Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

NCT03037385 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: BO428632016-004390-41BLU-667-1101
• Study Type: interventional
• Target: 590
• Locations: 13 countries
• Sites: 71

Brief Summary

This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of pralsetinib (BLU-667) administered orally in participants with medullary thyroid cancer (MTC), RET-altered NSCLC and other RET-altered solid tumors.

Conditions

RET-altered Non Small Cell Lung Cancer; Medullary Thyroid Cancer; RET-altered Papillary Thyroid Cancer; RET-altered Colon Cancer; RET-altered Solid Tumors; Lung Neoplasm; Carcinoma, Non-Small-Cell Lung; Thyroid Diseases; Thyroid Neoplasm; Thyroid Cancer, Papillary; Carcinoma, Neuroendocrine; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Disease; Carcinoma, Bronchogenic; Bronchial Neoplasms; Endocrine System Diseases; Endocrine Gland Neoplasm; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Colonic Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasm; Digestive System Disease; Gastrointestinal Disease; Colonic Diseases; Intestinal Disease

Keywords

RET Lung; RET Thyroid; RET fusion; RET alteration; RET mutation; RET positive; RET inhibitor; RET altered; RET rearrangement; RET NSCLC; RET medullary thyroid cancer; RET-rearranged NSCLC; RET-rearranged thyroid; M918T; TRIM33-RET; RET fusion lung cancer; RET fusion thyroid cancer; lung cancer mutation; BLU 667; RET tyrosine kinase; RET gene mutation; RET kinase; RET MTC; advanced lung cancer; advanced non small cell lung cancer; metastatic lung cancer; KIF5B-RET; CCDC6-RET; NCOA4-RET; advance solid tumor; V804L; V804M; thyroid cancer RET inhibitor; lung cancer RET inhibitor; RET PTC; rearranged during transfection; RET-PTC1; RET-PTC; RET-PTC3; RET-PTC4; PRKAR1A-RET; RET-PTC2; GOLGA5-RET; RET-PTC5; ERC1-RET; KTN1-RET; RET-PTC8; HOOK3-RET; PCM1-RET; TRIM24-RET; RET-PTC6; TRIM27-RET; RET-PTC7; AKAP13-RET; FKBP15-RET; SPECC1L-RET; TBL1XR1-RET; BCR-RET; FGRF1OP-RET; RFG8-RET

Outcome Measures

Primary Outcomes (3)

• Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib

  MTD was defined as the highest tolerated dose of pralsetinib without causing dose limiting toxicities (DLTs). DLT was defined as any Grade ≥3 adverse event (AE) occurring during Cycle 1 during Phase 1 (dose escalation) that is not clearly caused by something other than pralsetinib. RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase.

  Up to approximately 30.8 months

• Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs)

  An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.

  From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years)

• Phase 2: Overall Response Rate (ORR)

  ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) for at least two assessments with at least 28 days apart and no disease progression (PD) in between. Per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), were presented.

  Up to approximately 79.8 months

Secondary Outcomes (41)

• Phase 1: ORR

  Up to approximately 28 months

• Phase 1 and Phase 2: ORR in RET-fusion Positive NSCLC Participants With Specific RET Gene Status

  Up to approximately 79.8 months

• Phase 1 and Phase 2: ORR in RET-mutation MTC Participants With Specific RET Gene Status

  Up to approximately 79.8 months

• Phase 1 and Phase 2: ORR in RET-fusion Positive TC Participants With Specific RET Gene Status

  Up to approximately 79.8 months

• Phase 1 and Phase 2: Clinical Benefit Rate (CBR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status

  Up to approximately 79.8 months

Study Arms (2)

Phase 1 Dose Escalation

EXPERIMENTAL

Multiple doses of pralsetinib (BLU-667) for oral administration.

Drug: pralsetinib (BLU-667)

Phase 2 Dose Expansion

EXPERIMENTAL

Oral dose of pralsetinib (BLU-667) as determined during Dose Escalation.

