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 | CDK12 inact mut |
Gene Variant Detail | |
Relevant Treatment Approaches | Olaparib |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
CDK12 inact mut | prostate cancer | sensitive | Olaparib | Olaparib | Guideline | Actionable | Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in CDK12 (NCCN.org). | detail... |
CDK12 inact mut | prostate cancer | sensitive | Olaparib | Olaparib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring CDK12 mutations (5.09 vs 2.20 mo) (PMID: 32343890; NCT02987543). | detail... 32343890 detail... |
CDK12 inact mut | prostate cancer | sensitive | Olaparib | Olaparib | Phase II | Actionable | In a Phase II (TOPARP-B) trial, Lynparza (olaparib) treatment resulted in a composite overall response rate of 25.0% (5/20) and a RECIST objective response rate of 0% (0/18) in patients with castration-resistant prostate cancer harboring deleterious CDK12 mutations (PMID: 31806540; NCT01682772). | 31806540 |
CDK12 inact mut | prostate cancer | predicted - sensitive | Abiraterone + Niraparib + Prednisone | Phase III | Actionable | In a Phase III trial (MAGNITUDE), Zejula (niraparib) in combination with Zytiga (abiraterone) and Adasone (prednisone) (AAP) significantly improved radiographic progression-free survival (16.5 vs 13.7 mo, HR 0.73, p=0.0217) compared to placebo and AAP in patients with metastatic castration-resistant prostate cancer harboring alterations in homologous recombination repair genes including ATM, BRCA1/2, BRIP1, CHEK2, FANCA, HDAC2, and PALB2 (J Clin Oncol 40, 2022 (suppl 6; abstr 12); NCT03748641). | detail... | |
CDK12 inact mut | prostate cancer | no benefit | Rucaparib | Phase II | Actionable | In a Phase II trial (TRITON2), activity of Rubraca (rucaparib) was limited in the cohort of patients with metastatic castrate-resistant prostate cancer harboring a CDK12 mutation presumed to be inactivating, with no confirmed radiographic responses in 10 evaluable patients and a PSA response in 1 patient with biallelic CDK12 alterations in the overall population of 15 patients, and a clinical benefit rate of 20% (3/15) at 6 months and 7.1% (1/14) at 12 months (PMID: 32086346; NCT02952534). | 32086346 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT04053322 | Phase II | Durvalumab + Fulvestrant + Olaparib | Durvalumab, With Olaparib and Fulvestrant in Advanced ER+, HER2- Breast Cancer Patients. (DOLAF) | Recruiting | FRA | 0 |
NCT03840967 | Phase II | Niraparib | A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma | Recruiting | USA | 0 |
NCT05071209 | Phase Ib/II | BAY1895344 | Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors | Recruiting | USA | 0 |
NCT03047135 | Phase II | Olaparib | Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis | Recruiting | USA | 0 |
NCT02734004 | Phase Ib/II | Durvalumab + Olaparib Bevacizumab + Durvalumab + Olaparib | A Phase I/II Study of MEDI4736 in Combination With Olaparib in Patients With Advanced Solid Tumors. (MEDIOLA) | Completed | USA | FRA | 5 |
NCT04019964 | Phase II | Nivolumab | Nivolumab in Biochemically Recurrent dMMR Prostate Cancer | Recruiting | USA | 0 |
NCT04985721 | Phase II | Pamiparib + Tislelizumab | A Trial of Pamiparib With Tislelizumab in Patients With Advanced Tumours With Homologous Recombination Repair Defects (IMPARP-HRD) | Recruiting | 1 | |
NCT04272645 | Phase II | Abemaciclib + Atezolizumab Abemaciclib Atezolizumab | Abemaciclib With or Without Atezolizumab in Metastatic Castration Resistant Prostate Cancer | Withdrawn | USA | 0 |
NCT04336943 | Phase II | Durvalumab + Olaparib | Durvalumab and Olaparib for the Treatment of Prostate Cancer in Men Predicted to Have a High Neoantigen Load | Recruiting | USA | 0 |
NCT04826341 | Phase Ib/II | Berzosertib + Sacituzumab govitecan-hziy | A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors | Recruiting | USA | 0 |
NCT05011383 | Phase II | Testosterone | High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT) | Recruiting | USA | 0 |
NCT04104893 | Phase II | Pembrolizumab | A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP) | Recruiting | USA | 0 |
NCT04019327 | Phase Ib/II | Talazoparib + Temozolomide | A Study of the Drugs Talazoparib and Temozolomide in Prostate Cancer | Recruiting | USA | 0 |
NCT04276376 | Phase II | Atezolizumab + Rucaparib | Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors (ARIANES) | Recruiting | FRA | 0 |
NCT04550494 | Phase II | Talazoparib | Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations | Recruiting | USA | 0 |
NCT04751929 | Phase II | Abemaciclib + Atezolizumab Atezolizumab Abemaciclib | Abemaciclib With or Without Atezolizumab for mCRPC | Recruiting | USA | 0 |
NCT03786796 | Phase II | Olaparib | Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (ORCHID) | Recruiting | USA | 0 |
NCT03810105 | Phase II | Durvalumab + Olaparib | A Study of Olaparib and Durvalumab in Prostate Cancer | Active, not recruiting | USA | 0 |
NCT04266912 | Phase Ib/II | Avelumab + Berzosertib | Avelumab and M6620 for the Treatment of DDR Deficient Metastatic or Unresectable Solid Tumors | Recruiting | USA | 0 |
NCT05010096 | Phase I | BAY1895344 + Copanlisib | BAY1895344 and Copanlisib for the Treatment of Molecularly Selected Patients With Advanced Solid Tumors | Withdrawn | 0 | |
NCT04983745 | Phase II | Dostarlimab-gxly + Niraparib | Niraparib and Dostarlimab in HRD Solid Tumors (DIDO) | Not yet recruiting | USA | 0 |
NCT05188508 | Phase II | Olaparib + Pembrolizumab + Temozolomide | Pembrolizumab, Olaparib, and Temozolomide for People With Glioma | Recruiting | USA | 0 |