Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial 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.
Phase
Phase 1/Phase 2
Funding Agency/Sponsor
Industrial
Disease
Thoracic Oncology
Enrollment Eligibility
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