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Profile Name CDKN2A loss
Gene Variant Detail

CDKN2A loss (loss of function)

Relevant Treatment Approaches CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
CDKN2A loss melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line with CDKN2A loss demonstrated sensitivity to Mekinist (trametinib) in culture, resulting in inhibition of cell growth (PMID: 27488531). 27488531
CDKN2A loss melanoma sensitive CDK Inhibitor (Pan) CDK4 Inhibitor CDK6 Inhibitor Alvocidib Preclinical Actionable In a preclinical study, melanoma cell lines with CDKN2A loss demonstrated a greater sensitivity to Alvocidib (flavopiridol) as compared to melanoma cell lines positive for CDKN2A (PMID: 12777976). 12777976
CDKN2A loss neuroendocrine tumor sensitive CDK4 Inhibitor ZK 304709 Preclinical Actionable In a preclinical study, an orthotopic mouse model treated with ZK 304709 demonstrated an 80% tumor growth reduction in neuroendocrine tumor cells with CDKN2A loss (PMID: 18829975). 18829975
CDKN2A loss lung squamous cell carcinoma predicted - sensitive CDK4/6 Inhibitor Palbociclib Clinical Study - Cohort Actionable In a Phase II trial (NLMT), Ibrance (palbociclib) treatment resulted in an observed objective response rate (ORR) of 0% (0/19), durable clinical benefit rate (DCBR) of 22% (4/18), and medial progression-free survival (PFS) of 4.2 months in patients with lung squamous cell carcinoma harboring CDKN2A loss, with Bayesian estimated OR and DCBR of 3% and 24%, respectively, and Bayesian predictive probability of success for PFS >0.99 (PMID: 32669708, NCT02664935). 32669708
CDKN2A loss lung adenocarcinoma predicted - sensitive CDK4/6 Inhibitor Palbociclib Clinical Study - Cohort Actionable In a Phase II trial (NLMT), Ibrance (palbociclib) treatment resulted in an observed objective response rate (ORR) of 4% (1/27), durable clinical benefit rate (DCBR) of 27.5% (8/29), and medial progression-free survival (PFS) of 3.3 months in patients with lung adenocarcinoma harboring CDKN2A loss, with Bayesian estimated OR and DCBR of 6% and 29%, respectively, and Bayesian posterior probability for PFS of 0.69 (PMID: 32669708, NCT02664935). 32669708
CDKN2A loss biliary tract cancer no benefit CDK4/6 Inhibitor Palbociclib Phase II Actionable In a Phase II trial (TAPUR), patients with biliary cancer harboring a CDKN2A mutation or loss of CDKN2A (n=10) did not demonstrate an objective response or stable disease at 16 weeks when treated with single therapy, Ibrance (palbociclib), demonstrating a median progression-free survival of 7.3 weeks and an overall survival of 11.1 weeks (JCO Precision Oncology, Aug 14, 2019; NCT02693535). detail...
CDKN2A loss chordoma sensitive CDK4/6 Inhibitor Abemaciclib Preclinical - Cell culture Actionable In a preclinical study, Abemaciclib (LY2835219) inhibited growth of chordoma cell lines with CDKN2A loss and loss of p16 protein expression in culture (PMID: 26183925). 26183925
CDKN2A loss melanoma resistant CDK4/6 Inhibitor Palbociclib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line deficient for CDKN2A demonstrated resistance to treatment with Ibrance (palbociclib) in culture (PMID: 27488531). 27488531
CDKN2A loss pancreatic cancer no benefit CDK4/6 Inhibitor Palbociclib Phase II Actionable In a Phase II trial (TAPUR), patients with pancreatic cancer harboring a CDKN2A mutation or loss of CDKN2A (n=10) did not demonstrate an objective response or stable disease at 16 weeks when treated with single therapy, Ibrance (palbociclib), demonstrating a median progression-free survival of 7.2 weeks and an overall survival of 12.4 weeks (JCO Precision Oncology, Aug 14, 2019; NCT02693535). detail...
CDKN2A loss Advanced Solid Tumor predicted - sensitive PF-00477736 + PF3644022 Preclinical - Cell culture Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of multiple cancer cell lines harboring CDKN2A loss and in Cdkn2a-depleted transformed cells in culture (PMID: 26140595). 26140595
CDKN2A loss lung non-small cell carcinoma predicted - sensitive CDK4/6 Inhibitor Palbociclib Phase II Actionable In a Phase II trial (TAPUR), Ibrance (palbociclib) treatment resulted in a disease control rate of 29% (7/28, 1 partial response, 6 stable disease at 16 weeks) in patients with non-small cell lung cancer harboring CDKN2A loss or mutations, with a median progression-free survival of 9.7 weeks and a median overall survival of 20.6 months (J Clin Oncol 37, 2019 (suppl; abstr 9041); NCT02693535). detail...
