A Phase 1/2 Study of PBI-410 in Advanced Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase 1/2, First in Human, Dose Escalation and Dose Expansion Study of PBI-410 in Participants With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06384807
• Other study ID #: BHV1510-101 (PBI-410-101)
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 22, 2024
• Est. completion date: February 2028

Study information

• Verified date: June 2024
• Source: Biohaven Pharmaceuticals, Inc.
• Contact: Chief Medical Officer
• Phone: 203-404-0410
• Email: clinicaltrials[@]biohavenpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/2, first in human (FIH), open-label, multicenter study of PBI-410 in participants with previously treated, advanced solid tumors.

Description:

This is a Phase 1/2, first in human (FIH), open-label, multicenter study of PBI-410, 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 PBI-410 and identify one or more recommended doses for expansion (RDEs) and the maximum-tolerated dose (MTD) (if one exists). Phase 2 will investigate the preliminary efficacy of PBI-410 in signal-finding expansion cohorts.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: February 2028
• Est. primary completion date: February 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• 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.

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 PBI-410.

• 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 most recent imaging.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• PBI-410
PBI-410 will be administered as an IV infusion on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
United States	NEXT Dallas	Dallas	Texas
United States	NEXT Virginia	Fairfax	Virginia
United States	Miami Baptist	Miami	Florida
United States	SCRI Lake Nona: Florida Cancer Specialists	Orlando	Florida
United States	START Mountain Region	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Biohaven Therapeutics Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Through study completion, estimated as an average of 47 months
Primary	Phase 1: Recommended dose for expansion (RDE) and maximum tolerated dose (MTD)	Based on tolerability and preliminary antitumor activity	Approximately 15 months
Primary	Phase 2: Objective Response Rate (ORR)	Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1	Through study completion, estimated as an average of 47 months
Primary	Phase 2: Number of patients with AEs	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
Primary	Phase 2: Duration of Response (DoR)	Assessed by RECIST v 1.1	Through study completion, estimated as an average of 47 months
Secondary	Phase 1 and 2: Maximum Plasma Concentration (Cmax) of PBI-410		Up to, but not exceeding, 22 days
Secondary	Phase 1 and 2: Area Under the Concentration versus time Curve (AUClast) from the end of infusion to the last measurable concentration of PBI-410		Up to, but not exceeding, 22 days
Secondary	Phase 1 and 2: Area Under the Concentration versus time curve extrapolated to infinity (AUCinf)		Up to, but not exceeding, 22 days
Secondary	Phase 1 and 2: Elimination half-life (t1/2) of PBI-410 in plasma		Up to, but not exceeding, 22 days
Secondary	Phase 1: ORR	Assessed by RECIST v 1.1	Through study completion, estimated as an average of 47 months
Secondary	Phase 1: Duration of Response (DoR)	Assessed by RECIST v 1.1	Through study completion, estimated as an average of 47 months
Secondary	Phase 1 and 2: Immunogenicity of PBI-410	Incidence of ADA at baseline and post-treatment, including ADA titer	Through study completion, estimated as an average of 47 months
Secondary	Phase 2: Disease control rate (DCR)	Assessed by RECIST v 1.1	Through study completion, estimated as an average of 47 months
Secondary	Phase 2: Progression free survival (PFS)	Assessed by RECIST v 1.1	Through study completion, estimated as an average of 47 months
Secondary	Phase 2: Overall survival (OS)	OS is defined as the time period from the start of administration to death due to any cause	Through study completion, estimated as an average of 47 months