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| ID | Type | Description | Link |
|---|---|---|---|
| CO40778 | Other Identifier | Hoffmann-La Roche | |
| 2023-505088-35-00 | EU Trial (CTIS) Number |
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This is an open-label, Phase 1/2 multicenter dose escalation study in pediatric patients with relapsed or refractory extracranial solid tumors (Phase 1), with additional expansion cohorts (Phase 2) in patients with primary brain tumors harboring NTRK1/2/3 or ROS1 gene fusions, and extracranial solid tumors harboring NTRK1/2/3 or ROS1 gene fusions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Extracranial solid tumors harboring NTRK1/2/3, | Active Comparator | Arm closed for further enrollment ROS1, ALK non-gene fusion molecular alterations Oral entrectinib (RXDX-101) |
|
| CNS tumors harboring- NTRK1/2/3, ROS1, ALK | Active Comparator | Arm closed for further enrollment molecular alterations, including gene fusions Oral entrectinib (RXDX-101) |
|
| Neuroblastoma | Active Comparator | Arm closed for further enrollment Oral entrectinib (RXDX-101) |
|
| Non-neuroblastoma, extracranial solid tumors | Active Comparator | Arm closed for further enrollment harboring - NTRK1/2/3, ROS1, ALK gene fusions Oral entrectinib (RXDX-101) |
|
| Any participant unable to swallow capsules | Active Comparator | Arm closed for further enrollment Any participant who otherwise meet all other eligibility criteria Oral entrectinib (RXDX-101) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entrectinib | Drug | TRKA/B/C, ROS1, and ALK inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Assessed by National Cancer Institute Common Terminology for Adverse Events Criteria (NCI CTCAE v4.03) | Approximately 6 months |
| Recommended Phase 2 Dose (RP2D) of F1 Formulation In Pediatric Participants Able To Swallow Intact Capsules | Assessed by NCI CTCAE v4.03 | Approximately 6 months |
| Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric Participants Able To Swallow Intact Capsules | Assessed by NCI CTCAE v4.03 | Approximately 6 months |
| Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric In Participants Dosed Via Feeding Tube (Nasogastric Tube Or Gastric Tube) | Assessed by NCI CTCAE v4.03 | Approximately 6 months |
| Recommended Phase 2 Dose (RP2D) Of Minitablets/F15 Formulation In Pediatric Participants Unable To Swallow Intact Capsules | Assessed by NCI CTCAE v4.03 | Approximately 6 months |
| Cohort B: Objective Response Rate (ORR) | Assessed by RANO per the BICR | Approximately 6 months |
| Cohort D: ORR | Assessed by RECIST v1.1 per the BICR | Approximately 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability - AE, ECG and Labs assessed by NCI CTCAE v4.03 | AE, ECG and Labs assessed by NCI CTCAE v4.03 | Approximately 24 months |
| Maximum observed plasma drug concentration (Cmax) using F1 Formulation |
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Inclusion Criteria:
Disease status:
Phase 1 portion (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1
Phase 2 portion:
Tumor type:
Phase 1 portion:
* Part A: Relapsed or refractory extracranial solid tumors
Phase 2 portion
Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse
Archival tumor tissue from diagnosis or, preferably, at relapse
Performance status: Lansky or Karnofsky score ≥ 60% and minimum life expectancy of at least 4 weeks
Prior therapy: Participants must have a disease that is locally advanced, metastatic, or where surgical resection is likely to result in severe morbidity, and who have no satisfactory treatment options for solid tumors and primary CNS tumors that are neurotrophic tyrosine receptor kinase (NTRK) or ROS1 fusion-positive
Participants must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment
Adequate organ and neurologic function
Females of childbearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation. Agreement to remain abstinent or use use combined contraceptive methods prior to study entry, for the duration of study participation and in the following 90 days after discontinuation of study treatment.
