Newest OncoKB updates: July 12, 2023

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Dear OncoKB user,

Here are the latest OncoKB updates:

July 12, 2023Data version: v4.6

• Changed level of evidence

  Gene	Mutation	Cancer Type	Drug(s)	Previous Level	Current Level	Reason
  FGFR2	Oncogenic Mutations	Cholangiocarcinoma	RLY-4008 (Level 3A); Erdafitinib and AZD4547 (Currently Level 4)	4	3A	Abstract: Borad et al. Abstract# 4009, ASCO 2023
  IDH1	R132	Oligodendroglioma	Ivosidenib	3A	2	Inclusion in CNS NCCN Guidelines v1.2023; PMID: 32530764

• Updated therapeutic implications - new alterations with a level of evidence

  Level	Gene	Mutation	Cancer Type	Drug(s)	Evidence
  1	ATR	Oncogenic Mutations	Prostate Cancer	Talazoparib + Enzalutamide	FDA-approval of Talazoparib + Enzalutamide; PMID: 37285865
  1	FANCA
  1	MLH1
  1	MRE11
  1	NBN
  2	IDH1	Oncogenic Mutations	Oligodendroglioma	Ivosidenib	Inclusion in CNS NCCN Guidelines v1.2023; PMID: 32530764
  3A	IDH2	R172	Oligodendroglioma, Astrocytoma	Vorasidenib	PMID: 37272516
  4	KRAS	G12	All Solid Tumors	RMC-6236	Abstract: Koltun et al. Abstract# 3597, AACR 2022
  4	FGFR2	Amplification	All Solid Tumors	RLY-4008	Abstract: Borad et al. Abstract# 4009, ASCO 2023

• Updated therapeutic implications - Addition of therapies for variants with a level of evidence

  Gene	Mutation	Cancer Type	Current Level of Evidence	Drug(s) currently in OncoKB	Drug(s) added to OncoKB	Evidence
  ALK	Fusions	Inflammatory Myofibroblastic Tumors	1	Crizotinib (Level 1); Brigatinib, Lorlatinib, Ceritinib (Level 2)	Alectinib (Level 2)	Inclusion in Soft Tissue Sarcoma NCCN Guidelines v2.2023
  FGFR2	Fusions	Cholangiocarcinoma	1	Futibatinib, Pemigatinib (Level 1)	RLY-4008 (Level 3A)	Abstract: Borad et al. Abstract# 4009, ASCO 2023
  BRCA1	Oncogenic Mutations	Prostate Cancer	1	Olaparib, Rucaparib (Level 1)	Talazoparib + Enzalutamide (Level 1)	FDA-approval of Talazoparib + Enzalutamide; PMID: 37285865
  					Olaparib + Abiraterone + Prednisone/Prednisolone (Level 1)	FDA-approval of Olaparib + Abiraterone + Prednisone/Prednisolone; Abstract: Clarke et al. Abstract# LBA16, ASCO GUCS 2023
  BRCA2	Oncogenic Mutations	Prostate Cancer	1	Olaparib, Rucaparib (Level 1)	Talazoparib + Enzalutamide (Level 1)	FDA-approval of Talazoparib + Enzalutamide; PMID: 37285865
  					Olaparib + Abiraterone + Prednisone/Prednisolone (Level 1)	FDA-approval of Olaparib + Abiraterone + Prednisone/Prednisolone; Abstract: Clarke et al. Abstract# LBA16, ASCO GUCS 2023
  ATM	Oncogenic Mutations	Prostate Cancer	1	Olaparib (Level 1)	Talazoparib + Enzalutamide (Level 1)	FDA-approval of Talazoparib + Enzalutamide; PMID: 37285865
  PALB2
  CDK12
  CHEK2
  RAD51C
  IDH1	R132	Oligodendroglioma, Astrocytoma	3A	Ivosidenib	Vorasidenib (Level 3A)	PMID: 37272516
  FGFR2	Oncogenic Mutations	All Solid Tumors	4	Erdafitinib and AZD4547 (Level 4)	RLY-4008 (Level 4)	Abstract: Borad et al. Abstract# 4009, ASCO 2023
  KRAS	G12D	All Solid Tumors	4	RMC-6236	MRTX-1133 and ASP3082 (level 4)	Abstract: Nagashima et al. Abstract# 5735, AACR 2023; PMID: 36472553

• Updated therapeutic implications - Removal of therapies for variants with a level of evidence

  Gene	Mutation	Cancer Type	Current Level of Evidence	Drug(s) currently in OncoKB	Drug(s) removed from OncoKB	Evidence
  FGFR1	Amplification	Lung Squamous Cell Carcinoma	3A	Erdafitinib	Debio1347	Failed in basket study - no further clinical development
  FGFR1, FGFR2, FGFR3	Oncogenic Mutations	All Solid Tumors	4	Erdafitinib, AZD4547

• Addition of 4 new genes:
  CADCHD4H4C6TRIB3

As always, don’t hesitate to reach out if you have comments, questions or suggestions. We love to hear from you.

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The OncoKB Team