A Phase 1 Study of BHV-1530 in Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Solid Tumor
• Interventions: Drug: BHV-1530

• Registration Number: NCT06874335
• Lead Sponsor: Biohaven Therapeutics Ltd.

Brief Summary

This is a Phase 1, first in human (FIH), open-label, multicenter study of BHV-1530 in adult participants with advanced or metastatic solid tumors.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-04
• Study First Submitted QC: 2025-03-07
• Study First Posted: 2025-03-13
• Study Start: 2025-03-20
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-09
• Last Update Posted: 2025-05-14
• Primary Completion: 2029-03
• Study Completion: 2029-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 95

Inclusion Criteria

1. Signed, written Independent Ethics Committee (IEC)/Institutional Review Board (IRB)-approved informed consent

2. Age greater than or equal to 18 years

3. Patients with histologically or cytologically confirmed locally advanced/metastatic relapsed or refractory solid tumors as outlined below:

   • Dose-escalation and Dose-expansion (Backfill) Cohorts:

     • Any patient for which FGFR3 is potentially important to the biology of the disease, and who has progressed following or is intolerant of standard-of-care therapy or for which no standard therapy is available
     • Confirmation of FGFR3 positivity (FGFR3 mutation, rearrangement, amplification and overexpression) is not required prior to enrollment on the study
     • Patient consent to provide tumor tissue collected prior to study treatment, preferably from a biopsy performed after their last anticancer therapy and within 90 days of the start of study treatment. An older archival sample may be acceptable with Sponsor approval

   • Dose Confirmation Cohort:

     • Any patient for which FGFR3 is important to the biology of the disease, and disease OR a patient with a cancer type in which a signal of potential efficacy was identified in dose escalation and dose expansion (as clarified in a protocol amendment), AND
     • who has progressed following or is intolerant of standard-of-care therapy or for which no standard therapy is available; AND
     • FGFR3 Status:
     • Locally- or centrally-determined, or documented overexpression or alterations of FGFR3

4. Measurable advanced or metastatic tumors per RECIST 1.1 criteria

5. Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

6. Acceptable liver function:

   • Bilirubin ≤ 1.5 × upper limit of normal (ULN). Participants with known Gilbert's syndrome who have total bilirubin level ≤3×ULN may be enrolled.
   • AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN (if liver metastases are present, then ≤ 5 × ULN is allowed)

7. Acceptable renal function:

   • Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min as calculated using the modified Cockcroft-Gault equation; confirmation of creatinine clearance is only required when creatinine is >1.5 × ULN; 24-hour urine collection is allowed, but not required

8. Acceptable hematologic status:

   • Blood transfusion or growth factor support is not allowed within 7 days prior to blood samples that will be used to establish eligibility
   • Absolute neutrophil count greater than or equal to 1500/mm3. Participants with known Duffy null phenotype who have absolute neutrophil count ≥ 1,200/mm3 may be enrolled
   • Platelet count greater than or equal to 100,000 mm3
   • Hemoglobin greater than or equal to 9 g/dL
   • 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

9. A negative urine or serum pregnancy test (if a woman of childbearing potential);

10. Women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for 7 months (for women) or 4 months (for men) after the last dose of study drug.

Exclusion Criteria

1. Prior treatment with antibody drug conjugate (ADC) with a topoisomerase-I inhibitor payload. Prior direct treatment with topoisomerase inhibitor (e.g., irinotecan, topotecan, belotecan, nano-liposomal irinotecan) are not exclusionary.

