Clinical trial NCT03037385: 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
Official title: A Phase 1/2 Study of the Highly-selective RET Inhibitor, BLU-667, in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-01-31
Enrollment: 590
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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)
Primary purpose: TREATMENT

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.

Detailed description: The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase 2). Both parts will enroll participants with advanced non-resectable NSCLC, advanced non-resectable thyroid cancer and other advanced solid tumors that have progressed following standard systemic therapy, have not adequately responded to standard systemic therapy, or the participants must be intolerant to or the Investigator has determined that treatment with standard therapy is not appropriate, or there must be no accepted standard therapy for their disease.

Eligibility criteria: Key Inclusion Criteria:

* 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.
* Participants has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.

Key Exclusion Criteria:

* 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:

  1. Platelet count \< 75 × 10\^9/L.
  2. Absolute neutrophil count \< 1.0 × 10\^9/L.
  3. 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.
  4. 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.
  5. Total bilirubin \> 1.5 × ULN; \> 3 × ULN with direct bilirubin \> 1.5 × ULN in presence of Gilbert's disease.
  6. Estimated (Cockcroft-Gault formula) or measured creatinine clearance \< 40 mL/min.
  7. 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
* Participant had a history of another primary malignancy that had been diagnosed or required therapy within the a year prior to the study
* Pregnant or breastfeeding female participants

Primary outcomes:
measure: Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib
timeFrame: Up to approximately 30.8 months
measure: Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs)
timeFrame: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years)
measure: Phase 2: Overall Response Rate (ORR)
timeFrame: Up to approximately 79.8 months
Secondary outcomes:
measure: Phase 1: ORR
timeFrame: Up to approximately 28 months
measure: Phase 1 and Phase 2: ORR in RET-fusion Positive NSCLC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: ORR in RET-mutation MTC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: ORR in RET-fusion Positive TC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: Clinical Benefit Rate (CBR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: CBR in RET-mutation MTC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: CBR in RET-fusion Positive TC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: Disease Control Rate (DCR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: DCR in RET-mutation MTC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: DCR in RET-fusion Positive TC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: Duration of Response (DOR) in RET-mutation NSCLC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: DOR in RET-mutation MTC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 1 and Phase 2: DOR in RET-fusion Positive TC Participants With Specific RET Gene Status
timeFrame: Up to approximately 79.8 months
measure: Phase 2: DOR
timeFrame: Up to approximately 79.8 months
measure: Phase 2: CBR
timeFrame: Up to approximately 79.8 months
measure: Phase 2: DCR
timeFrame: Up to approximately 79.8 months
measure: Phase 2: Progression-free Survival (PFS)
timeFrame: Up to approximately 7 years
measure: Phase 2: Overall Survival (OS)
timeFrame: Up to approximately 7 years
measure: Phase 2: Intracranial ORR in RET-fusion Positive NSCLC Central Nervous System (CNS) Metastases Participants
timeFrame: Up to approximately 79.8 months
measure: Phase 2: Intracranial CBR in RET-fusion Positive NSCLC CNS Metastases Participants
timeFrame: Up to approximately 79.8 months
measure: Phase 2: Intracranial DCR in RET-fusion Positive NSCLC CNS Metastases Participants
timeFrame: Up to approximately 79.8 months
measure: Phase 2: Intracranial DOR in RET-fusion Positive NSCLC CNS Metastases Participants
timeFrame: Up to approximately 79.8 months
measure: Phase 1: Maximum Plasma Concentration (Cmax)
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 1: Time to Maximum Plasma Concentration (Tmax)
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 1: Time of Last Quantifiable Plasma Drug Concentration (Tlast)
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC0-24)
timeFrame: 24 hours postdose on Day 1 of Cycle 1 (1 cycle = 28 days)
measure: Phase 1: Plasma Drug Concentration at 24 Hours Postdose (C24hr)
timeFrame: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 1: Apparent Volume of Distribution (Vz/F)
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 1: Terminal Elimination Half-Life (t½)
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 1: Apparent Oral Clearance (CL/F)
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 1: Accumulation Ratio for Cmax (RCmax)
timeFrame: 24 hours postdose on Day 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 1: Accumulation Ratio for AUC (RAUC)
timeFrame: 24 hours postdose on Day 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 2: Cmax
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 2: Tmax
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 2: Tlast
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 2: AUC0-24
timeFrame: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 2: C24hr
timeFrame: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 2: t½
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 2: CL/F
timeFrame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
measure: Phase 1: Percent Change From Baseline in Dual Specificity Phosphatase 6 (DUSP6)
timeFrame: Baseline, Week 4
measure: Phase 1: Percent Change From Baseline in Sprout Receptor Tyrosine Kinase Signaling Antagonist 4 (SPRY4)
timeFrame: Baseline, Week 4
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic-Jacksonville
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital.
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College-New York Presbyterian Hospital
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Chengdu
country: China
facility: The affiliated Cancer Hospital, School of Medicine, UESTC
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
city: Fuzhou City
country: China
facility: Fujian Provincial Cancer Hospital
city: Ganzhou
country: China
facility: First Affiliated Hospital of Gannan Medical University
city: Guangzhou
country: China
facility: Sun Yet-sen University Cancer Center
city: Guangzhou
country: China
facility: Guangdong General Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Jinan City
country: China
facility: Jinan Central Hospital
city: Lanzhou
country: China
facility: Gansu Cancer Hospital
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Tianjing
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lille
country: France
facility: Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Rennes cedex 09
country: France
facility: CHU de Rennes - Hopital de Pontchaillo
city: Toulouse
country: France
facility: Hôpital Larrey
city: Villejuif CEDEX
country: France
facility: Gustave Roussy
city: Berlin
country: Germany
facility: Helios Klinikum Emil von Behring GmbH
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: München
country: Germany
facility: Klinikum der Universität München
city: Oldenburg
country: Germany
facility: Pius-Hospital
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Ravenna
country: Italy
facility: Ospedale Santa Maria Delle Croci
state: Emilia-Romagna
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
state: Lazio
city: Milano
country: Italy
facility: IEO
state: Lombardia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda
state: Lombardia
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Hospitalet de Llobregat
country: Spain
facility: Institut Catala d Oncologia Hospitalet
state: Barcelona
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.