A Phase 1/2 Study of BHV-1510 (Previously PBI-410) in Advanced Solid Tumors
- Registration Number
- NCT06384807
- Lead Sponsor
- Biohaven Therapeutics Ltd.
- Brief Summary
This is a Phase 1/2, first in human (FIH), open-label, multicenter study of BHV-1510 monotherapy and in Combination with Cemiplimab in participants with previously treated, advanced solid tumors.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 280
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Male or female participants aged ≥18 years.
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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.
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Measurable disease (per RECIST 1.1).
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Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
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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
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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 be treated with curative intent) or metastatic cancer.
- 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
- 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-only radiation 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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description BHV-1510 Monotherapy Dose Escalation BHV-1510 - BHV-1510 in combination with Cemiplimab dose escalation BHV-1510 - BHV-1510 in combination with Cemiplimab dose escalation Cemiplimab -
- Primary Outcome Measures
Name Time Method Phase 1: Number of patients with adverse events (AEs) Through study completion, estimated as an average of 47 months Description: Incidence and severity of AEs, serious adverse events (SAEs) and dose limiting toxicities (DLTs). Severity of AEs will be assessed according to the NCI CTCAE v5.0. This applies to both the BHV-1510 monotherapy arm and BHV-1510 in combination with Cemiplimab arm.
Phase 1: Recommended dose for expansion (RDE) and maximum tolerated dose (MTD) Approximately 15 months Based on tolerability and preliminary antitumor activity. This applies to both the BHV-1510 monotherapy arm and BHV-1510 in combination with Cemiplimab arm.
Phase 2: Objective Response Rate (ORR) for BHV-1510 for monotherapy and in combination with cemiplimab Through study completion, estimated as an average of 47 months Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1.
Phase 2: Number of patients with AEs for BHV-1510 for monotherapy and in combination with cemiplimab Through study completion, estimated as an average of 47 months Incidence and severity of AEs, SAEs and DLTs. Severity of AEs will be assessed according to the NCI CTCAE v5.0
Phase 2: Duration of Response (DoR) for BHV-1510 for monotherapy and in combination with cemiplimab Through study completion, estimated as an average of 47 months Assessed by RECIST v 1.1
- Secondary Outcome Measures
Name Time Method Phase 2: Overall survival (OS) for BHV-1510 for monotherapy and in combination with cemiplimab Through study completion, estimated as an average of 47 months OS is defined as the time period from the start of administration to death due to any cause
Phase 2: Effects of BHV-1510 monotherapy and payload on the QTc interval using the Fridericia's correction method (QTcF), and on other ECG parameters (heart rate [HR], PR, and QRS interval) Approximately 15 months Phase 1 and 2: Maximum Plasma Concentration (Cmax) of BHV-1510, total antibody and payload (BHC-0080269) Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3 Phase 1 and 2: Area Under the Concentration versus time Curve from the end of infusion to the last measurable concentration (AUClast) of BHV-1510, total antibody and payload Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3 Phase 1 and 2: Area Under the Concentration versus time curve extrapolated to infinity (AUCinf) of BHV-1510, total antibody and payload Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3 Phase 1 and 2: Area under the concentration versus time curve over the dosing interval (AUCtau) of BHV-1510, total antibody and payload Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3 Phase 1 and 2: Elimination half-life (t1/2) of BHV-1510, total antibody and payload Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3 Phase 1 and 2: Trough concentration (Ctrough) of BHV-1510, total antibody and payload Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3 Phase 1 and 2: Total body clearance (CL) of BHV-1510 and total antibody Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3 Phase 1 and 2: Volume of distribution at steady state (Vss) of BHV-1510 and total antibody Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3 Phase 1: ORR Through study completion, estimated as an average of 47 months Assessed by RECIST v 1.1. This applies to both the BHV-1510 monotherapy arm and BHV-1510 in combination with Cemiplimab arm.
Phase 1: Duration of Response (DoR) Through study completion, estimated as an average of 47 months Assessed by RECIST v 1.1. This applies to both the BHV-1510 monotherapy arm and BHV-1510 in combination with Cemiplimab arm.
Phase 1 and 2: Immunogenicity of BHV-1510 Through study completion, estimated as an average of 47 months Incidence of ADA at baseline and post-treatment, including ADA titer
Phase 2: Disease control rate (DCR) for BHV-1510 for monotherapy and in combination with cemiplimab Through study completion, estimated as an average of 47 months Assessed by RECIST v 1.1
Phase 2: Progression free survival (PFS) for BHV-1510 for monotherapy and in combination with cemiplimab Through study completion, estimated as an average of 47 months Assessed by RECIST v 1.1
Trial Locations
- Locations (12)
City of Hope
🇺🇸Duarte, California, United States
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
Miami Cancer institute/Baptist Health South Florida
🇺🇸Miami, Florida, United States
Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Washington University School of Med
🇺🇸Saint Louis, Missouri, United States
SCRI Thomas Jefferson
🇺🇸Philadelphia, Pennsylvania, United States
SCRI TN Oncology
🇺🇸Nashville, Tennessee, United States
SCRI Lake Nona: Florida Cancer Specialists
🇺🇸Orlando, Florida, United States
NEXT Dallas
🇺🇸Dallas, Texas, United States
START Mountain Region
🇺🇸West Valley City, Utah, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States