A Phase 1/2 Study of BHV-1510 (Previously PBI-410) in Advanced Solid Tumors

This is a Phase 1/2, first in human (FIH), open-label, multicenter study of BHV-1510, a Trop-2 directed antibody-drug conjugate (ADC), in participants with previously treated, advanced solid tumors. The study comprises 2 parts: a Phase 1 Dose Escalation and a Phase 2 Dose Expansion. The Phase 1 will investigate the safety and tolerability of BHV-1510 given in monotherapy and given in combination with cemiplimab and identify one or more recommended doses for expansion (RDEs) and the maximum-tolerated dose (MTD) (if one exists). Once the RDE has been established, Phase 2 will open to investigate the preliminary efficacy of BHV-1510 in signal-finding expansion cohorts.

Key Inclusion Criteria:

• Male or female participants aged ≥18 years.
• Unresectable, incurable, locally advanced or metastatic epithelial-origin solid tumor that is refractory to standard therapies, or has no approved standard therapies, or no approved standard therapies at its current treatment stage. If applicable to the tumor type, participants must have received platinum-based chemotherapy, standard of care immunotherapy, and standard of care targeted therapies.
• Measurable disease (per RECIST 1.1).
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Participants have adequate hematologic, renal, liver, and coagulation function as defined by the following (blood transfusion or growth factor support is not allowed within 7 days prior to blood samples that will be used to establish eligibility):

• Hemoglobin ≥9 g/dL
• Absolute neutrophil count >1,500/mm3; participants with known Duffy null phenotype who have absolute neutrophil count ≥1,200/mm3 may be enrolled
• Platelets >100,000/mm3
• Creatinine clearance ≥50 mL/min measured or estimated using the Cockcroft-Gault formula; 24-hour urine collection is allowed, but not required.
• Total bilirubin ≤1.5 × upper limit of normal (ULN); participants with known Gilbert's syndrome who have total bilirubin level ≤3×ULN may be enrolled.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5×ULN (or ≤5×ULN for participants with hepatic metastases)
• Alkaline phosphatase <2.5×ULN (or ≤5×ULN for participants with hepatic and/or bone metastases)
• International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN
• 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
• Have recovered (ie, improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo.

BHV-1510 in Combination with specific inclusion criteria:

• histologically or cytologically documented advanced (locally, recurrent, inoperable, cannot betreated with curative intent) or metastatic cancer including Endometrial Carcinoma that is confirmed as proficient mismatch repair (pMMR)
• received ≤ 2 prior lines of systemic anti-cancer therapy and at most one prior anti-programmed cell death protein 1 (PD-1) (programmed death-ligand 1 [PD-L1]) therapy for advanced/ metastatic disease.

Key Exclusion Criteria:

• Women who are pregnant or lactating.
• Clinically significant intercurrent disease.
• Has symptomatic brain metastases or has had any radiation or surgery for brain metastases within 4 weeks of C1D1.
• Has clinically significant corneal disease.
• Requires supplemental oxygen for daily activities.
• Previous treatment with a Trop-2-targeted therapy, including Trop-2 ADCs.
• Has a medical history of interstitial lung disease (eg, noninfectious interstitial pneumonia requiring steroid treatment, pneumonitis, pulmonary fibrosis, or severe radiation pneumonitis) or current interstitial lung disease or are suspected to have any of these diseases based on imaging at Screening.
• Any standard cancer therapy (eg, chemotherapy, hormonal therapy, radiotherapy, immunotherapy, biologic therapy treatment) or experimental therapy within 3 weeks or 5 half-lives, whichever is shorter, prior to C1D1. The interval may be reduced to 2 weeks for bone and visceral metastasis therapy. Any major surgical procedure within 6 weeks prior to C1D1.
• History of severe hypersensitivity reactions to other monoclonal antibodies or either the drug substances or inactive ingredients of BHV-1510.
• Has current or previously treated leptomeningeal carcinomatosis.
• Use of OAP1B1 and OATP1B3 inhibitors within 14 days prior to starting trial.

BHV-1510 in Combination Specific Exclusion Criteria:

• Hypersensitivity to cemiplimab or any of its excipients or contraindicated to cemiplimab per approved local labeling.
• Experienced Grade 3 or higher immune-related AEs with prior treatment of anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Prior allogeneic stem cell or solid organ transplantation.
• Patients with history of myocarditis.
• Presence of cardiovascular disease