Advanced solid tumor
Conditions
Interventions
dose escalation group:BLU-667
dose expansion group:BLU-667
Sponsors
None listed
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Patient is >= 18 years of age. 2. Diagnosis during dose escalation (Part 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. Part 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 (Part 2) – All patients (with the exception of Groups 3, 4 and 9) must have an oncogenic RET 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. For a list of common oncogenic mutation, see Appendix 6. 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. 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 previously treated with SOC appropriate for the tumor type and 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. 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. Group 9: patients must have pathologically documented, definitively diagnosed advanced MTC that has progressed within 14 months prior to the Screening Visit and was previously treatment nave. 4. Patient must have non-resectable disease 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 (Part 2) patients in groups 1, 2, 3, 4, 6, 8, and 9 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 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 Part 2, Group 6, patients ar
Exclusion criteria
Exclusion criteria: 1. Patients 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. Investigators should discuss enrollment with Sponsor regarding co-mutations. 2. Patient has any of the following within 14 days prior to the first dose of study drug: a. Platelet count 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 (NYHA) 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 (eg, Type II second degree heart block or third degree heart block). 5. Patient has central nervous system (CNS) metastases or a primary CNS tumor that is 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 (ie, affecting activities of daily living or requiring therapeutic intervention). 7. Patient received anticancer therapy (including both systemic therapy and radiotherapy, but not including immunotherapy or other antibody therapies) within 14 days or 5 half-lives prior to the first dose of study drug. Patients who received previous immunotherapy or other antibody therapy, within 28 days (immune related toxicities must have resolved to < Grade 2 prior to starting BLU-667). BLU-667 may be started within these washout periods if considered by the Investigator to be safe and within the best interest of the patient, with prior Sponsor approval. 8. Dose expansion patients in Groups 1-5 and 7-9 (Part 2): patient has previously received treatment with a selective RET inhibitor such as LOXO-292. 9. Patient received neutrophil growth factor support within 14 days of the first dose of study drug. 10. Patient requires treatment with a prohibited medication or herbal remedy (as specified in Appendix 2) that cannot be discontinued at least 2 weeks before the start of study drug administration. BLU-667 may be started within 14 days 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 days of the first dose of study drug (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures). 12. Patient has a history of another primary malignancy that has been diagnosed or required therapy within the past year. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, curatively tr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR by tumor type and by each expansion group;Overall safety profile of BLU-667, as assessed by the type, frequency, severity, timing, and relationship to study drug of any AEs, SAEs, changes in vital signs, ECGs, and safety laboratory tests.; | — |
Countries
China
Contacts
Public ContactKe Wang
West China Hospital, Sichuan University
Outcome results
None listed