Clinical trial NCT06384807: A Phase 1/2 Study of BHV-1510 (Previously PBI-410) in Advanced Solid Tumors
Official title: A Phase 1/2, First in Human, Dose Escalation and Dose Expansion Study of BHV-1510 (Previously PBI-410) as Monotherapy and in Combination With Anti-Cancer Agents in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Keywords: Trop2 targeting ADC
Antibody-drug conjugate
Trop2
ADC
Lead sponsor: Biohaven Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2024-04-25
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation followed by enrollment in signal-finding cohorts.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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 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-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.

Primary outcomes:
measure: Phase 1: Number of patients with adverse events (AEs)
timeFrame: Through study completion, estimated as an average of 47 months
measure: Phase 1: Recommended dose for expansion (RDE) and maximum tolerated dose (MTD)
timeFrame: Approximately 15 months
measure: Phase 2: Objective Response Rate (ORR) for BHV-1510 for monotherapy and in combination with cemiplimab
timeFrame: Through study completion, estimated as an average of 47 months
measure: Phase 2: Number of patients with AEs for BHV-1510 for monotherapy and in combination with cemiplimab
timeFrame: Through study completion, estimated as an average of 47 months
measure: Phase 2: Duration of Response (DoR) for BHV-1510 for monotherapy and in combination with cemiplimab
timeFrame: Through study completion, estimated as an average of 47 months
Secondary outcomes:
measure: Phase 1 and 2: Maximum Plasma Concentration (Cmax) of BHV-1510, total antibody and payload (BHC-0080269)
timeFrame: Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3
measure: 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
timeFrame: Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3
measure: Phase 1 and 2: Area Under the Concentration versus time curve extrapolated to infinity (AUCinf) of BHV-1510, total antibody and payload
timeFrame: Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3
measure: Phase 1 and 2: Area under the concentration versus time curve over the dosing interval (AUCtau) of BHV-1510, total antibody and payload
timeFrame: Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3
measure: Phase 1 and 2: Elimination half-life (t1/2) of BHV-1510, total antibody and payload
timeFrame: Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3
measure: Phase 1 and 2: Trough concentration (Ctrough) of BHV-1510, total antibody and payload
timeFrame: Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3
measure: Phase 1 and 2: Total body clearance (CL) of BHV-1510 and total antibody
timeFrame: Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3
measure: Phase 1 and 2: Volume of distribution at steady state (Vss) of BHV-1510 and total antibody
timeFrame: Up to 8 timepoints, but not exceeding, 22 days in Cycles 1 and 3
measure: Phase 1: ORR
timeFrame: Through study completion, estimated as an average of 47 months
measure: Phase 1: Duration of Response (DoR)
timeFrame: Through study completion, estimated as an average of 47 months
measure: Phase 1 and 2: Immunogenicity of BHV-1510
timeFrame: Through study completion, estimated as an average of 47 months
measure: Phase 2: Disease control rate (DCR) for BHV-1510 for monotherapy and in combination with cemiplimab
timeFrame: Through study completion, estimated as an average of 47 months
measure: Phase 2: Progression free survival (PFS) for BHV-1510 for monotherapy and in combination with cemiplimab
timeFrame: Through study completion, estimated as an average of 47 months
measure: Phase 2: Overall survival (OS) for BHV-1510 for monotherapy and in combination with cemiplimab
timeFrame: Through study completion, estimated as an average of 47 months
measure: 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)
timeFrame: Approximately 15 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Site-113
state: California
city: La Jolla
country: United States
facility: Site-112
state: California
city: Palo Alto
country: United States
facility: Site-111
state: California
city: Washington
country: United States
facility: Site-114
state: District of Columbia
city: Miami
country: United States
facility: Site-103
state: Florida
city: Orlando
country: United States
facility: Site-105
state: Florida
city: Augusta
country: United States
facility: Site-110
state: Georgia
city: Detroit
country: United States
facility: Site-109
state: Michigan
city: Saint Louis
country: United States
facility: Site-101
state: Missouri
city: Philadelphia
country: United States
facility: Site-108
state: Pennsylvania
city: Nashville
country: United States
facility: Site-107
state: Tennessee
city: Dallas
country: United States
facility: Site-104
state: Texas
city: West Valley City
country: United States
facility: Site-106
state: Utah
city: Fairfax
country: United States
facility: Site-102
state: Virginia
Study officials:
affiliation: Biohaven Pharmaceuticals, Inc.
name: Chief Medical Officer
role: STUDY_DIRECTOR
References: