A Phase 1/2 Open-label, Multicenter, Dose Escalation and Dose ExpansionStudy of the Safety, Tolerability, and Pharmacokinetics of HPN217 in Patientswith Relapsed/Refractory Multiple Myeloma

Recruitment & Eligibility

Status: Pending

Sex: All

Target Recruitment: 70

Inclusion Criteria

Major Inclusion Criteria:

Received at least 3 prior therapies (including proteasome inhibitor, immune modulatory drug, and an anti-CD38 antibody; patients should not be a candidate for or be intolerant of all established therapies known to provide clinical benefit in multiple myeloma).
Measurable disease defined as at least one of the following:

Serum M-protein =0.5 g/dL
Urine M-protein =200 mg/24 hours
Serum free light chain (FLC) assay: Involved FLC level =10 mg/dL (=100 mg/L)
Eastern Cooperative Oncology Group (ECOG) performance status =2.
Adequate hematologic status, including:

Absolute neutrophil count (ANC) =1000 cells/µL
Platelet count =50,000/µL (without transfusions)
Hemoglobin =8 g/dL
Adequate renal function, including:

a. Calculated creatinine clearance =30 mL/min using the formula of Cockcroft and Gault

Adequate hepatic function, including

Total bilirubin =1.5 × upper limit of normal (ULN), regardless of direct bilirubin
AST and ALT =3.0 × ULN (=5.0× ULN if due to myeloma involvement)
Alkaline phosphatase =3× ULN (=5.0× ULN if due to myeloma involvement)

Exclusion Criteria

Major Exclusion Criteria:

Prior exposure to BCMA-targeting agents (Part 2 only)
Concurrent treatment with anti-tumor necrosis factor alpha therapies, systemic corticosteroids (prednisone dose >10 mg per day or equivalent), or other immune suppressive drugs within the 2 weeks prior to Screening

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary Endpoints:<br>• Frequency and severity of treatment-emergent AEs (TEAEs) graded according to NCI CTCAE<br>version 5.0.<br>• Change from baseline in clinical laboratory parameters, vital signs, and ECGs.<br>• Number and severity of DLTs following treatment with HPN217.<br>• PK parameters of HPN217:<br>o Single dose - maximum concentration (Cmax), time to maximum concentration (Tmax),<br>area under the single dose concentration-time curve over dosing interval t (AUCsd, t),<br>area under the concentration-time curve extrapolated to infinity (AUCinf), terminal<br>elimination half-life (t1/2), and clearance (CL) as data permit<br>o Multiple dose (assuming steady state is achieved) - maximum concentration (Css,max),<br>time to maximum concentration (Tss,max), area under the steady state<br>concentration-time curve over dosing interval t (AUCss, t), t1/2, minimum concentration<br>(Css,min), CL, volume of distribution (Vss), and accumulation ratio (AUCss,t/AUCsd, t) as<br>data permit

Secondary Outcome Measures

Name	Time	Method
Secondary Endpoints:<br>• Overall response rate (ORR) based on IMWG response criteria<br>• Progression-free survival (PFS) and overall survival (OS)<br>• Duration of response (DOR)<br>• Incidence and titers of ADAs against HPN217

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