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Profile Name | CDKN2A del |
Gene Variant Detail | |
Relevant Treatment Approaches | CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
CDKN2A del | melanoma | decreased response | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, treatment with an immune checkpoint inhibitor resulted in a decreased response in melanoma patients with homozygous deletion of CDKN2A or loss of function CDKN2A mutations compared to patients with wild-type CDKN2A in one cohort, with a lower overall survival (OS) of 27.2 mo vs not yet reached and time to treatment failure of 10 vs 20.1 mo, respectively, but in a second cohort, there were no significant differences in OS (PMID: 34074656). | 34074656 | |
CDKN2A del | head and neck squamous cell carcinoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, homozygous deletion of CDKN2A or loss of function CDKN2A mutations in two cohorts of head and neck squamous cell carcinoma patients were not predictive of overall survival or time to treatment failure when treated with immune checkpoint inhibitors (PMID: 34074656). | 34074656 | |
CDKN2A del | gastrointestinal stromal tumor | no benefit | CDK4/6 Inhibitor | Palbociclib | Phase II | Actionable | In a Phase II trial, Ibrance (palbociclib) treatment did not demonstrated clinical efficacy in heavily pre-treated gastrointestinal stromal tumor patients harboring CDKN2A homozygous or heterozygous deletion, with 86.4% (19/22) of patients demonstrated progressive disease at 4 months (PMID: 30979737; NCT01907607). | 30979737 |
CDKN2A del | lung non-small cell carcinoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, homozygous deletion of CDKN2A or loss of function CDKN2A mutations in two cohorts of non-small cell lung cancer patients were not predictive of overall survival or time to treatment failure when treated with immune checkpoint inhibitors (PMID: 34074656). | 34074656 | |
CDKN2A del | gastroesophageal cancer | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, homozygous deletion of CDKN2A or loss of function CDKN2A mutations in one cohort of esophagogastric cancer patients were not predictive of overall survival or time to treatment failure when treated with immune checkpoint inhibitors, but in another cohort were significantly associated with reduced overall survival compared to wild-type CDKN2A (8 months vs 17 months, P=0.006) (PMID: 34074656). | 34074656 | |
CDKN2A del | renal cell carcinoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, homozygous deletion of CDKN2A or loss of function CDKN2A mutations in one cohort of renal cell carcinoma patients were not predictive of overall survival or time to treatment failure when treated with immune checkpoint inhibitors, but in another cohort were significantly associated with reduced overall survival compared to wild-type CDKN2A (13 months vs 50 months, P=0.002)(PMID: 34074656). | 34074656 | |
CDKN2A del | glioblastoma | sensitive | CDK4/6 Inhibitor | Palbociclib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Ibrance (palbociclib) inhibited proliferation of patient-derived glioblastoma cells harboring homozygous deletion of CDKN2A in culture and prolonged survival in patient-derived xenograft models (PMID: 22711607). | 22711607 |
CDKN2A del | lung cancer | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited tumor growth in cell line xenograft models of CDKN2A-deleted lung cancer (PMID: 26140595). | 26140595 | |
CDKN2A del | bladder urothelial carcinoma | decreased response | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, treatment with an immune checkpoint inhibitor resulted in a decreased response in urothelial carcinoma patients with either homozygous deletion of CDKN2A or loss of function CDKN2A mutations compared to those patients with wild-type CDKN2A in two different cohorts, with an overall survival for each cohort of 8.8 and 11 mo. versus 25.2 and 19 mo, respectively, and time to treatment failure of 4.2 mo. versus 8.4 mo., respectively, in one cohort (PMID: 34074656). | 34074656 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT04118036 | Phase II | Abemaciclib + Pembrolizumab | Abemaciclib + Pembrolizumab In Glioblastoma | Withdrawn | USA | 0 |
NCT02981940 | Phase II | Abemaciclib | A Study of Abemaciclib in Recurrent Glioblastoma | Recruiting | USA | 0 |
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 |
NCT04074785 | Phase I | Abemaciclib + Bevacizumab | Pilot Study of Abemaciclib With Bevacizumab in Recurrent Glioblastoma Patients With Loss of CDKN2A/B or Gain or Amplification of CDK4/6 | Active, not recruiting | USA | 0 |
NCT02478320 | Phase II | ABT-348 | Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors | Completed | USA | 0 |
NCT02546661 | Phase I | AZD9150 + Durvalumab Durvalumab + Selumetinib AZD4547 Durvalumab + Olaparib Durvalumab AZD4547 + Durvalumab Durvalumab + Vistusertib Adavosertib + Durvalumab | Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (BISCAY) | Active, not recruiting | USA | FRA | ESP | CAN | 1 |
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 | Active, not recruiting | USA | FRA | ESP | 0 |
NCT03356223 | Phase II | Abemaciclib | Evaluation of ABEMACICLIB Monotherapy in Patients With Locally Advanced/Metastatic Head and Neck Cancer After Failure of Platinum and Cetuximab or Anti-EGFR-based Therapy and Harboring an Homozygous Deletion of CDKN2A, and/or an Amplification of CCND1 and/or of CDK6 (ABORL) | Recruiting | FRA | 0 |
NCT03994796 | Phase II | Abemaciclib GDC-0084 Entrectinib | Genetic Testing in Guiding Treatment for Patients With Brain Metastases | Recruiting | USA | 0 |
NCT04116541 | Phase II | Alectinib Cabozantinib Ribociclib + Siremadlin | A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors. (MegaMOST) | Recruiting | FRA | 0 |
NCT04966481 | Phase III | Cetuximab + Palbociclib Cetuximab | Palbociclib and Cetuximab Versus Cetuximab Monotherapy for Patients With CDKN2A-altered, HPV-unrelated Head and Neck Squamous Cell Carcinoma Who Experienced Disease Progression on a PD-1/L1 Inhibitor | Recruiting | USA | 0 |