Drug: pralsetinib (BLU-667)

Interventions

pralsetinib (BLU-667) DRUG

pralsetinib (BLU-667) is a potent and selective inhibitor of the RET mutations, fusions, and predicted resistant mutants

Also known as: BLU-667

Phase 1 Dose Escalation; Phase 2 Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis during dose escalation (Phase 1) - Pathologically documented, definitively diagnosed non-resectable advanced solid tumor.
• All participants treated at doses \> 120 mg per day must have MTC, or a RET-altered solid tumor per local assessment of tumor tissue and/or blood.
• Diagnosis during dose expansion (Phase 2) - All participants (with the exception of participants with MTC enrolled in Groups 3, 4, and 9) must have an oncogenic RET-rearrangement/fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor, as determined by local or central testing of tumor or circulating tumor nucleic acid in blood; as detailed below.
• Group 1 - participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion previously treated with a platinum-based chemotherapy.
• Group 2 - participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion not previously treated with a platinum-based chemotherapy, including those who have not had any systemic therapy. Prior platinum chemotherapy in the neoadjuvant and adjuvant setting is permitted if the last dose of platinum was 4 months or more before the first dose of study drug.
• Group 3 - participants must have pathologically documented, definitively diagnosed advanced MTC that had progressed within 14 months prior to the Screening Visit and was previously treated with cabozantinib and/or vandetanib.
• Group 4 - participants must have pathologically documented, definitively diagnosed advanced MTC that had progressed within 14 months prior to the Screening Visit and was not previously treated with cabozantinib and/or vandetanib.
• Group 5 - participants must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion, have previously received standard of care (SOC) appropriate for their tumor type (unless there is no accepted standard therapy for the tumor type or the Investigator has determined that treatment with standard therapy is not appropriate), and must not have been eligible for any of the other groups.
• Group 6 - participants must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion or mutation that was previously treated with a selective tyrosine kinase inhibitor (TKI) that inhibits RET
• Group 7 - participants must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET mutation previously treated with SOC appropriate for the tumor type and not eligible for any of the other groups
• Group 8 - participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion that was previously treated with a platinum based chemotherapy (China only).
• Group 9 - participants must have pathologically documented, definitively diagnosed advanced MTC that had progressed within 14 months prior to the Screening Visit, and was not previously treated with systemic therapy (except prior cytotoxic chemotherapy is allowed) for advanced or metastatic disease (China only).
• Participants must have non-resectable disease.
• Dose expansion (Phase 2): Participants in all groups (except Group 7) must have measurable disease per RECIST v1.1 (or RANO, criteria if appropriate for tumor type).
• Participants agrees to provide tumor tissue (archived, if available or a fresh biopsy) for RET status confirmation and is willing to consider an on-treatment tumor biopsy, if considered safe and medically feasible by the treating Investigator. For Phase 2, Group 6, participants are required to undergo a pretreatment biopsy to define baseline RET status in tumor tissue.

You may not qualify if:

• Participant's cancer has a known primary driver alteration other than RET. For example, NSCLC with a targetable mutation in EGFR, ALK, ROS1 or BRAF; colorectal with an oncogenic KRAS, NRAS, or BRAF mutation.
• Participants had any of the following within 14 days prior to the first dose of study drug:
• Platelet count \< 75 × 10\^9/L.
• Absolute neutrophil count \< 1.0 × 10\^9/L.
• Hemoglobin \< 9.0 g/dL (red blood cell transfusion and erythropoietin may be used to reach at least 9.0 g/dL, but must have been administered at least 2 weeks prior to the first dose of study drug.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 × the upper limit of normal (ULN) if no hepatic metastases are present; \> 5 × ULN if hepatic metastases are present.
• Total bilirubin \> 1.5 × ULN; \> 3 × ULN with direct bilirubin \> 1.5 × ULN in presence of Gilbert's disease.
• Estimated (Cockcroft-Gault formula) or measured creatinine clearance \< 40 mL/min.
• Total serum phosphorus \> 5.5 mg/dL
• QT interval corrected using Fridericia's formula (QTcF) \> 470 msec or history of prolonged QT syndrome or Torsades de pointes, or familial history of prolonged QT syndrome.
• Clinically significant, uncontrolled, cardiovascular disease.
• Central nervous system (CNS) metastases or a primary CNS tumor that is associated with progressive neurological symptoms.
• Clinically symptomatic interstitial lung disease or interstitial pneumonitis including radiation pneumonitis
• Participants in Groups 1-5 and 7 (Phase 2) previously treated with a selective RET inhibitor
• Participant had a major surgical procedure within 14 days of the first dose of study drug

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (71)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic-Jacksonville

Jacksonville, Florida, 32224, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136-1002, United States

Location

Maryland Oncology Hematology, P.A.

