase I/II trial, Rezlidhia (olutasidenib) treatment demonstrated acceptable safety and preliminary clinical activity in patients with IDH1-mutant intrahepatic cholangiocarcinoma, and led to stable disease in 23% (6/23) of the evaluable patients (J Clin Oncol 38, no. 5_suppl (May 28, 2020); NCT03684811).||detail...|
|IDH1 act mut||chondrosarcoma||predicted - sensitive||Olutasidenib||Phase Ib/II||Actionable||In a Phase I/II trial, Rezlidhia (olutasidenib) treatment demonstrated acceptable safety and preliminary clinical activity in patients with IDH1-mutant intrahepatic cholangiocarcinoma, and led to stable disease in 31% (4/13) of evaluable patients (J Clin Oncol 38, no. 5_suppl (May 28, 2020); NCT03684811).||detail...|