OncoKB New Data Release - August 15, 2024

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Aug 15, 2024, 10:31:08 AM8/15/24

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Data Release v4.20

August 15, 2024

What's New

Updated Therapeutic Implications:

Level 3A: Lunresertib + Camonsertib added as a treatment for FBXW7 and PPP2R1A Oncogenic Mutations in endometrial and ovarian cancer based on preclinical and clinical trial data of lunresertib + camonsertib in patients with FBXW7-mutated and/or PPP2R1A-mutated gynecologic cancers and FDA fast track designation (PMID: 38410486; Abstract: Yap, T. et al., Abstract# 35396. AACR-NCI-EORTC 2023; Abstract: Gallo, D. et al., Abstract# B057, AACR 2023; Abstract: Yap, T. et al., Abstract# B156, AACR-NCI-EORTC 2023)

Level 4: Lunresertib + Camonsertib added as a treatment for FBXW7 and PPP2R1A Oncogenic Mutations in all solid tumors based on preclinical and clinical trial data of lunresertib + camonsertib in patients with FBXW7-mutated and/or PPP2R1A-mutated solid tumors (PMID: 38410486; Abstract: Yap, T. et al., Abstract# 35396. AACR-NCI-EORTC 2023; Abstract: Gallo, D. et al., Abstract# B057, AACR 2023; Abstract: Yap, T. et al., Abstract# B156, AACR-NCI-EORTC 2023)

Level 1: IDH1 R132C/H/G/S/L in oligodendroglioma promoted from Level 2 to Level 1 based on FDA approval of vorasidenib in patients with astrocytoma and oligodendroglioma with susceptible IDH1/2 mutations (PMID: 37272516)

Sensitivity-associated evidence currently in OncoKB™ for IDH1 R132 (Level 2 in oligodendroglioma; Ivosidenib)

Level 1: IDH1 R132C/H/G/S/L in astrocytoma promoted from Level 3A to Level 1 based on FDA approval of vorasidenib in patients with astrocytoma and oligodendroglioma with susceptible IDH1/2 mutations (PMID: 37272516)

Sensitivity-associated evidence currently in OncoKB™ for IDH1 R132 (Level 2 in oligodendroglioma; Ivosidenib [Promoted from Level 3A based on NCCN Central Nervous System Guidelines inclusion])

Level 3A: CCNE1 Amplification in endometrial and ovarian cancer promoted from Level 4 to Level 3A based on preclinical and clinical trial data of lunresertib + camonsertib in patients with CCNE1-amplified gynecologic cancers and FDA fast track designation (PMID: 38410486; Abstract: Yap, T. et al., Abstract# 35396. AACR-NCI-EORTC 2023; Abstract: Gallo, D. et al., Abstract# B057, AACR 2023; Abstract: Yap, T. et al., Abstract# B156, AACR-NCI-EORTC 2023)

Unleveled: SRSF2 and ZRSR2 Oncogenic Mutations in acute myeloid leukemia demoted from Level 4 to Unleveled based on discontinuation of H3B-8800 (RVT-2001) development (PMID: 34172893)

Addition of therapy(s) associated with a tumor type-specific leveled alteration(s) (without changing the alteration's highest level of evidence)

Level 3A: Inavolisib + Palbociclib + Fulvestrant added as a combination treatment for PIK3CA Oncogenic Mutations in breast cancer based on clinical trial data of inavolisib + palbociclib + fulvestrant in patients with PIK3CA-mutated, HR+/HER2- breast cancer and FDA breakthrough therapy designation (Abstract: Jhaveri, K. et al,. Abstract# GS03-13, SABCS 2023)

Sensitivity-associated evidence currently in OncoKB™ for PIK3CA C420R, E542K, H1047L/R/Y, R88Q, N345K, E545A/D/G/K/Q, Q546E/R/K/P, M1043V/I and G1049R (Level 1 in breast cancer; Capivasertib + Fulvestrant; Alpelisib + Fulvestrant [Level 1 for C420R, E542K, E545A/D/G/K, H1047Y/R/L, Q546E/R only]) and for PIK3CA Oncogenic Mutations (excluding Level 1 mutations listed above) (Level 2 in breast cancer; Alpelisib + Fulvestrant; Capivasertib + Fulvestrant)

Level 4: Lunresertib + Camonsertib added as a treatment for CCNE1 Amplification in all solid tumors based on preclinical and clinical trial data of lunresertib + camonsertib in patients with CCNE1-amplified solid tumors (PMID: 38410486; Abstract: Yap, T. et al., Abstract# 35396. AACR-NCI-EORTC 2023; Abstract: Gallo, D. et al., Abstract# B057, AACR 2023; Abstract: Yap, T. et al., Abstract# B156, AACR-NCI-EORTC 2023)

Sensitivity-associated evidence currently in OncoKB™ for CCNE1 Amplification (Level 4 in all solid tumors; Lunresertib, BLU-222 as single agents)

Level 4: Emavusertib added as a treatment for SF3B1 and U2AF1 Oncogenic Mutations in acute myeloid leukemia and myelodysplastic syndrome based on supporting clinical trial data of emavusertib in patients with SF3B1 and U2AF1-mutated acute myeloid leukemia and myelodysplastic syndrome (Abstract: Garcia-Manero, G. et al., Abstract# 7016, JCO, ASCO 2022)

Sensitivity-associated evidence currently in OncoKB™ for SF3B1 and U2AF1 Oncogenic Mutations (Level 4 in acute myeloid leukemia; H3B-8800 (RVT-2001) [Removed in this update based on discontinuation of H3B-8800 development (PMID: 34172893))

Level 4: Ceralasertib added as a treatment for SF3B1, U2AF1, SRSF2 and ZRSR2 Oncogenic Mutations in myelodysplastic syndrome and chronic myelomonocytic leukemia based on supporting clinical trial data of ceralasertib in patients with spliceosome factor-mutated myelodysplastic syndrome and chronic monomyelocytic leukemia (Abstract: Brunner, A. et al., Abstract# P758, HemaSphere, EHA 2022)

Sensitivity-associated evidence currently in OncoKB™ for SF3B1, U2AF1, SRSF2 and ZRSR2 Oncogenic Mutations (Level 4 in myelodysplastic syndrome and chronic monomyelocytic leukemia; H3B-8800 (RVT-2001) [Removed in this update based on discontinuation of H3B-8800 development (PMID: 34172893))

Gene Curation: