Study Summary
This trial is testing a new drug, pralsetinib, to see if it is safe and effective in treating medullary thyroid cancer, RET-altered non-small cell lung cancer, and other RET-altered solid tumors.
Eligible Conditions
- Lung Cancer
- Cancer
- Tumors
- Head and Neck Cancers
- Adenocarcinoma
- Digestive System Tumors
- Germ Cell Tumors
- Neurofibromatosis
- Gastrointestinal Tumors
- Intestinal Diseases
- Colonic Diseases
- Colorectal Cancer
- Papillary Thyroid Cancer
- Intestinal Tumors
- Neuroendocrine Tumors
- Endocrine Disorders
- Gastrointestinal Disorders
- Bronchial Tumors
- Glandular and Epithelial Neoplasms
- Papillary Adenocarcinoma
- Medullary Thyroid Cancer
- Endocrine Tumors
- Non-Small-Cell Lung Carcinoma
- Gastrointestinal Disease
- Non-Small Cell Lung Cancer (NSCLC)
- Thyroid Neoplasms
- Respiratory Diseases
- Neuroectodermal Tumors
- Lung Disease
- RET-altered Solid Tumors
- Neuroendocrine Carcinoma
- Thyroid Disease
Treatment Effectiveness
Effectiveness Progress
Study Objectives
8 Primary · 30 Secondary · Reporting Duration: Approximately every 8 weeks or 16 weeks based on the treatment cycle (Up to approximately 84 months)
Week 2
(Phases 1 and 2) Pharmacodynamic Parameters Including Changes in Blood Calcitonin
Carcinoembryonic Antigen
(Phases 1 and 2) Pharmacodynamic parameters including changes in blood calcitonin
(Phases 1 and 2) Pharmacodynamic parameters including tumor marker, carcinoembryonic antigen (CEA)
Week 2
(Phases 1 and 2) Pharmacokinetic Parameters Including Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC0-24)
(Phases 1 and 2) Pharmacokinetic Parameters Including Maximum Plasma Drug Concentration (Cmax)
(Phases 1 and 2) Pharmacokinetic Parameters Including Terminal Elimination Half-life (t1/2)
(Phases 1 and 2) Pharmacokinetic parameters including area under the plasma concentration versus time curve from time 0 to 24 hours postdose (AUC0-24)
(Phases 1 and 2) Pharmacokinetic parameters including maximum plasma drug concentration (Cmax)
(Phases 1 and 2) Pharmacokinetic parameters including terminal elimination half-life (t1/2)
Month 12
(Phase 1) ORR
Year 2
(Phase 1) Overall response rate
Week 16
(Phase 1) RET gene status and correlation between RET gene status and ORR, CBR, DOR, DCR, PFS and other antineoplastic measures
(Phase 2 ) Clinical Benefit Rate (CBR)
(Phase 2 ) Disease Control Rate (DCR)
(Phase 2 ) Duration of Response (DOR)
(Phase 2 ) Overall Survival (OS)
(Phase 2 ) Progression Free Survival (PFS)
(Phase 2) Assess Intracranial Response Rate and Time to Intracranial Progression in Participants With NSCLC
(Phase 2) Assess intracranial response rate and time to intracranial progression in patients with NSCLC
(Phase 2) CBR
(Phase 2) DCR
(Phase 2) DOR
(Phase 2) Overall Response Rate (ORR)
(Phase 2) Overall response rate
(Phase 2) RET gene status and correlation between RET gene status and ORR, CBR, DOR, DCR and other antineoplastic measures
Month 12
(Phase 1) RET Gene Status and Correlation Between RET Gene Status and ORR, CBR, DOR, DCR, PFS and Other Antineoplastic Measures
Month 84
(Phase 2) Overall Survival (OS)
(Phase 2) PFS
Month 12
(Phase 1) Determination of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib
Month 12
(Phase 1) Determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of pralsetinib
Day 15
(Phase 2) Electrocardiogram (ECG) Assessment Using QT Analysis
(Phase 2) Electrocardiogram (ECG) Assessment using QT analysis
Month 12
(Phase 1) Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Month 24
(Phase 2) Number of Participants with AEs and SAEs
Month 24
(Phase 1) Number of patients with adverse events and serious adverse events
(Phase 2) Number of patients with adverse events and serious adverse events
Day 28
(Phase 2) RET Gene Status and Correlation Between RET Gene Status and ORR, CBR, DOR, DCR and Other Antineoplastic Measures
Trial Safety
Safety Progress
Trial Design
2 Treatment Groups
Phase 1 Dose Escalation
1 of 2
Phase 2 Dose Expansion
1 of 2
Experimental Treatment
589 Total Participants · 2 Treatment Groups
Primary Treatment: pralsetinib (BLU-667) · No Placebo Group · Phase 1 & 2
Phase 1 Dose Escalation
Drug
Experimental Group · 1 Intervention: pralsetinib (BLU-667) · Intervention Types: DrugPhase 2 Dose Expansion
Drug
Experimental Group · 1 Intervention: pralsetinib (BLU-667) · Intervention Types: DrugTrial Logistics
Trial Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: approximately every 8 weeks or 16 weeks based on the treatment cycle (up to approximately 84 months)
Who is running the clinical trial?
