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Profile Name | RET rearrange |
Gene Variant Detail | |
Relevant Treatment Approaches | RET Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
RET rearrange | lung adenocarcinoma | predicted - sensitive | RET Inhibitor | Cabozantinib | Phase II | Actionable | In a Phase II trial, treatment with Cometriq (cabozantinib) resulted in an overall response rate of 28% (7/25) in patients with RET-rearranged lung adenocarcinoma, with a median duration of response of 7.0 months (PMID: 27825636; NCT01639508). | 27825636 |
RET rearrange | thyroid gland papillary carcinoma | sensitive | RET Inhibitor | Ponatinib | Preclinical | Actionable | In a preclinical study, Iclusig (ponatinib) decreased proliferation of papillary thyroid carcinoma cells harboring the RET/PTC1 rearrangement in culture (PMID: 23526464). | 23526464 |
RET rearrange | Advanced Solid Tumor | sensitive | RET Inhibitor | RXDX-105 | Preclinical - Pdx | Actionable | In a preclinical study, CEP-32496 (RXDX-105) induced tumor regression in patient-derived xenograft models of several advanced solid tumor type with RET rearrangements (2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; Abstract A174). | detail... |
RET rearrange | lung non-small cell carcinoma | predicted - sensitive | RET Inhibitor | RXDX-105 | Phase I | Actionable | In a Phase Ib trial, treatment with RXDX-105 (CEP-32496) resulted in an overall response rate of 19% (6/31) and stable disease in 39% (12/31) of patients with treatment-naive non-small cell lung cancer harboring a RET fusion (PMID: 30487236; NCT01877811) | 30487236 |
RET rearrange | lung non-small cell carcinoma | predicted - sensitive | RET Inhibitor | RXDX-105 | Case Reports/Case Series | Actionable | In a clinical case study, a patient with non-small cell lung cancer harboring a RET rearrangement demonstrated a sustained partial response following treatment with RXDX-105 (CEP-32496) on a Phase Ib clinical trial (PMID: 28011461; NCT01877811). | 28011461 |
RET rearrange | lung non-small cell carcinoma | no benefit | RET Inhibitor | Ponatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, multikinase inhibitor treatment demonstrated suboptimal clinical efficacy in RET-rearranged non-small cell lung cancer patients with measurable baseline brain metastasis, with a confirmed intracranial response rate of 18% (2/11); Iclusig (ponatinib) treatment resulted in no intracranial response in 4 patients with evaluable brain metastasis (PMID: 30017832). | 30017832 |
RET rearrange | lung non-small cell carcinoma | sensitive | RET Inhibitor | Pralsetinib | Guideline | Actionable | Gavreto (pralsetinib) is included in guidelines as a first-line therapy for non-small cell lung cancer patients with RET rearrangements (NCCN.org). | detail... |
RET rearrange | lung non-small cell carcinoma | sensitive | RET Inhibitor | Vandetanib | Clinical Study | Actionable | In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 18% (2/11, all partial responses) and stable disease in 27% (3/11) of patients following Caprelsa (vandetanib) treatment (PMID: 28447912). | 28447912 |
RET rearrange | lung non-small cell carcinoma | sensitive | RET Inhibitor | Vandetanib | Phase II | Actionable | In a Phase II trial, treatment with Caprelsa (vandetanib) resulted in an objective response rate of 18% (3/17, all partial responses) and disease control rate of 65% (stable disease in 47% (8/17) + partial response in 18% (3/17)) and median progression-free survival of 4.5 months in patients with RET-rearranged metastatic or recurrent non-small cell lung cancer (PMID: 27803005; NCT01823068). | 27803005 |
RET rearrange | thyroid gland papillary carcinoma | sensitive | RET Inhibitor | Sorafenib | Preclinical | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and activation of downstream signaling, and decreased growth of papillary thyroid carcinoma cells harboring the RET/PTC1 oncogene in culture (PMID: 17664273). | 17664273 |
RET rearrange | lung non-small cell carcinoma | sensitive | RET Inhibitor | Cabozantinib | Guideline | Actionable | Cometriq (cabozantinib) is in guidelines for non-small cell lung cancer patients with RET rearrangements (NCCN.org). | detail... |
RET rearrange | lung non-small cell carcinoma | sensitive | RET Inhibitor | Cabozantinib | Clinical Study | Actionable | In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 37% (7/19), with complete response in 5% (1/19) and partial response in 32% (6/19) of patients, and stable disease in 26% (5/19) of patients following Cometriq (cabozantinib) treatment (PMID: 28447912). | 28447912 |
RET rearrange | lung adenocarcinoma | no benefit | RET Inhibitor | Sunitinib | Clinical Study - Cohort | Actionable | In a Phase II trial, Sutent (sunitinib) treatment demonstrated limited clinical efficacy, with no objective responses and stable disease in 71% (5/7) of lung adenocarcinoma patients harboring RET rearrangements (PMID: 32312893; NCT01829217). | 32312893 |
RET rearrange | lung non-small cell carcinoma | predicted - sensitive | RET Inhibitor | Sunitinib | Clinical Study | Actionable | In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 18% (2/9, all partial responses), and stable disease in 33% (3/9) of patients following Sutent (sunitinib) treatment (PMID: 28447912). | 28447912 |