CDKN2A loss lung non-small cell carcinoma predicted - sensitive CDK4/6 Inhibitor Palbociclib Phase II Actionable In a Phase II trial, treatment with Ibrance (palbociclib) resulted in stable disease in 50% (8/16) of non-small cell lung cancer patients with CDKN2A loss (J Clin Oncol 32:5s, 2014 (suppl; abstr 8077)). detail...
CDKN2A loss pancreatic cancer decreased response CDK4/6 Inhibitor HMN-214 + Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the activity of HMN-214 in pancreatic cancer cell lines with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss renal cell carcinoma sensitive CDK4/6 Inhibitor Palbociclib Preclinical Actionable In a preclinical study, renal cell carcinoma cell lines with CDKN2A loss were sensitive to Palbociclib (PD-0332991) (PMID: 23898052). 23898052
CDKN2A loss pancreatic cancer decreased response CDK4/6 Inhibitor GSK461364 + Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the efficacy of GSK461364 in pancreatic cancer cells with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss pancreatic cancer decreased response CDK4/6 Inhibitor Gemcitabine + Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the efficacy of Gemzar (gemcitabine) in pancreatic cancer cells with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss chordoma sensitive CDK4/6 Inhibitor Palbociclib Preclinical - Cell culture Actionable In a preclinical study, Ibrance (palbociclib) inhibited expression of phosphorylated Rb and growth of chordoma cell lines with CDKN2A loss and loss of p16 protein expression in culture (PMID: 26183925). 26183925
CDKN2A loss brain glioblastoma multiforme sensitive CDK4 Inhibitor Milciclib Preclinical - Cell line xenograft Actionable In a preclinical study, Milciclib (PHA-848125AC) resulted in tumor regression in glioma cell line xenograft models with CDKN2A loss (PMID: 23347136). 23347136
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT03110744 Phase II Palbociclib CDK4/6 Inhibition in Locally Advanced/Metastatic Chordoma (NCT-PMO-1601) Recruiting 1
NCT01711658 Phase II Cisplatin + Lapatinib + Radiotherapy Cisplatin + Radiotherapy TRYHARD: Radiation Therapy Plus Cisplatin With or Without Lapatinib in Treating Patients With Head and Neck Cancer. (TRYHARD) Active, not recruiting USA | CAN 0
NCT02933736 Phase 0 Ribociclib Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients Recruiting USA 0
NCT02896335 Phase II Palbociclib Palbociclib In Progressive Brain Metastases Recruiting USA 0
NCT04040205 Phase II Abemaciclib Abemaciclib for Bone and Soft Tissue Sarcoma With Cyclin-Dependent Kinase (CDK) Pathway Alteration Recruiting USA 0
NCT03834740 Phase I Everolimus + Ribociclib A Phase 0 /II Study of Ribociclib (LEE011) in Combination With Everolimus in Preoperative Recurrent High-Grade Glioma Patients Scheduled for Resection Recruiting USA 0
NCT02523014 Phase II Abemaciclib GSK2256098 Vismodegib Capivasertib Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas Recruiting USA 0
NCT02693535 Phase II Cobimetinib + Vemurafenib Regorafenib Ipilimumab + Nivolumab Palbociclib Afatinib Talazoparib Pembrolizumab Temsirolimus Pertuzumab + Trastuzumab Crizotinib Abemaciclib Sunitinib Olaparib TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer Recruiting USA 0
NCT02334527 Phase II Palbociclib Phase II Trial of Palbociclib (PD-0332991) in Patients With Metastatic Urothelial Cancer (UC) After Failure of First-Line Chemotherapy Terminated USA 0
NCT04391595 Phase I Abemaciclib + LY3214996 LY3214996 Plus Abemaciclib in Recurrent Glioblastoma Patients Recruiting USA 0
NCT03435250 Phase I AG-270 + Docetaxel AG-270 + Gemcitabine + Nab-paclitaxel AG-270 Study of AG-270 in Participants With Advanced Solid Tumors or Lymphoma With MTAP Loss Recruiting USA 2
NCT02540876 Phase I ABT-348 Ilorasertib in Treating Patients With CDKN2A-deficient Advanced or Metastatic Solid Cancers That Cannot Be Removed by Surgery Completed USA 0
NCT03220646 Phase II Abemaciclib Abemaciclib (LY2835219) in Patients With Recurrent Primary Brain Tumors Active, not recruiting USA 0