Molecular Profile Detail


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Profile Name RET mutant
Gene Variant Detail

RET mutant (unknown)

Relevant Treatment Approaches


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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET mutant thyroid gland medullary carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression free survival (60 vs 20 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RET mutations (PMID: 27525386). 27525386
RET mutant pheochromocytoma predicted - sensitive Sunitinib Case Reports/Case Series Actionable In a Phase II trial (SNIPP), a patient with pheochromocytoma harboring a germline RET mutation achieved a partial response to treatment with Sutent (sunitinib), and demonstrated a 64% reduction in tumor volume and remained on treatment for over 7 years (PMID: 31105270). 31105270
RET mutant thyroid gland medullary carcinoma sensitive Pralsetinib FDA approved Actionable In a Phase I/II trial (ARROW) that supported FDA approval, Gavreto (pralsetinib) treatment was well-tolerated, and resulted in an overall response rate (ORR) of 65% (51/79, 5% complete response, 59% partial response) in patients with advanced or metastatic medullary thyroid cancer harboring RET mutations, ORR was 60% (32/53) in patients with prior therapies and 74% (14/19) in treatment-naive patients (Ann Oncol. Vol 31, Supplement 4, S1084, Sep 1, 2020; NCT03037385). detail... detail...
RET mutant thyroid gland medullary carcinoma sensitive Everolimus Phase II Actionable In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, including patients harboring RET mutations, with median progression-free survival of 33 weeks (PMID: 26294908). 26294908
RET mutant thyroid gland medullary carcinoma sensitive Selpercatinib FDA approved Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 69% (38/55), with five complete and 33 partial responses, in adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations who were previously treated, while patients who had not been previously treated demonstrated an ORR of 73% (64/88), with ten complete and 54 partial responses (PMID: 32846061; NCT03157128). detail... 32846061
RET mutant colorectal cancer sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) demonstrated efficacy in RET mutant positive colorectal cancer cell lines (PMID: 23811235). 23811235
RET mutant lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was 44.9 mo in a patient harboring RET mutation, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). 30268448
RET mutant cancer sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited wild-type RET and RET mutations to prevent cell proliferation in cell culture (PMID: 17664273). 17664273
RET mutant Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) inhibited proliferation of cancer cell lines harboring RET mutations in cultured and in cell line xenograft models (PMID: 23526464). 23526464
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT04105270 Phase II Carboplatin + Durvalumab + Pemetrexed Disodium Cisplatin + Durvalumab + Pemetrexed Disodium Durvalumab P2 of RMT in Combo w Durvalumab or Durva + Chemo in Untreated Adenocarcinoma NSCLC Not yet recruiting USA 0
NCT03639714 Phase Ib/II GRT-C901 + GRT-R902 + Ipilimumab + Nivolumab A Study of a Personalized Neoantigen Cancer Vaccine Active, not recruiting USA 1
NCT03052569 Expanded access RXDX-105 Expanded Access to RXDX-105 for Cancers With RET Alterations No longer available USA 0
NCT04760288 Phase III Cabozantinib Pralsetinib Vandetanib A Study of Pralsetinib Versus Standard of Care (SOC) for Treatment of RET-Mutated Medullary Thyroid Cancer (MTC). (AcceleRET-MTC) Not yet recruiting USA | CAN 23
NCT03780517 Phase I DS-5010 Safety, Efficacy, and Tolerability of BOS172738 in Patients With Advanced Rearranged During Transfection (RET) Gene-Altered Tumors Active, not recruiting USA 6
NCT02299141 Phase I Nintedanib Nintedanib in Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer 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 | CAN 12
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) Recruiting USA 12
NCT03391869 Phase III Ipilimumab + Nivolumab Phase III Trial of (LCT) After Nivolumab and Ipilimumab Recruiting USA 0
NCT03157128 Phase Ib/II Selpercatinib Phase 1/2 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) Recruiting USA | CAN 14
NCT01896479 FDA approved Cabozantinib A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer Active, not recruiting CAN 13
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
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
NCT02193152 Phase I Pazopanib Pazopanib in Molecularly Selected Patients With Advanced NSCLC Terminated USA 0
NCT01831726 Phase II Dovitinib Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib Completed USA 0
NCT01396408 Phase II Temsirolimus Sunitinib A Phase II Study of Sunitinib or Temsirolimus in Patients With Advanced Rare Tumours Active, not recruiting CAN 0
NCT03934372 Phase Ib/II Ponatinib Safety and Efficacy of Ponatinib for Treatment of Pediatric Recurrent or Refractory Leukemias or Solid Tumors Active, not recruiting 7