IDH2 R172G

P2, N=145, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P2, N=94, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=94, Recruiting, National Cancer Institute (NCI) | Active, not recruiting --> Recruiting

P2, N=94, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024

One-, 3- and 5-year survival rates are 83%, 50%, and 43%, respectively. In all but 1 study, IST is associated with better outcomes than IDH2 wild-type tumors and SMARCB1-deficient sinonasal tumors.

P2, N=94, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

Using overlapping PCR, transfection, immunoblotting, immunoprecipitation, measurements of enzyme activity, glucose, lactic acid, ATP, and reactive oxygen species (ROS), cell viability, protein degradation assays post-inhibition of the 26S proteasome (bortezomib) or HSP90 (17-AAG), and a homology model, we demonstrated that the properties of ten cancer-associated IDH2 variants (R140G/Q/W and R172S/K/M/W/G/C/P) arising from point mutations are closely related to their structure and stability...The homology model further revealed that changes in conformation and IDH2 protein stability appeared to be associated with these point mutations. Taken together, our findings provide information important for understanding the molecular mechanisms of IDH2 mutations in tumors.

P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2022 --> Jul 2023 | Trial primary completion date: Jul 2022 --> Jul 2023

Olaparib was well tolerated in this pt population. The study did not meet the pre-specified response-based threshold for moving to step 2, but prolonged SD was observed in pts with grades 2 and 3 histologies, suggesting olaparib monotherapy could be of clinical benefit in select pts. Grade 4 tumors per the 2021 WHO classification defined by histology or CDKN2A mutation derived minimal to no benefit from this drug highlighting the usefulness of this new classification for future patient stratification and trial design and suggesting investigation of this treatment earlier in the disease course might be of interest.

In recent years the US Food and Drug Administration (FDA) has been very active in approving targeted therapeutic drugs for AML patients including Midostaurin (Rydapt; 2017) and Gilteritinib (Xospata;2018) for FLT3 mutations; Enasidenib (Idhifa; 2017) for IDH2 mutations and Ivosidenib (Tibsovo; 2018) for IDH1 mutations. The IDH1 CDx, IDH2 CDx and FLT3 CDx tests are highly sensitive and Versiti provides average turn around time of 3 business days which enable rapid decision making on the recently available drug therapies for AML patients. We strongly recommend that the IDH1 CDx, IDH2 CDx and FLT3 CDx tests should be performed on all AML patients for better care.

This study demonstrates that priming with oral azacitidine (CC486) in combination with CHOP as initial therapy is safe, effective, and produces sustained remission in PTCL-TFH subtype. Epigenetic priming with azacitidine appears to inhibit the proliferation of TFH lymphoma cells, providing potential synergistic mechanism of action with chemotherapy. This active combination will be further evaluated in the upcoming ALLIANCE/ US Intergroup randomized study A051902, comparing oral azacitidine-CHO(E)P vs duvelisib-CHO(E)P against CHO(E)P in CD30 negative PTCL.

In the present study, we report one case of carotid body PGL with a somatic mutation in the gene encoding isocitrate dehydrogenase 2 (IDH2). The missense mutation in IDH2 resulted in R172G amino acid substitution, which exhibits neomorphic activity and production of D-2-hydroxyglutarate.

P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2021 --> Jul 2022 | Trial primary completion date: Jul 2021 --> Jul 2022

P2, N=94, Recruiting, National Cancer Institute (NCI) | N=46 --> 94

P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2020 --> Jul 2021 | Trial primary completion date: Jul 2020 --> Jul 2021

P2, N=46, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Dec 2020 --> Dec 2022 | Trial primary completion date: Dec 2020 --> Dec 2022