A Phase 1 Study of BHV-1530 in Advanced Solid Tumors

Inclusion Criteria

• •1. Signed, written Independent Ethics Committee (IEC)/Institutional Review Board (IRB)-approved informed consent
• •2. Age greater than or equal to 18 years
• •3. Participants consent to provide tumor tissue collected prior to study treatment, preferably from a biopsy performed after their last anticancer therapy and within 90 days of the start of study treatment. An older archival sample may be acceptable with Sponsor approval.
• •4. Participants must have progressed following, are intolerant of, or have no available standard-of-care therapy.
• •5. Patients with histologically or cytologically confirmed locally advanced/metastatic relapsed or refractory solid tumors as outlined below:
• •* Dose-escalation and Dose-expansion (Backfill) Cohorts:
• •* Participants with urothelial cancer of the urinary tract: (including renal pelvis, ureters, urinary bladder, and urethra), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) regardless of the presence of an activating FGFR3 alteration (mutation, fusion, or amplification) or high FGFR3 protein or mRNA expression in the absence of a detectable genetic alteration.
• •* Other advanced or metastatic solid tumors with a documented activating FGFR3 alteration (mutation, fusion, or amplification) or high FGFR3 protein or mRNA expression in the absence of a detectable genetic alteration.
• •* Dose Confirmation Cohort:
• •* Participants with urothelial cancer of the urinary tract: (including renal pelvis, ureters, urinary bladder, and urethra), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) regardless of the presence of an activating FGFR3 alteration (mutation, fusion, or amplification) or high FGFR3 protein or mRNA expression in the absence of a detectable genetic alteration.
• •* Other advanced or metastatic solid tumors with a documented activating FGFR3 alteration (mutation, fusion, or amplification) or high FGFR3 protein or mRNA expression in the absence of a detectable genetic alteration, as determined by a validated assay performed in a CLIA certified local or central laboratory.
• •6. Measurable advanced or metastatic tumors per RECIST 1.1 criteria
• •7. Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• •8. Acceptable liver function:
• •* Bilirubin ≤ 1.5 × upper limit of normal (ULN). Participants with known Gilbert's syndrome who have total bilirubin level ≤3×ULN may be enrolled.
• •* AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN (if liver metastases are present, then ≤ 5 × ULN is allowed)
• •9. Acceptable renal function:
• •• Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min as calculated using the modified Cockcroft-Gault equation; confirmation of creatinine clearance is only required when creatinine is \>1.5 × ULN; 24-hour urine collection is allowed, but not required
• •10. Acceptable hematologic status:
• •* Blood transfusion or growth factor support is not allowed within 7 days prior to blood samples that will be used to establish eligibility
• •* Absolute neutrophil count greater than or equal to 1500/mm3. Participants with known Duffy null phenotype who have absolute neutrophil count ≥ 1,200/mm3 may be enrolled
• •* Platelet count greater than or equal to 100,000 mm3
• •* Hemoglobin greater than or equal to 9 g/dL
• •* Activated partial thromboplastin time (aPTT) ≤1.5×ULN. Study participants on therapeutic doses of anticoagulation medication must have INR and/or aPTT ≤ the upper limit of the therapeutic range for intended use
• •11. A negative urine or serum pregnancy test (if a woman of childbearing potential);
• •12. Women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for 7 months (for women) or 4 months (for men) after the last dose of study drug.