2. Participant has clinically significant intercurrent disease including, but not limited to:

   • New York Heart Association Class III or IV heart failure
   • Myocardial infarction, unstable angina, or stroke within 3 months prior to C1D1
   • Newly diagnosed thromboembolic events that require therapeutic intervention within 6 months prior to C1D1 (participants with stable control of lower limb deep venous thrombosis over at least 3 months are allowed)
   • Severe aortic stenosis
   • Uncontrolled arrhythmia
   • Symptomatic pericardial effusion
   • Congenital long QT syndrome
   • A mean of Fredericia's formula-QT corrected interval (QTcF) prolongation to >470 msec based on a 12-lead ECG
   • Uncontrolled hypertension (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg) or diabetes (hemoglobin A1C ≥9.0%)
   • Left ventricular ejection fraction (LVEF) <45% determined by echocardiogram or multiple gated acquisition scan (MUGA)
   • Symptomatic pleural effusion (<90% oxygen saturation)

3. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy

4. Primary central nervous system (CNS) tumors, current or previously treated leptomeningeal disease or known active brain metastases.

   NOTE: Participants with previously treated, clinically stable, radiologically stable brain metastases maybe eligible

5. Pregnant or nursing women

6. Any standard cancer therapy (e.g., chemotherapy, hormonal therapy, radiotherapy, immunotherapy, biologic therapy treatment) or experimental therapy within 4 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

7. Participants have not recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo. If the participant has an ongoing, stable, chronic Grade 2 toxicity they may be eligible after discussion with Sponsor on a case-by-case basis

8. Any clinically significant corneal or retinal abnormality that may increase the risk of eye toxicity

9. Known active infection with human immunodeficiency virus (HIV), human T-cell leukemia virus, type 1 (HTLV-1), hepatitis B virus (HBV), or hepatitis C virus (HCV), if allowed by local regulations:

   • Participants with hepatitis B (hepatitis B virus surface antigen [HbsAg] positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV ribonucleic acid). Participants with HCV with undetectable virus after treatment are eligible. Participants with a prior history of hepatitis B virus are eligible if quantitative polymerase change reaction for hepatitis B virus DNA is negative
   • Participants with human immunodeficiency virus (HIV) infection with acquired immune deficiency syndrome (AIDS) defining illness are not eligible for enrollment; however, participants who have had HIV infection and who have a cluster of differentiation 4 (CD4) + T cell count >350 cells/μL and no history of an AIDS-defining illness are eligible for entry

10. Has an active second malignancy. Note: participants with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or participants with surgically cured tumors with low risk of recurrence (e.g., nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ) are allowed

11. Participants who in the opinion of the Investigator will not be able to adhere to the schedule of assessments and/or may have difficulties complying with the treatment regimen or are unwilling or unable to comply with procedures required in this protocol

12. Known sensitivity to BHV-1530 or any of the excipients in BHV-1530;

13. History of (noninfectious) clinically significant interstitial lung disease (ILD)/pneumonitis that required steroids, active clinically significant ILD/pneumonitis, or suspected clinically significant ILD/pneumonitis that cannot be ruled out by imaging at screening.

14. Requires supplemental oxygen for daily activities

15. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
BHV-1530 Monotherapy	BHV-1530	-

Primary Outcome Measures

Name	Time	Method
Dose-escalation and Dose-expansion Cohorts: Number of patients with AEs	Through study completion, estimated as an average of 48 months	Incidence and severity of treatment emergent adverse events (TEAEs), including dose-limiting toxicities (DLTs) and serious adverse events (SAEs)
Dose-confirmation Cohorts: Recommended dose of BHV-1530 for later phase trials	Through study completion, estimated as an average of 48 months	Incidence and severity of adverse events (AEs) and SAEs, dose reductions during treatment, study discontinuation rates due to TEAEs, and signals of antitumor activity

