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

NCT06384807 | Recruiting Phase 1 FDA Drug

• 1 other identifier: BHV1510-101 (PBI-410-101)
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 17

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.

Conditions

Solid Tumor

Keywords

Trop2 targeting ADC; Antibody-drug conjugate; Trop2; ADC

Outcome Measures

Primary Outcomes (5)

• Phase 1: Number of patients with adverse events (AEs)

  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.

  Through study completion, estimated as an average of 47 months

• Phase 1: Recommended doses or schedules for expansion (RDEs) and maximum tolerated dose (MTD)

  Based on tolerability and preliminary antitumor activity. This applies to both the BHV-1510 monotherapy arm and BHV-1510 in combination with Cemiplimab arm.

  Approximately 15 months

• Phase 2: Objective Response Rate (ORR) for BHV-1510 for monotherapy and in combination with cemiplimab

  Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1.

  Through study completion, estimated as an average of 47 months

• Phase 2: Number of patients with AEs for BHV-1510 for monotherapy and in combination with cemiplimab

  Incidence and severity of AEs, SAEs and DLTs. Severity of AEs will be assessed according to the NCI CTCAE v5.0

  Through study completion, estimated as an average of 47 months

• Phase 2: Duration of Response (DoR) for BHV-1510 for monotherapy and in combination with cemiplimab

  Assessed by RECIST v 1.1

  Through study completion, estimated as an average of 47 months

Secondary Outcomes (16)

• 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 Cycle 1

• 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

Study Arms (2)

BHV-1510 Monotherapy Dose Escalation

EXPERIMENTAL

Drug: BHV-1510

BHV-1510 in combination with Cemiplimab dose escalation

EXPERIMENTAL

Drug: BHV-1510; Drug: Cemiplimab

Interventions

BHV-1510 DRUG

BHV-1510 will be administered on Day 1 every 3 weeks

Also known as: PBI-410, GQ1010

BHV-1510 Monotherapy Dose Escalation; BHV-1510 in combination with Cemiplimab dose escalation

Cemiplimab DRUG

cemiplimab (350mg) will be administered as an IV infusion on Day 1 every 3 weeks

BHV-1510 in combination with Cemiplimab dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Biohaven Therapeutics Ltd.: lead

Study Sites (17)

Site-113

Duarte, California, 91010, United States

RECRUITING

Site-112

La Jolla, California, 92093, United States

RECRUITING

Site-111

Palo Alto, California, 94304, United States

RECRUITING

Site-114

Washington D.C., District of Columbia, 20016, United States

RECRUITING

Site-103

Miami, Florida, 33176, United States

RECRUITING

Site-105

Orlando, Florida, 32827, United States

RECRUITING

Site-115

Tampa, Florida, 33612, United States

RECRUITING

Site-110

Augusta, Georgia, 30912, United States

RECRUITING

Site-109

Detroit, Michigan, 48201, United States

RECRUITING

Site-101

St Louis, Missouri, 63108, United States

RECRUITING

Site-117

New York, New York, 10021, United States

RECRUITING

Site-116

Oklahoma City, Oklahoma, 73117, United States

RECRUITING

Site-108

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Site-107

Nashville, Tennessee, 37203, United States

RECRUITING

Site-104

Dallas, Texas, 75231, United States

RECRUITING

Site-106

West Valley City, Utah, 84119, United States

RECRUITING

Site-102

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Interventions

cemiplimab

Study Officials

• Chief Medical Officer

  Biohaven Pharmaceuticals, Inc.

  STUDY DIRECTOR

Central Study Contacts

Chief Medical Officer

CONTACT

203-404-0410; clinicaltrials@biohavenpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation followed by enrollment in signal-finding cohorts.

Study Record Dates

• First Submitted: April 22, 2024
• First Posted: April 25, 2024
• Study Start: April 22, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)