For male participants with a female partner of childbearing potential or a pregnant female partner: Agreement to remain abstinent or use a condom during the treatment period and for at least 3 months after the last dose of study drug
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Diego | La Jolla | California | 92093-0706 | United States | ||
| UCSF Benioff Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40086048 | Derived | Desai AV, Bagchi A, Armstrong AE, van Tilburg CM, Basu EM, Robinson GW, Wang H, Casanova M, Andre N, Campbell-Hewson Q, Wu Y, Cardenas A, Ci B, Ryklansky C, Devlin CE, Meneses-Lorente G, Wulff J, Hutchinson KE, Gajjar A, Fox E. Efficacy and safety of entrectinib in children with extracranial solid or central nervous system (CNS) tumours harbouring NTRK or ROS1 fusions. Eur J Cancer. 2025 May 2;220:115308. doi: 10.1016/j.ejca.2025.115308. Epub 2025 Feb 22. | |
| 35395680 |
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For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing.
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| Expansion: CNS tumors harboring NTRK1/2/3, ROS1 |
| Active Comparator |
gene fusions Oral entrectinib (RXDX-101) |
|
| Expansion: Extracranial solid tumors harboring NTRK1/2/3, ROS1 | Active Comparator | NTRK 1,2,3 and ROS1 fusions Oral entrectinib (RXDX-101) |
|
|
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
| Approximately 24 months |
| Maximum observed plasma drug concentration (Cmax) using F06 Formulation given intact | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Maximum observed plasma drug concentration (Cmax) using F06 Formulation administered via feeding tube | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Maximum observed plasma drug concentration (Cmax) using minitablets/F15 | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Time to Cmax, by inspection (Tmax) using F1 Formulation | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Time to Cmax, by inspection (Tmax) using F06 Formulation given intact | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Time to Cmax, by inspection (Tmax) using F06 Formulation administered via feeding tube | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Time to Cmax, by inspection (Tmax) using minitablets/F15 | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| AUC at steady state (AUCss) using F1 Formulation | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| AUC at steady state (AUCss) using F06 Formulation given intact | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| AUC at steady state (AUCss) using F06 Formulation administered via feeding tube | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| AUC at steady state (AUCss) using minitablets/F15 | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Terminal half life (t½) using F1 Formulation | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Terminal half life (t½) using F06 Formulation given intact | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Terminal half life (t½) using F06 Formulation administered via feeding tube | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Terminal half life (t½) using minitablets/F15 | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Area under the drug concentration by time curve (AUC) using F1 Formulation | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Area under the drug concentration by time curve (AUC) using F06 Formulation given intact | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Area under the drug concentration by time curve (AUC) using F06 Formulation administered via feeding tube | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Area under the drug concentration by time curve (AUC) using minitablets/F15 | Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter | Approximately 24 months |
| Cohort A, D, or E: Clinical Benefit Rate (CBR) | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Cohort B or E: CBR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Cohort C: CBR | Assessed by the Curie scale per the BICR and investigator | Approximately 6 months |
| Cohort A, D, or E: Progression-free Survival (PFS) | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Cohort B or E: PFS | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Cohort C: PFS | Assessed by the Curie scale per the BICR and investigator | Approximately 6 months |
| Cohort A, D, or E: Overall Survival (OS) | Assessed by RECIST v1.1 | Approximately 6 months |
| Cohort B or E: OS | Assessed by RANO | Approximately 6 months |
| Cohort A, D, or E: ORR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Cohort B or E: ORR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Cohort C: ORR | Assessed by the Curie scale per the BICR and investigator | Approximately 6 months |
| Cohort A, D, or E: Time to response (TTR) | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Cohort B or E: TTR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Cohort C: TTR | Assessed by the Curie scale per the BICR and investigator | Approximately 6 months |
| Cohort A, D, or E: Duration of Response (DOR) | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Cohort B or E: DOR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Cohort C: DOR | Assessed by the Curie scale per the BICR and investigator | Approximately 6 months |
| Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): ORR | Assessed by RANO per the investigator | Approximately 6 months |
| Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): ORR | Assessed by RECIST v1.1 per the investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): ORR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): ORR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): ORR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): ORR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): ORR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): ORR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): DOR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): DOR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): DOR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): DOR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): DOR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): DOR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): DOR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): DOR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): TTR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): TTR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): TTR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): TTR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): TTR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): TTR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): TTR | Assessed by RECIST v1.1 per the BICR and investigator | Approximately 6 months |
| Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): TTR | Assessed by RANO per the BICR and investigator | Approximately 6 months |
| San Francisco |
| California |
| 94158 |
| United States |
| Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
| Egleston Children's Hospital at Emory University Atlanta | Atlanta | Georgia | 30322 | United States |
| University of Chicago | Chicago | Illinois | 60637 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21205 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Washington University,St. Louis Children's Hospital | St Louis | Missouri | 63110 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| Oregon Health & Science Uni | Portland | Oregon | 97239 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| St. Jude Children'S Research Hospital | Memphis | Tennessee | 38105 | United States |
| Texas Children's Cancer and Hematology Center | Houston | Texas | 77030 | United States |
| Primary Children's Hospital | Salt Lake City | Utah | 84113 | United States |
| The Hospital for Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
| Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine | Shanghai | Shanghai Municipality | 200082 | China |
| Beijing Children's Hospital, Capital Medical University | Beijing | China |
| Centre Leon Berard | Lyon | 69373 | France |
| Hôpital de la Timone, Oncologie Pédiatrique | Marseille | 13385 | France |
| Universitaetsklinikum Heidelberg | Heidelberg | Baden-Wurttemberg | 69120 | Germany |
| Hong Kong Children's Hospital | Hong Kong | 00000 | Hong Kong |
| Fondazione IRCCS Istituto Nazionale dei Tumori | Milan | Lombardy | 20133 | Italy |
| Hospital Infantil Universitario Nino Jesus | Madrid | 28009 | Spain |
| Royal Marsden Hospital (Sutton) | London | SW3 6JJ | United Kingdom |
| Royal Victoria Infirmary | Newcastle upon Tyne | NE1 4LP | United Kingdom |
| Derived |
| Desai AV, Robinson GW, Gauvain K, Basu EM, Macy ME, Maese L, Whipple NS, Sabnis AJ, Foster JH, Shusterman S, Yoon J, Weiss BD, Abdelbaki MS, Armstrong AE, Cash T, Pratilas CA, Corradini N, Marshall LV, Farid-Kapadia M, Chohan S, Devlin C, Meneses-Lorente G, Cardenas A, Hutchinson KE, Bergthold G, Caron H, Chow Maneval E, Gajjar A, Fox E. Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG). Neuro Oncol. 2022 Oct 3;24(10):1776-1789. doi: 10.1093/neuonc/noac087. |
| 31838007 | Derived | Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL Jr, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD; trial investigators. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):271-282. doi: 10.1016/S1470-2045(19)30691-6. Epub 2019 Dec 11. |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D012008 | Recurrence |
| D009362 | Neoplasm Metastasis |
| D009447 | Neuroblastoma |
| D018201 | Nephroma, Mesoblastic |
| D001932 | Brain Neoplasms |
| D012509 | Sarcoma |
| D012512 | Sarcoma, Ewing |
| D005910 | Glioma |
| D012468 | Salivary Gland Neoplasms |
| D000077273 | Thyroid Cancer, Papillary |
| D008527 | Medulloblastoma |
| D009396 | Wilms Tumor |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009385 | Neoplastic Processes |
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D018193 | Neoplasms, Complex and Mixed |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D012516 | Osteosarcoma |
| D018213 | Neoplasms, Bone Tissue |
| D009372 | Neoplasms, Connective Tissue |
| D009062 | Mouth Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D012466 | Salivary Gland Diseases |
| D000231 | Adenocarcinoma, Papillary |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D013964 | Thyroid Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004700 | Endocrine System Diseases |
| D013959 | Thyroid Diseases |
| D009386 | Neoplastic Syndromes, Hereditary |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C000607349 | entrectinib |
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