Secondary Outcome Measures

Name	Time	Method
Dose-escalation and Dose-expansion Cohorts: Time of maximum concentration (Tmax)	Through study completion, estimated as an average of 48 months	Time of maximum concentration of BHV-1530, total antibody and TopoIx BHV-0080269
Dose-escalation and Dose-expansion Cohorts: Elimination half-life (t½)	Through study completion, estimated as an average of 48 months	Terminal elimination half-life (t½) of BHV-1510, total antibody and TopoIx BHV-0080269
Dose-escalation and Dose-expansion Cohorts: Area Under the Concentration versus time curve (AUC)	Through study completion, estimated as an average of 48 months	Area under the concentration-time curve from zero to last quantifiable concentration (AUC0-t) and AUC extrapolated to infinity (AUC0-inf) and AUC over the dosing interval (AUCtau)
Dose-escalation and Dose-expansion Cohorts: Trough concentration (Ctrough)	Through study completion, estimated as an average of 48 months	Trough concentration of BHV-1530, total antibody and TopoIx BHV-0080269
Dose-escalation and Dose-expansion Cohorts: Total body clearance (CL)	Through study completion, estimated as an average of 48 months	Total body clearance of BHV-1530 and total antibody
Dose-escalation and Dose-expansion Cohorts: Volume of distribution at steady state (Vss)	Through study completion, estimated as an average of 48 months	Volume of distribution of BHV-1530 and total antibody
Dose-escalation and Dose-expansion Cohorts: Time to Response (TTR)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-escalation and Dose-expansion Cohorts: Disease Control Rate (DCR)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-escalation and Dose-expansion Cohorts: Clinical Benefit Rate (CBR)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-escalation and Dose-expansion Cohorts: Duration of Response (DOR)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-escalation and Dose-expansion Cohorts: Progression-free Survival (PFS)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-escalation and Dose-expansion Cohorts: Maximum observed serum concentration (Cmax)	Through study completion, estimated as an average of 48 months	Serum concentration of BHV-1530, total antibody and TopoIx BHV-0080269
Dose-escalation and Dose-expansion Cohorts: Objective Response Rate (ORR)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-confirmation Cohorts: Objective Response Rate (ORR)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-confirmation Cohorts: Disease Control Rate (DCR)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-confirmation Cohorts: Time to Response (TTR)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-confirmation Cohorts: Duration of Response (DOR)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-confirmation Cohorts: Progression-free Survival (PFS)	Through study completion, estimated as an average of 48 months	Assessed by RECIST v 1.1
Dose-confirmation Cohorts: Maximum observed serum concentration (Cmax)	Through study completion, estimated as an average of 48 months	Serum concentration of BHV-1530, total antibody and free payload TopoIx BHV-0080269
Dose-confirmation Cohorts: Time of maximum concentration (Tmax)	Through study completion, estimated as an average of 48 months	Time of maximum concentration of BHV-1530, total antibody and TopoIx BHV-0080269
Dose-confirmation Cohorts: Elimination half-life (t½) of BHV-1530	Through study completion, estimated as an average of 48 months	Terminal elimination half-life (t½) of BHV-1510, total antibody and TopoIx BHV-0080269
Dose-confirmation Cohorts: Area Under the Concentration versus time curve (AUC)	Through study completion, estimated as an average of 48 months	Area under the concentration-time curve from zero to last quantifiable concentration (AUC0-t) and AUC extrapolated to infinity (AUC0-inf) and AUC over the dosing interval (AUCtau)
Dose-confirmation Cohorts: Trough concentration (Ctrough)	Through study completion, estimated as an average of 48 months	Trough concentration of BHV-1530, total antibody and TopoIx BHV-0080269
Dose-confirmation Cohorts: Total body clearance (CL)	Through study completion, estimated as an average of 48 months	Total body clearance of BHV-1530 and total antibody
Dose-confirmation Cohorts: Volume of distribution at steady state (Vss)	Through study completion, estimated as an average of 48 months	Volume of distribution of BHV-1530 and total antibody

Trial Locations

Locations (4)

Site-103; 🇺🇸 Austin, Texas, United States

Site-105; 🇺🇸 San Antonio, Texas, United States

Site-102; 🇺🇸 Fairfax, Virginia, United States

Site-101; 🇺🇸 Irving, Texas, United States