Columbia, Maryland, 21044-3257, United States

Location

Massachusetts General Hospital.

Boston, Massachusetts, 02114-2696, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-0934, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55902-3003, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110-1010, United States

Location

Albany Medical Center

Albany, New York, 12208-3412, United States

Location

Weill Cornell Medical College-New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Texas Oncology-Austin Midtown

Austin, Texas, 78705-1165, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4000, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Beijing Cancer Hospital

Beijing, 100036, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

The affiliated Cancer Hospital, School of Medicine, UESTC

Chengdu, 610041, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Chongqing Cancer Hospital

Chongqing, 400030, China

Location

Fujian Provincial Cancer Hospital

Fuzhou, 350014, China

Location

First Affiliated Hospital of Gannan Medical University

Ganzhou, 341000, China

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510060, China

Location

Guangdong General Hospital

Guangzhou, 510080, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Jinan Central Hospital

Jinan, 250013, China

Location

Gansu Cancer Hospital

Lanzhou, 730050, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjing, 300060, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430023, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

Institut Bergonie

Bordeaux, 33000, France

Location

Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez

Lille, 59037, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Centre Antoine Lacassagne

Nice, 6100, France

Location

Institut Curie

Paris, 75248, France

Location

CHU de Rennes - Hopital de Pontchaillo

Rennes, 35033, France

Location

Hôpital Larrey

Toulouse, 31059, France

Location

Gustave Roussy

Villejuif, 94800, France

Location

Helios Klinikum Emil von Behring GmbH

Berlin, 14165, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

Thoraxklinik Heidelberg gGmbH

Heidelberg, 69126, Germany

Location

Klinikum der Universität München

München, 81377, Germany

Location

Pius-Hospital

Oldenburg, 26121, Germany

Location

The Chinese University of Hong Kong

Shatin, 123456, Hong Kong

Location

Ospedale Santa Maria Delle Croci

Ravenna, Emilia-Romagna, 48100, Italy

Location

Istituto Nazionale Tumori Regina Elena

Rome, Lazio, 00144, Italy

Location

IEO

Milan, Lombardy, 20141, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, 20162, Italy

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 120-752, South Korea

Location

Institut Catala d Oncologia Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Guys and St Thomas NHS Foundation Trust, Guys Hospital

London, SE1 9RT, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, W1T 7HA, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (8)

• Subbiah V, Hu MI, Mansfield AS, Taylor MH, Schuler M, Zhu VW, Hadoux J, Curigliano G, Wirth L, Gainor JF, Alonso G, Adkins D, Godbert Y, Ahn MJ, Cassier PA, Cho BC, Lin CC, Zalutskaya A, Barata T, Trask P, Scalori A, Bordogna W, Heinzmann S, Brose MS. Pralsetinib in Patients with Advanced/Metastatic Rearranged During Transfection (RET)-Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study. Thyroid. 2024 Jan;34(1):26-40. doi: 10.1089/thy.2023.0363.

  PMID: 38009200 DERIVED

• Subbiah V, Burris HA 3rd, Kurzrock R. Revolutionizing cancer drug development: Harnessing the potential of basket trials. Cancer. 2024 Jan;130(2):186-200. doi: 10.1002/cncr.35085. Epub 2023 Nov 7.

  PMID: 37934000 DERIVED

• Griesinger F, Curigliano G, Subbiah V, Baik CS, Tan DS, Lee DH, Misch D, Garralda E, Kim DW, van der Wekken AJ, Gainor JF, Paz-Ares L, Liu SV, Kalemkerian GP, Bowles DW, Mansfield AS, Lin JJ, Smoljanovic V, Rahman A, Zalutskaya A, Louie-Gao M, Boral AL, Mazieres J. Pralsetinib in patients with RET fusion-positive non-small-cell lung cancer: A plain language summary of the ARROW study. Future Oncol. 2024 Feb;20(6):297-306. doi: 10.2217/fon-2023-0155. Epub 2023 Nov 2.

