A Phase 1 Open-label, Multicenter, Dose Escalation Study of the Safety, Tolerability, and PK of HPN217 in Patients With R/R MM

Study Overview
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Brief Summary
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An open-label, Phase 1 study of HPN217 to assess the safety, tolerability and PK in patients with relapsed/ refractory multiple myeloma

Official Title
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A Phase 1 Open-label, Multicenter, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of HPN217 in Patients With Relapsed/Refractory Multiple Myeloma

Conditions
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Multiple Myeloma in Relapse, Multiple Myeloma, Multiple Myeloma of Bone, Multiple Myeloma With Failed Remission

Intervention / Treatment
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* Drug: HPN217


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Patients ≥18 years of age at the time of signing informed consent Documented RRMM for which no standard therapy options are anticipated to result in a durable remission. Relapse defined as progressive disease after initial response (minimal response [MR] or better) to previous treatment, more than 60 days after cessation of last treatment. Refractory disease defined as <25% reduction in M protein or progression of disease during treatment or within 60 days after cessation of treatment. 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) and an abnormal serum FLC ratio (<0.26 or >1.65) Resolved acute effects of any prior therapy to baseline severity or Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade ≤1. Major Exclusion Criteria: Plasma cell leukemia; non-secretory myeloma (e.g., solitary plasmacytoma) Patients with only extramedullary relapse of multiple myeloma who do not meet requirement for measurable disease. Prior autologous peripheral stem cell transplant or prior autologous bone marrow transplantation within <90 days of the start of study Prior allogeneic stem cell transplantation or solid organ transplantation within 12 months of Screening. However, any patient receiving immunosuppressive medication will be excluded. History of or known or suspected autoimmune disease (exception(s): patients with vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at Screening are allowed). Other exceptions may be allowed following discussion with the Sponsor Medical Monitor for patients who have not received any treatment for their autoimmune disorder in the past 3 years Second primary malignancy that has not been in remission for greater than 3 years. Exceptions that do not require a 3-year remission: non-melanoma skin cancer, resected melanoma in situ, in situ cervical cancer, adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years, low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10 ng/mL

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPN217 monotherapy dose escalation<br>HPN217 is IV administered once weekly for about 1 hour. Doses will vary between cohorts as MTD and/or RP2D[s] is being determined. | Drug: HPN217<br>* HPN217 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains<br>|
| Experimental: HPN217 dose escalation with extended dosing intervals<br>HPN217 is IV administered either once bi-weekly or weekly for the first cycle followed by a bi-weekly schedule for about 1 hour. Doses will vary between cohorts as MTD and/or RP2D[s] is being determined. | Drug: HPN217<br>* HPN217 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of treatment-emergent AEs (TEAEs) graded according to NCI CTCAE version 5.0 (ASTCT grading criteria for CRS and ICANS) |  | 4 years | 
| Number and severity of DLTs following treatment with HPN217 |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) |  | 4 years | 
| Overall response rate (ORR) based on current IMWG response criteria |  | 4 years | 
| Progression-free survival (PFS) and overall survival (OS) |  | 4 years | 
| Duration of response (DOR) |  | 4 years | 
| Time to response (TTR) |  | 4 years | 
| Incidence of ADAs against HPN217 |  | 4 years | 
| Titers of ADAs against HPN217 |  | 4 years | 
| Minimal Residual Disease (MRD) negative |  | 4 years |