Hoffmann-La RocheLead Sponsor
2,362 Previous Clinical Trials
1,067,557 Total Patients Enrolled
Clinical TrialsStudy DirectorHoffmann-La Roche
2,149 Previous Clinical Trials
875,647 Total Patients Enrolled
Eligibility Criteria
Age 18+ · All Participants · 10 Total Inclusion Criteria
Mark “Yes” if the following statements are true for you:You 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.
You 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.
You have a pathologically documented, definitively diagnosed non-resectable advanced solid tumor.
Participants must have a solid tumor per local assessment of tumor tissue and/or blood.
You have a solid tumor, as determined by local or central testing of tumor or circulating tumor nucleic acid in blood.
You have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion previously treated with a platinum-based chemotherapy.
You have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion, and you have previously received standard of care (SOC) appropriate for your tumor type.
You 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.
References
- Gainor, Justin F, Giuseppe Curigliano, Dong-Wan Kim, Dae Ho Lee, Benjamin Besse, Christina S Baik, Robert C Doebele, et al.. 2021. “Pralsetinib for RET Fusion-positive Non-small-cell Lung Cancer (ARROW): A Multi-cohort, Open-label, Phase 1/2 Study”. The Lancet Oncology. Elsevier BV. doi:10.1016/s1470-2045(21)00247-3.
- Subbiah, Vivek, Mimi I Hu, Lori J Wirth, Martin Schuler, Aaron S Mansfield, Giuseppe Curigliano, Marcia S Brose, et al.. 2021. “Pralsetinib for Patients with Advanced or Metastatic Ret-altered Thyroid Cancer (ARROW): A Multi-cohort, Open-label, Registrational, Phase 1/2 Study”. The Lancet Diabetes & Endocrinology. Elsevier BV. doi:10.1016/s2213-8587(21)00120-0.
- Popat, Sanjay, Stephen V. Liu, Nicolas Scheuer, Grace G. Hsu, Alexandre Lockhart, Sreeram V. Ramagopalan, Frank Griesinger, and Vivek Subbiah. 2022. “Addressing Challenges with Real-world Synthetic Control Arms to Demonstrate the Comparative Effectiveness of Pralsetinib in Non-small Cell Lung Cancer”. Nature Communications. Springer Science and Business Media LLC. doi:10.1038/s41467-022-30908-1.
- Subbiah, Vivek, Philippe A. Cassier, Salvatore Siena, Elena Garralda, Luis Paz-Ares, Pilar Garrido, Ernest Nadal, et al.. 2022. “Pan-cancer Efficacy of Pralsetinib in Patients with RET Fusion–positive Solid Tumors from the Phase 1/2 ARROW Trial”. Nature Medicine. Springer Science and Business Media LLC. doi:10.1038/s41591-022-01931-y.
- 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. Erratum In: Lancet Diabetes Endocrinol. 2021 Oct;9(10):e4.
- 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. Erratum In: Lancet Oncol. 2021 Aug;22(8):e347.
- 2017. "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". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03037385.
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