Clinical Trial 23420

• Overview

  Study 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

  Summary:

  his 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.

  Objective:

  Primary: * To assess the initial safety and tolerability of BHV-1510 as monotherapy and to identify one or more recommended doses for expansion (RDEs) and the maximum-tolerated dose (MTD) (if one exists). Secondary: * To assess the pharmacokinetic (PK) profile of BHV-1510 (antibody-drug conjugate [ADC]), total antibody, and payload (H0011). * To assess the preliminary efficacy of BHV-1510 * To assess the incidence of antidrug antibody (ADA) against BHV-1510.

• Treatments

  Therapies:

  Antibody-Drug Conjugate; Immunotherapy

  Medications:

  BHV-1510 (); Cemiplimab (); REGN2810 (Cemiplimab)

• Inclusion 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 in protocol (blood transfusion or growth factor support is not allowed within 7 days prior to blood samples that will be used to establish eligibility).
  • 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.
  • Participants assigned to receive BHV-1510 SC must, in the treating physician’s best clinical judgement, be able to receive subcutaneous administrations into the anterior abdominal wall.
  • Other criteria may apply

• Exclusion Criteria

  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 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.
  • Presence of cardiovascular disease.
  • Other criteria may apply

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