A Phase 1, Multicenter, Open-Label, Dose Escalation, Dose Expansion and Dose Confirmation Study of BHV-1530 in Adult Participants with Advanced or Metastatic Solid Tumors

Cancer Categories

Brain and Nervous System,Gastrointestinal (GI),Genitourinary (GU),Head and Neck

Karmanos Trial ID

2025-038

NCT ID

NCT06874335

Age Group

Adult

Scope

National

Phase

Phase I

Principal Investigator

Anthony
Shields, M.D., Ph.D.
Oncology - Medical View Profile

Objective:

Primary Objective:

Dose-escalation and Dose-expansion Cohorts

To determine the safety profile, maximum tolerable dose (MTD), minimally reproducible active dose (MRAD), and recommended dose range (RDR) of BHV-1530 administered by IV infusion dosed Q3W.

Dose-confirmation Cohorts

To determine the recommended dose (RD) of BHV-1530 for later phase trials.

Secondary Objectives:

Dose-escalation and Dose-expansion Cohorts

To assess the preliminary efficacy of BHV-1530
To determine the PK of BHV-1530, total antibody, and free payload TopoIx (BHC-0080269)
To assess the incidence of antidrug antibody (ADA) against BHV-1530

Dose-confirmation Cohort

To assess the preliminary efficacy of BHV-1530
To determine the PK of BHV-1530, total antibody, and free payload TopoIx BHC-0080269
To assess the incidence of ADA against BHV-1530

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Eligibility

Inclusion Criteria:

Signed, written Independent Ethics Committee (IEC)/Institutional Review Board (IRB)-approved informed consent
Age greater than or equal to 18 years
Participants 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.
Participants must have progressed following, are intolerant of, or have no available standard-of-care therapy.
Patients with histologically or cytologically confirmed locally advanced/metastatic relapsed or refractory solid tumors as outlined below:

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

Participants with urothelial cancer of the urinary tract: (including renal pelvis, ureters, urinary bladder, and urethra), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) regardless of the presence of an activating FGFR3 alteration (mutation, fusion, or amplification) or high FGFR3 protein or mRNA expression in the absence of a detectable genetic alteration.
Other advanced or metastatic solid tumors with a documented activating FGFR3 alteration (mutation, fusion, or amplification) or high FGFR3 protein or mRNA expression in the absence of a detectable genetic alteration.

Dose Confirmation Cohort:

Participants with urothelial cancer of the urinary tract: (including renal pelvis, ureters, urinary bladder, and urethra), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) regardless of the presence of an activating FGFR3 alteration (mutation, fusion, or amplification) or high FGFR3 protein or mRNA expression in the absence of a detectable genetic alteration.
Other advanced or metastatic solid tumors with a documented activating FGFR3 alteration (mutation, fusion, or amplification) or high FGFR3 protein or mRNA expression in the absence of a detectable genetic alteration, as determined by a validated assay performed in a CLIA certified local or central laboratory.

Measurable advanced or metastatic tumors per RECIST 1.1 criteria
Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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)

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

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

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

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.
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 ≤ 6 months prior to C1D1
Newly diagnosed thromboembolic events that require therapeutic intervention over the last 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)

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

Pregnant or nursing women
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
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
Any clinically significant corneal or retinal abnormality that may increase the risk of eye toxicity
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

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 tumors cured with radiotherapy or surgery with low risk of recurrence (e.g., non melanoma skin cancer, histologically confirmed complete excision of carcinoma in situ) are allowed
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
Known sensitivity to BHV-1530 or any of the excipients in BHV-1530;
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.
Requires supplemental oxygen for daily activities

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 1-800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 1-800-527-6266

Applicable Disease Site

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