A Phase 1 Study of BHV-1530 (AMB302) in Advanced Solid Tumors

Eligibility 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. Life expectancy of at least 3 months;
• 4. Patients with histologically or cytologically confirmed locally advanced/metastatic relapsed or refractory solid tumors as outlined below:
• * Dose-escalation and Dose-expansion (Backfill) Cohorts:
• * Any patient for which FGFR3 is potentially important to the biology of the disease1, and who has progressed following or is intolerant of standard-of-care therapy or for which no standard therapy is available;
• * Confirmation of FGFR3 positivity (FGFR3 mutation, rearrangement, amplification and overexpression) is not required prior to enrollment on the study
• * Patients must submit an evaluable archival tissue sample to evaluate tumor for FGFR3 status
• * Dose Confirmation Cohort:
• * Any patient for which FGFR3 is important to the biology of the disease, and disease OR a patient with a cancer type in which a signal of potential efficacy was identified in dose escalation and dose expansion (as clarified in a protocol amendment), AND
• * who has progressed following or is intolerant of standard-of-care therapy or for which no standard therapy is available; AND
• * FGFR3 Status:
• * Locally- or centrally-determined, or documented overexpression or alterations of FGFR3
• 5. Measurable advanced or metastatic tumors per RECIST 1.1 criteria;
• 6. Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• 7. Acceptable liver function:
• * Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• * AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN (if liver metastases are present, then ≤ 5 × ULN is allowed)
• * Serum albumin \> 3.0 g/dL
• * Gamma-glutamyl transferase ≤ 2.5 × ULN
• 8. Acceptable renal function:
• 9. Acceptable hematologic status:
• * Absolute neutrophil count greater than or equal to 1500 cells/mm3
• * Platelet count greater than or equal to 100,000 plt/mm3
• * Hemoglobin greater than or equal to 9 g/dL
• * International normalized ratio (INR) \< 1.5 (or ≤ 3 if on warfarin or other medications for therapeutic anticoagulation)
• 10. A negative urine or serum pregnancy test (if a woman of childbearing potential);
• 11. 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. Should a female trial subject or a female partner of a male trial subject become pregnant or suspect she is pregnant during the study, the Investigator must be informed immediately.
• 1. Prior treatment with antibody drug conjugate (ADC) with a topoisomerase-I inhibitor payload. Prior direct treatment with topoisomerase inhibitor (e.g., irinotecan, topotecan, belotecan, nano-liposomal irinotecan) are not exclusionary.
• 2. Congestive heart failure according to New York Heart Association Class III or IV; moderate, severe, or clinically significant valvulopathy; myocardial infarction within the past 3 months; clinically unstable angina pectoris; or clinically significant arrhythmia requiring treatment. Patients with medically controlled atrial fibrillation are not excluded.
• 3. Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of \> 470 msec;
• 4. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy;
• 5. Primary central nervous system (CNS) or known active brain metastases;
• 6. Pregnant or nursing women;
• 7. Treatment with radiation therapy, major surgery, chemotherapy, or investigational therapy within 28 days prior to planned enrollment (6 weeks for nitrosoureas or mitomycin C). Radiation for palliation of symptoms or for bone lesions with impending risk of pathologic fracture, is allowed within 1 week prior to planned enrollment, but the lesion should not be selected as a target lesion for RECIST analysis.
• 8. Any serious toxicities from prior treatment that have not returned to baseline.
• 9. Any clinically significant corneal or retinal abnormality that may increase the risk of eye toxicity;
• 10. Known active infection with human immunodeficiency virus (HIV), human T-cell leukemia virus, type 1 (HTLV-1), hepatitis B virus (HBV), or hepatitis C virus (HCV), if allowed by local regulations:
• * Patients with a history of hepatitis B or C are allowed if HBV DNA or HCV RNA are undetectable
• * Active infection with HIV and CD4+ T-cell count \< 350/μL. Patients not on established anti-retroviral therapy for at least 4 weeks and having a detectable HIV viral load
• 11. Have a second primary malignancy that, in the judgement of the Investigator and Medical Monitor, may affect the interpretation of the results. Curatively treated in-situ cancers and non-melanomatous skin cancers are allowed.
• 12. Serious uncontrolled nonmalignant disease (e.g., renal failure, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor;
• 13. Unwillingness or inability to comply with procedures required in this protocol;
• 14. Known sensitivity to BHV-1530 or any of the excipients in BHV-1530;
• 15. History of (noninfectious) clinically significant interstitial lung disease (ILD)/pneumonitis that required steroids, active clinically significant ILD/pneumonitis, or suspected clinically significant ILD/pneumonitis that cannot be ruled out by imaging at screening.