Molecular Profile Detail

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Profile Name TP53 inact mut
Gene Variant Detail

TP53 inact mut (loss of function)

Relevant Treatment Approaches p53 Activator p53 Gene Therapy

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
TP53 inact mut chronic lymphocytic leukemia predicted - sensitive AZD6482 Preclinical Actionable In a preclinical study, AZD6482 induced cell death in TP53-deficient chronic lymphocytic leukemia cells in culture and inhibited tumor growth in xenograft models (PMID: 26563132). 26563132
TP53 inact mut prostate cancer no benefit Abiraterone Clinical Study - Cohort Actionable In a clinical study, treatment with either Xtandi (enzalutamide) or Zytiga (abiraterone) in patients with metastatic castration-resistant prostate cancer harboring a TP53 inactivating mutation, detected via circulating tumor cells, demonstrated a shorter progression-free survival (3.0 vs 8.7mo; P<0.0001) and overall survival (7.8 vs 26.7mo; P<0.0001) and fewer patients with a PSA response greater than or equal to 50% (15.4 vs 46.8%; P=0.008) compared to those patients with wild-type TP53 (PMID: 30209161). 30209161
TP53 inact mut breast carcinoma predicted - sensitive CHIR-124 + Irinotecan Preclinical - Cell line xenograft Actionable In a preclinical study, sequential treatment with Camptosaur (irinotecan) and CHIR-124 enhanced tumor growth inhibition compared to either agent alone in a breast carcinoma cell line xenograft model with defective TP53 (PMID: 17255282). 17255282
TP53 inact mut breast cancer sensitive AMG 900 Preclinical Actionable In a preclinical study, breast cancer cell lines with TP53 loss of function mutations had more pronounced apoptosis after treatment with AMG 900 in culture (PMID: 24091768). 24091768
TP53 inact mut breast carcinoma predicted - sensitive CHIR-124 + SN-38 Preclinical - Cell culture Actionable In a preclinical study, SN-38 and CHIR-124 demonstrated synergy in a breast carcinoma cell line with defective TP53, resulting in increased cell cycle arrest and apoptosis in culture (PMID: 17255282). 17255282
TP53 inact mut breast cancer sensitive Adavosertib + Radiotherapy Preclinical Actionable In a preclinical study, Adavosertib (MK-1775) increased the efficacy of radiation in breast cancer cells with defective TP53 in culture (PMID: 21799033). 21799033
TP53 inact mut ovarian carcinoma sensitive p53 Activator ReACp53 Preclinical Actionable In a preclinical study, ReACp53 induced cell death and decreased proliferation of ovarian carcinoma cells harboring TP53 mutations in culture, but did not effect viability of ovarian carcinoma cells with wild-type TP53 (PMID: 26748848). 26748848
TP53 inact mut ovarian cancer sensitive Adavosertib + Carboplatin + Paclitaxel Phase I Actionable In a Phase I trial, treatment with Adavosertib (MK-1775) plus Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in an improved progression-free survival by enhanced RECIST of 7.9 mo vs. 7.3 mo with placebo plus chemotherapy, and complete response in 11/9% (7/59) vs. 8.9% (5/62), partial response in 62.7% (37/59) vs. 61.3% (38/62), and stable disease in 5.1% (3/59) vs. 4.8% (3/62) of patients with platinum-sensitive ovarian cancer harboring an inactivating TP53 mutation (PMID: 32611648; NCT01357161) 32611648
TP53 inact mut lung non-small cell carcinoma not predictive Osimertinib Clinical Study - Cohort Actionable In a retrospective analysis, patients with non-small cell lung cancer harboring inactivating TP53 mutations at treatment discontinuation of Tagrisso (osimertinib) had shorter time to treatment discontinuation (5 vs 11.5 months, p=0.0005) compared to patients with wild-type TP53 (PMID: 31839416). 31839416
TP53 inact mut chronic lymphocytic leukemia sensitive Ceralasertib + Ibrutinib Preclinical Actionable In a preclinical study, AZD6738 sensitized TP53-deficient chronic lymphocytic leukemia cells to Imbruvica (Ibrutinib) treatment in culture (PMID: 26563132). 26563132
TP53 inact mut ovarian cancer sensitive Cisplatin + LB-100 Preclinical Actionable In a preclinical study, LB100 treatment decreased PP2A activity and increased sensitivity to Platinol (cisplatin) in a cisplatin-resistant ovarian cancer cell line harboring a TP53 inactivating mutation in culture (PMID: 25376608). 25376608
TP53 inact mut prostate cancer no benefit Enzalutamide Clinical Study - Cohort Actionable In a clinical study, treatment with either Xtandi (enzalutamide) or Zytiga (abiraterone) in patients with metastatic castration-resistant prostate cancer harboring a TP53 inactivating mutation, detected via circulating tumor cells, demonstrated a shorter progression-free survival (3.0 vs 8.7mo; P<0.0001) and overall survival (7.8 vs 26.7mo; P<0.0001) and fewer patients with a PSA response greater than or equal to 50% (15.4 vs 46.8%; P=0.008) compared to those patients with wild-type TP53 (PMID: 30209161). 30209161
TP53 inact mut lung small cell carcinoma sensitive p53 Activator APR-246 Preclinical - Cell line xenograft Actionable In a preclinical study, APR-246 induced apoptosis in small-cell lung cancer (SCLC) cell lines and decreased tumor growth in SCLC cell line xenograft models harboring Tp53 inactivating mutations (PMID: 21415220). 21415220
TP53 inact mut ovarian cancer sensitive Cisplatin + Nutlin-3a Preclinical Actionable In a preclinical study, Nutlin-3 and cisplatin worked cooperatively to induce apoptosis in ovarian cancer cell lines with TP53 inactivating mutations in culture (PMID: 25964101). 25964101
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT03654716 Phase I ALRN-6924 + Cytarabine ALRN-6924 Phase 1 Study of the Dual MDM2/MDMX Inhibitor ALRN-6924 in Pediatric Cancer Recruiting USA 0
NCT04049539 Phase II CPX-351 Vyxeos for Re-induction Treatment of Acute Myeloid Leukemia Patients With Persistent Disease After Induction Unknown status USA 0
NCT04419389 Phase Ib/II APR-246 + Ibrutinib APR-246 + Rituximab + Venetoclax APR-246 + Ibrutinib + Rituximab + Venetoclax APR-246 in Combination With Ibrutinib or Venetoclax-R in Subjects With TP53-Mutant R/R Non Hodgkin Lymphomas (NHL) (R/R) Active, not recruiting USA 0
NCT04155840 Phase II Bendamustine + Copanlisib + Rituximab Bendamustine and Rituximab in Combination With Copanlisib for the Treatment of Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Terminated USA 0
NCT03144804 Phase II Lamivudine A Phase 2 Study of Lamivudine in Patients With p53 Mutant Metastatic Colorectal Cancer Active, not recruiting USA 0
NCT01097278 Phase 0 Cholecalciferol S0812 High Dose Cholecalciferol in Premenopausal Women at High-Risk for Breast Cancer Completed USA 0
NCT04778397 Phase III Cytarabine + Idarubicin Azacitidine + Venetoclax Azacitidine + Hu5F9-G4 Cytarabine + Daunorubicin Study to Evaluate the Safety and Efficacy of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Previously Untreated Adults With TP53 Mutant Acute Myeloid Leukemia (ENHANCE-2) Recruiting USA 3