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
- Conditions
- Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid TumorsLung Cancer and Other Advanced Solid TumorsThyroid Cancer10038667
- Registration Number
- NL-OMON56358
- Lead Sponsor
- F. Hoffmann La-Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 23
1. Patient is >= 18 years of age.
2. 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 MTC, or a
RET-altered solid tumor per local assessment of tumor tissue and/or
blood.
• Phase 1 enrichment patients must have MTC or a RET-altered solid
tumor per local assessment of tumor tissue and/or blood.
3. Diagnosis during dose expansion (Phase 2) - All patients (with the
exception of patients with MTC enrolled in Groups 3 and 4) must have an
oncogenic RET fusion or
mutation (excluding synonymous, frameshift, and nonsense mutations)
solid tumor, as determined by local 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 - 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 cabozantinib 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 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, previously treated with a selective TKI that inhibits RET, such
as LOXO-292.
• 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.
4. Patients must have non-resectable disease. Prior to protocol amendment 9,
patients
must have progressed following standard therapy or have not
adequately responded to standard therapy, or the patient 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.
5. Dose expansion (Phase 2) patients in all groups (except group 7) must
have measurable disease per RECIST v1.1 (or RANO, if appropriate for
tumor type).
6. Patient agrees to provide tumor tissue (archived, if available or a fre
1. Patient's cancer has a known primary driver alteration other than RET.
Investigators should discuss enrollment with Sponsor regarding comutations
2. Patient has any of the following within 14 d prior to the first dose of
IMP:
a. Platelet count < 75 × 109/L
b. Absolute neutrophil count < 1.0 × 109/L
c. 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 1st IMP dose
d. AST or ALT > 3 × ULN if no hepatic metastases are present; > 5 × ULN
if hepatic metastases are present
e. Total bilirubin > 1.5 × ULN; > 3 × ULN with direct bilirubin > 1.5 ×
ULN in presence of Gilbert's disease
f. Estimated (Cockroft-Gault formula) or measured creatinine clearance
< 40 mL/min
g. Total serum phosphorous > 5.5 mg/dL
3. Patient has a QTcF > 470 msec. Patient has a history of prolonged QT
syndrome or Torsades de pointes. Patient has a familial history of
prolonged QT syndrome
4. Patient has clinically significant, uncontrolled, cardiovascular disease
including congestive heart failure Grade III or IV according to the New
York Heart Association classification; myocardial infarction or unstable
angina within the previous 6 months, uncontrolled hypertension, or
clinically significant, uncontrolled arrhythmias, including
bradyarrhythmias that may cause QT prolongation
5. Patient has CNS metastases or a primary CNS tumor associated with
progressive neurological symptoms or requires increasing doses of
corticosteroids to control the CNS disease. If a patient requires
corticosteroids for management of CNS disease, the dose must have
been stable for the 2 weeks preceding C1D1
6. Presence of clinically symptomatic interstitial lung disease or
interstitial pneumonitis, including radiation pneumonitis
7. Patient received the following anti-cancer therapy:
a. Any systemic anticancer therapy (except for immunotherapy or other
antibody therapies) and all forms of radiotherapy within 14 d or 5 halflives
prior to first IMP dose. IMP may be started within these washout
periods if considered by the Investigator to be safe and within the best
interest of the patient prior Sponsor approval
b. Any immunotherapy or other antibody therapy within 28 d prior to the
1st dose of IMP (immune related toxicities must have resolved to <
Grade 2 prior to starting IMP)
8. Dose expansion patients in Groups 1-5 and 7 (Phase 2): patient has
previously received treatment with a selective RET inhibitor such as
selpercatinib
9. Patient received neutrophil growth factor support within 14 d of 1st
IMP dose
10. Patient requires treatment with a prohibited medication or herbal remedy
that cannot be discontinued at least 2 weeks before start of IMP
administration. IMP may be started within 14 d or 5 half-lives of prior
therapy if considered by the Investigator to be safe and within the best
interest of the patient, with prior Sponsor approval
11. Patient has had a major surgical procedure within 14 d of the first
IMP dose
12. Patient has a history of another primary malignancy that has been
diagnosed or required therapy (except maintenance anti-hormonal
therapy) within the past year. The following prior malignancies are not
Not exclusionary are: completely resected basal cell and squamous cell
skin cancer, curativel
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase 2, Dose Expansion Objectives<br /><br>Primary Objectives<br /><br>• To determine the overall response rate (ORR) by Response Evaluation Criteria<br /><br>in Solid Tumors (RECIST) v1.1 (or Response Assessment in Neuro-Oncology [RANO],<br /><br>if appropriate for tumor type) according to patients* disease type, and/or<br /><br>RET-altered status if applicable, and/or prior treatment status if appropriate.<br /><br>• To further define the safety and tolerability of pralsetinib</p><br>
- Secondary Outcome Measures
Name Time Method