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DRUG:

KT-413

i
Other names: KT-413, KTX-120, IRAKIMiD
Company:
Kymera Therap
Drug class:
IKZF1 degrader, IKZF3 degrader, IRAK-4 degrader
9d
Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients with Relapsed or Refractory B-cell NHL (clinicaltrials.gov)
P1, N=7, Completed, Kymera Therapeutics, Inc. | Suspended --> Completed | N=80 --> 7
Trial completion • Enrollment change
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KT-413
6ms
Discovery of KT-413, a Targeted Protein Degrader of IRAK4 and IMiD Substrates Targeting MYD88 Mutant Diffuse Large B-Cell Lymphoma. (PubMed, J Med Chem)
KT-413 achieves concurrent degradation of these proteins by functioning as both a heterobifunctional degrader and a molecular glue. Based on the demonstrated activity and safety of KT-413 in preclinical studies, a phase 1 clinical trial in B-cell lymphomas, including MYD88 mutant ABC DLBCL, is currently underway.
Journal
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IKZF1 (IKAROS Family Zinc Finger 1) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
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KT-413
12ms
Trial completion date • Trial primary completion date
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KT-413
1year
Trial suspension
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KT-413
over1year
PHASE 1 TRIAL OF KT-413, A DEGRADER OF IRAK4 AND IMID SUBSTRATES, IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN’S LYMPHOMAS (ICML 2023)
Initial clinical data with KT-413 demonstrate degradation of IRAK4 and Ikaros/Aiolos in PBMC and tumor. It is anticipated that higher doses will achieve the predicted degradation profile in tumors that may confer clinical benefit in MYD88-mutant patients. Dose escalation is ongoing, and analyses from additional patients will be presented at the meeting.
Clinical • P1 data
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IKZF1 (IKAROS Family Zinc Finger 1) • IRF4 (Interferon regulatory factor 4) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
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MYD88 mutation • MYD88 wild-type
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KT-413
2years
Phase 1 Study of KT-413, a Targeted Protein Degrader of IRAK4 and IMiD Substrates, in Adult Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (ASH 2022)
Furthermore, based on new genetic classifications, co-mutations in MYD88 and CD79 (C5 and MCD subgroups) are associated with an inferior survival after standard R-CHOP. Enrollment in the Phase 1a portion of the KT413-DL-101 study is ongoing. NCT05233033.
Clinical • P1 data • IO biomarker
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IKZF1 (IKAROS Family Zinc Finger 1) • IRF4 (Interferon regulatory factor 4) • IL1R1 (Interleukin 1 receptor, type I) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
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MYD88 mutation • MYD88 mutation + CD79B mutation • MYD88 wild-type
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Rituxan (rituximab) • KT-413
2years
Precision Targeting of MYD88 Mutant DLBCL Using the Novel Combination of Irakimids and BCL2 Inhibition (ASH 2022)
Background: Based on new genetic classifications, co-mutations in MYD88 and CD79B (C5 and MCD subgroups) are associated with an inferior survival after standard R-CHOP. Preclinical studies highlight the potential of IRAKIMiDs as a therapeutic approach for the treatment of MYD88MT DLBCL. KTX-582 demonstrates preferential activity in MYD88MT ABC-DLBCL. Single agent venetoclax demonstrated varying potency in ABC-DLBCL cell lines, irrespective of MYD88 mutational status.
IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IKZF1 (IKAROS Family Zinc Finger 1) • CD79B (CD79b Molecule) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
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MYD88 mutation • BCL2 expression • CD79B mutation • MYD88 mutation + CD79B mutation • MYD88 wild-type
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Venclexta (venetoclax) • Rituxan (rituximab) • KT-413 • KTX-582