Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
Profile Name | NOTCH1 mutant |
Gene Variant Detail | |
Relevant Treatment Approaches |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
NOTCH1 mutant | mantle cell lymphoma | predicted - resistant | Ibrutinib + Venetoclax | Phase II | Actionable | In a Phase II trial (AIM), distinct molecular profiles were identified in mantle cell lymphoma patients responded to Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy compared to those did not respond, with all patients harboring mutations in NSD2 (n=4), UBR5 (n=3), KMT2D (n=3), and 12 of 13 patients harboring mutations in ATM responded to the therapy, while SMARCA4 (n=4), CCND1 (n=2), and NOTCH1 (n=3) alterations were exclusively observed in nonresponders (PMID: 30455436; NCT02471391). | 30455436 | |
NOTCH1 mutant | chronic lymphocytic leukemia | decreased response | Chlorambucil + Ofatumumab | Phase III | Actionable | In a Phase III trial (COMPLEMENT1), the addition of Arzerra (ofatumumab) to Chlorambucil treatment in patients with chronic lymphocytic leukemia was associated with increased benefit to median progression-free survival (mPFS) in patients with wild-type NOTCH1 (mPFS 23.8 mo with ofatumumab vs.13.3 mo without, HR 0.50, CI 95% 0.39-0.63, p<0.01), but did not result in significant mPFS benefit in patients with mutant NOTCH1 (17.2 vs.13.1 mo, HR 0.81, CI 95% 0.50-1.31, p=0.45) (PMID: 31919090; NCT00748189). | 31919090 | |
NOTCH1 mutant | triple-receptor negative breast cancer | sensitive | PF-03084014 | Preclinical - Pdx | Actionable | In a preclinical study, PF-03084014 treatment resulted in tumor regression in patient-derived xenograft models of triple receptor negative breast cancer harboring NOTCH1 mutations (PMID: 25564152). | 25564152 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT02784795 | Phase I | Cisplatin + Gemcitabine + LY3039478 Carboplatin + Gemcitabine + LY3039478 LY3023414 + LY3039478 Abemaciclib + LY3039478 LY3039478 + Taladegib LY3039478 LY3023414 | A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors | Completed | USA | 3 |
NCT04660045 | Phase II | Acalabrutinib | Early Intervention With Acalabrutinib in Patients With High Risk CLL | Not yet recruiting | USA | 0 |
NCT02869633 | Phase II | Ibrutinib | Ibrutinib in Treating Patients With Refractory or Relapsed Lymphoma After Donor Stem Cell Transplant | Active, not recruiting | USA | 0 |
NCT03204188 | Phase II | Fludarabine + Ibrutinib + Pembrolizumab | Ibrutinib, Fludarabine, and Pembrolizumab in High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Recruiting | USA | 0 |