  PMID: 37916501 DERIVED

• Zhou Q, Zhao J, Chang J, Wang H, Fan Y, Wang K, Wu G, Nian W, Sun Y, Sun M, Wang X, Shi H, Zheng X, Yao S, Qin M, Shen Z, Yang J, Wu YL. Efficacy and safety of pralsetinib in patients with advanced RET fusion-positive non-small cell lung cancer. Cancer. 2023 Oct 15;129(20):3239-3251. doi: 10.1002/cncr.34897. Epub 2023 Jun 6.

  PMID: 37282666 DERIVED

• Subbiah V, Cassier PA, Siena S, Garralda E, Paz-Ares L, Garrido P, Nadal E, Vuky J, Lopes G, Kalemkerian GP, Bowles DW, Seetharam M, Chang J, Zhang H, Green J, Zalutskaya A, Schuler M, Fan Y, Curigliano G. Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. Nat Med. 2022 Aug;28(8):1640-1645. doi: 10.1038/s41591-022-01931-y. Epub 2022 Aug 12.

  PMID: 35962206 DERIVED

• Popat S, Liu SV, Scheuer N, Hsu GG, Lockhart A, Ramagopalan SV, Griesinger F, Subbiah V. Addressing challenges with real-world synthetic control arms to demonstrate the comparative effectiveness of Pralsetinib in non-small cell lung cancer. Nat Commun. 2022 Jun 17;13(1):3500. doi: 10.1038/s41467-022-30908-1.

  PMID: 35715405 DERIVED

• Subbiah V, Hu MI, Wirth LJ, Schuler M, Mansfield AS, Curigliano G, Brose MS, Zhu VW, Leboulleux S, Bowles DW, Baik CS, Adkins D, Keam B, Matos I, Garralda E, Gainor JF, Lopes G, Lin CC, Godbert Y, Sarker D, Miller SG, Clifford C, Zhang H, Turner CD, Taylor MH. Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study. Lancet Diabetes Endocrinol. 2021 Aug;9(8):491-501. doi: 10.1016/S2213-8587(21)00120-0. Epub 2021 Jun 9.

  PMID: 34118198 DERIVED

• Gainor JF, Curigliano G, Kim DW, Lee DH, Besse B, Baik CS, Doebele RC, Cassier PA, Lopes G, Tan DSW, Garralda E, Paz-Ares LG, Cho BC, Gadgeel SM, Thomas M, Liu SV, Taylor MH, Mansfield AS, Zhu VW, Clifford C, Zhang H, Palmer M, Green J, Turner CD, Subbiah V. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study. Lancet Oncol. 2021 Jul;22(7):959-969. doi: 10.1016/S1470-2045(21)00247-3. Epub 2021 Jun 9.

  PMID: 34118197 DERIVED

MeSH Terms

Conditions

Carcinoma, Medullary; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Thyroid Diseases; Thyroid Neoplasms; Thyroid Cancer, Papillary; Carcinoma, Neuroendocrine; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Colonic Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Multiple Endocrine Neoplasia Type 2a

Interventions

pralsetinib

Condition Hierarchy (Ancestors)

Neoplasms, Ductal, Lobular, and Medullary; Bronchial Diseases; Rectal Diseases; Multiple Endocrine Neoplasia; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Phase 1 (Complete): * Advanced MTC, NSCLC or other solid tumor * 30-600mg (PO QD or BID) Phase 2 (400mg QD): * Group 1: RET fusion NSCLC previously treated with a platinum chemotherapy * Group 2: RET fusion NSCLC not previously treated for metastatic disease * Group 3: MTC previously treated with cabozantinib and/or vandetanib * Group 4: MTC not previously treated with cabozantinib or vandetanib * Group 5: Other solid tumors with a RET fusion not eligible for any of the other groups and previously treated with SOC or have no acceptable SOC for their tumor type as determined by the investigator * Group 6: Any solid tumor with a RET alteration (fusion or mutation) previously treated with a selective RET Inhibitor * Group 7: Other solid tumors with a RET mutation previously treated with SOC * Group 8: RET fusion NSCLC previously treated with a platinum chemotherapy (China only) * Group 9: MTC not previously treated with systemic therapy for advanced or metastatic disease (China only)

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 31, 2017
• Study Start: March 17, 2017
• Primary Completion: March 21, 2024
• Study Completion: March 21, 2024
• Last Updated: May 31, 2025
• Results First Posted: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); BE (1); FR (8); DE (5); IT (4); SG (1); KR (4); NL (2); TW (2); GB (3); CN (17); HK (1); US (18)