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

  • STATUS
    Recruiting
  • End date
    Feb 29, 2024
  • participants needed
    647
  • sponsor
    Hoffmann-La Roche
Updated on 9 July 2021
cancer
metastatic disease
cytotoxic drug
systemic therapy
lung cancer
nucleic acid
cytotoxic chemotherapy
metastasis
cabozantinib
pralsetinib
mitomycin c
RET
chemotherapy regimen
vandetanib
primary cancer
cancer chemotherapy
antineoplastic agents
antineoplastic
solid tumour
solid tumor
advanced solid tumor
solid neoplasm
metastatic cancer
platinum-based chemotherapy
immunomodulator
metastatic nsclc
advanced malignant solid tumor
stage iv nsclc
immunostimulants
medullary thyroid carcinoma
ret inhibitor
blu-667
medullary thyroid cancer
stage iv non-small cell lung cancer
mg++
lung carcinoma
metastatic non-small cell lung cancer

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 patients with medullary thyroid cancer, RET-altered NSCLC and other RET-altered solid tumors.

Description

The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase 2). Both parts will enroll patients 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 patients 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.

Details
Condition Colonic Diseases, Gastrointestinal Neoplasm, Bronchogenic Carcinoma, Non-Small Cell Lung Cancer, Endocrine disorder, Endocrine neoplasm, Neuroendocrine Tumor, Pulmonary Disease, Intestinal Cancer, Intestinal Diseases, Adenocarcinoma, Papillary adenocarcinoma, Neuroectodermal Tumor, Colorectal Cancer, Rectal disorder, Neuroendocrine carcinoma, Thyroid Adenoma, Cancer, Respiratory Tract Diseases, Respiratory Tract Neoplasm, Thoracic Neoplasms, Carcinoma, Malignant neoplasm of colon, Lung Neoplasm, GASTROINTESTINAL DISORDER, Neoplasm of unspecified nature of digestive system, Digestive System Disease, Bronchial Neoplasm, head and neck cancer, Neoplasms, Nerve Tissue, Thyroid disorder, Epithelioma, Germ cell tumor, Neoplasms by Histologic Type, Neoplasms by Site, Vulvar Dysplasia and Carcinoma, Colon Cancer Screening, Cancer/Tumors, Gastrointestinal Diseases and Disorders, Rectal Disorders, Colon cancer; rectal cancer, Solid Tumor, Papillary Thyroid Cancer, Ewing's Family Tumors, Medullary Thyroid Cancer, Advanced Malignancies, Medullary Thyroid Carcinoma, Papillary Thyroid Carcinoma, Thyroid Papillary Carcinoma, Cancer (Pediatric), Neurectoderma, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Lung Cancer, Colon Cancer, Thyroid Disease, Malignant Adenoma, Lung Disease, Neoplasms, Thyroid Disorders, Germ Cell Tumors, Thyroid Cancer, Bowel Dysfunction, Digestive System Neoplasms, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Thyroid Cancer, Papillary, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Thyroid Cancer, Papillary, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Thyroid Cancer, Papillary, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Thyroid Cancer, Papillary, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Thyroid Cancer, Papillary, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Thyroid Cancer, Papillary, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Thyroid Cancer, Papillary, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Thyroid Cancer, Papillary, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Thyroid Cancer, Papillary, colorectal neoplasm, digestive system neoplasm, head and neck neoplasms, thyroid neoplasm, colonic neoplasm, head and neck tumor, colonic disease, gastrointestinal diseases, gastrointestinal disorders, gastrointestinal disease, pulmonary diseases, lung diseases, pulmonary disorders, pact, adenocarcinomas, gastrointestinal tumor, gastrointestinal tract tumor, gastrointestinal tumors, digestive system tumor, cancer, colorectal, colorectal tumor, tumors, colorectal, digestive disorders, digestive diseases, digestive disorder, digestive disease, lung tumor, respiratory tract disease, carcinomas, bowel disorders, enteropathy, bowel disease, intestinal disease, diseases of the intestinal tract, endocrinopathy, endocrine disorders, endocrine disease, endocrine diseases, endocrine neoplasia, intestinal tumors, neuroendocrine tumors, neuroendocrine tumour, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, RET-altered Non Small Cell Lung Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors
Treatment BLU-667, pralsetinib (BLU-667)
Clinical Study IdentifierNCT03037385
SponsorHoffmann-La Roche
Last Modified on9 July 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Diagnosis during dose escalation (Phase 1) - Pathologically documented, definitively diagnosed non-resectable advanced solid tumor
All patients treated at doses > 120 mg per day must have medullary thyroid cancer (MTC), or a RET-altered solid tumor per local assessment of tumor tissue and/or blood
Diagnosis during dose expansion (Phase 2) - All patients (with the exception of patients 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 - patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion previously treated with a platinum-based chemotherapy
Group 2 - patients 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 - patients must have pathologically documented, definitively diagnosed advanced MTC that has progressed within 14 months prior to the Screening Visit and was previously treated with cabozantinib and/or vandetanib
Group 4 - patient must have pathologically documented, definitively diagnosed advanced MTC that has progressed within 14 months prior to the Screening Visit and was not previously treat with cabozantinib and/or vandetanib
Group 5 -patients must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion, have previously received 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 be eligible for any of the other groups
Group 6 - patients must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion or mutation that was previously treated with a selective TKI that inhibits RET
Group 7 - patients 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 - patients 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 - patients must have pathologically documented, definitively diagnosed advanced MTC that has 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)
Patients must have non-resectable disease
Patient 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, patients are required to undergo a pretreatment biopsy to define baseline RET status in tumor tissue
Patient has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1

Exclusion Criteria

Patient'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
Patient has 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
Patients in Groups 1-5 and 7 (Phase 2) previously treated with a selective RET inhibitor
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