RET rearrange | lung non-small cell carcinoma | predicted - sensitive | RET Inhibitor | Alectinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Alecensa (alectinib) treatment resulted an intracranial response in 1 of 2 patients with RET-rearranged non-small cell lung cancer (PMID: 30017832). | 30017832 |
RET rearrange | lung non-small cell carcinoma | predicted - sensitive | RET Inhibitor | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, Alecensa (alectinib) treatment resulted in objective radiographic response in 50% (2/4) and stable disease in 25% (1/4) of non-small cell lung carcinoma patients harboring RET rearrangement (PMID: 27544060). | 27544060 |
RET rearrange | lung non-small cell carcinoma | sensitive | RET Inhibitor | Selpercatinib | Guideline | Actionable | Retevmo (selpercatinib) is in guidelines for non-small cell lung cancer patients with RET rearrangements (NCCN.org). | detail... |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT04984811 | Phase II | Atezolizumab + NT-I7 | NT-I7 in Combination With Atezolizumab in Previously Untreated, PD-L1-expressing, Locally Advanced or Metastatic NSCLC | Recruiting | USA | 0 |
NCT03178552 | Phase II | Entrectinib Carboplatin + Cisplatin + Gemcitabine Atezolizumab Carboplatin + Cisplatin + Pemetrexed Disodium Atezolizumab + Cobimetinib + Vemurafenib Alectinib | A Study to Evaluate Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (B-FAST) | Recruiting | USA | ITA | FRA | ESP | DEU | CAN | BEL | 21 |
NCT05215340 | Phase III | Pembrolizumab Datopotamab Deruxtecan + Pembrolizumab | Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (TROPION-Lung08) | Recruiting | USA | 1 |
NCT04131543 | Phase II | Cabozantinib | Phase II Study With Cabozantinib in Patients With RET Positive NSCLC (CRETA) | Recruiting | ITA | 0 |
NCT01877811 | Phase Ib/II | RXDX-105 | CEP-32496 in Patients With Advanced Solid Tumors in Phase 1 and Advanced Melanoma and Metastatic Colorectal Cancer in Phase 2 | Completed | USA | 0 |
NCT01877083 | Phase II | Lenvatinib | Study of the Safety and Activity of Lenvatinib (E7080) in Subjects With KIF5B-RET-Positive Adenocarcinoma of the Lung | Completed | USA | 4 |
NCT02867592 | Phase II | Cabozantinib | Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors | Active, not recruiting | USA | 0 |
NCT03175224 | Phase Ib/II | Bozitinib | APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA) | Recruiting | USA | ITA | FRA | ESP | CAN | 9 |
NCT03255083 | Phase I | DS-1205c + Osimertinib | DS-1205c With Osimertinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer | Terminated | 1 | |
NCT03468985 | Phase II | Cabozantinib + Nivolumab Cabozantinib + Ipilimumab + Nivolumab Nivolumab | Nivolumab, Cabozantinib S-Malate, and Ipilimumab in Treating Patients With Recurrent Stage IV Non-small Cell Lung Cancer | Active, not recruiting | USA | 0 |
NCT02193152 | Phase I | Pazopanib | Pazopanib in Molecularly Selected Patients With Advanced NSCLC | Terminated | USA | 0 |
NCT05153408 | Phase Ib/II | BLU-701 BLU-701 + Osimertinib BLU-701 + Carboplatin + Pemetrexed Disodium | (HARMONY) Study of BLU-701 in EGFR-mutant NSCLC | Recruiting | USA | 0 |
NCT02299141 | Phase I | Nintedanib | Nintedanib in Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer | Active, not recruiting | USA | 0 |
NCT01813734 | Phase II | Ponatinib | Ponatinib in Advanced NSCLC w/ RET Translocations | Completed | USA | 0 |
NCT04211337 | Phase III | Vandetanib Cabozantinib Selpercatinib | A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531) | Recruiting | USA | ITA | FRA | ESP | DEU | CAN | BEL | 14 |
NCT05064280 | Phase II | Lenvatinib Pembrolizumab | Phase II Study of Pembrolizumab in Combination With Lenvatinib in Patients With TNBC, NSCLC, and Other Tumor Types and Brain Metastases | Recruiting | USA | 0 |
NCT05048797 | Phase III | Cisplatin + Pembrolizumab + Pemetrexed Disodium Carboplatin + Pembrolizumab + Pemetrexed Disodium Trastuzumab deruxtecan | A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations | Recruiting | USA | ITA | FRA | ESP | DEU | CAN | BEL | AUT | 12 |
NCT03194893 | Phase III | Crizotinib Alectinib | A Roll Over Study of Alectinib in Patients With Anaplastic Lymphoma Kinase (ALK)-Positive or Rearranged During Transfection (RET)-Positive Cancer | Active, not recruiting | USA | ITA | FRA | ESP | 5 |
NCT05255302 | Phase II | Pembrolizumab + Pemetrexed Disodium Cisplatin + Paclitaxel + Pembrolizumab Carboplatin + Paclitaxel + Pembrolizumab | De-escalation Immunotherapy mAintenance Duration Trial for Stage IV Lung Cancer Patients With Disease Control After Chemo-immunotherapy Induction (DIAL) | Not yet recruiting | FRA | 0 |
NCT01831726 | Phase II | Dovitinib | Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib | Completed | USA | 0 |
NCT05313009 | Phase Ib/II | Sotorasib + TH-4000 | Tarlox and Sotorasib in Patients With KRAS G12C Mutations | Recruiting | USA | 0 |
NCT03037385 | Phase Ib/II | Pralsetinib | Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors (ARROW) | Active, not recruiting | USA | ITA | FRA | ESP | DEU | BEL | 7 |
NCT01829217 | Phase II | Sunitinib | Sunitinib in Never-Smokers With Lung Adenocarcinoma | Completed | USA | 0 |
NCT03131206 | Phase Ib/II | Alectinib | A Study of Alectinib in RET-rearranged Non-small Cell Lung Cancer or RET-mutated Thyroid Cancer | Terminated | USA | 0 |