Trial Title:
A Phase 1/2 Study of BHV-1510 (Previously PBI-410) in Advanced Solid Tumors
NCT ID:
NCT06384807
Condition:
Solid Tumor
Conditions: Official terms:
Neoplasms
Cemiplimab
Conditions: Keywords:
Trop2 targeting ADC
Antibody-drug conjugate
Trop2
ADC
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Dose escalation followed by enrollment in signal-finding cohorts.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PBI-410
Description:
PBI-410 will be administered as an IV infusion on Day 1 of each 21-day cycle.
Arm group label:
PBI-400 Monotherapy Dose Escalation
Arm group label:
PBI-410 in combination with Cemiplimab dose escalation
Other name:
BHV1510
Other name:
GQ1010
Intervention type:
Drug
Intervention name:
Cemiplimab
Description:
cemiplimab (350mg) will be administered as an IV infusion on Day 1 of each 21-day cycle
Arm group label:
PBI-410 in combination with Cemiplimab dose escalation
Summary:
This is a Phase 1/2, first in human (FIH), open-label, multicenter study of PBI-410
monotherapy and PBI-410 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 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
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 PBI-410 in signal-finding expansion cohorts.
Criteria for 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
- 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.
PBI-410 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 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.
PBI-410 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Miami Baptist
Address:
City:
Miami
Zip:
33176
Country:
United States
Status:
Recruiting
Facility:
Name:
SCRI Lake Nona: Florida Cancer Specialists
Address:
City:
Orlando
Zip:
32827
Country:
United States
Status:
Recruiting
Facility:
Name:
NEXT Dallas
Address:
City:
Dallas
Zip:
75231
Country:
United States
Status:
Recruiting
Facility:
Name:
START Mountain Region
Address:
City:
West Valley City
Zip:
84119
Country:
United States
Status:
Recruiting
Facility:
Name:
NEXT Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Start date:
April 22, 2024
Completion date:
February 2028
Lead sponsor:
Agency:
Biohaven Therapeutics Ltd.
Agency class:
Industry
Source:
Biohaven Pharmaceuticals, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06384807
