Study to Assess Safety of HDP-101 in Patients With Relapsed Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This study will assess the safety, tolerability, pharmacokinetics (PK) and the therapeutic potential of HDP-101 in patients with plasma cell disorders including multiple myeloma.

Detailed Description
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The study will consists of two parts: a Part 1 dose escalation phase and a Part 2a expansion phase for safety, tolerability, PK, PD, and clinical activity testing. The study will enroll subjects with relapsed/refractory MM or other plasma cell disorders expressing BCMA. An adaptive 2-parameter Bayesian logistic regression model (BLRM) for dose-escalation with overdose control will be used in the dose-escalation phase for determination of the MTD or the RP2D. Dose-expansion phase of the study aims to collect preliminary evidence of antitumor activity and to confirm the safety of the HDP-101 as a monotherapy.

Official Title
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A Phase 1/2a, First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of HDP-101 in Patients With Plasma Cell Disorders Including Multiple Myeloma

Conditions
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Multiple Myeloma, Plasma Cell Disorder

Intervention / Treatment
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* Drug: HDP-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥18 years. Life expectancy >12 weeks. Eastern Cooperative Oncology Group Performance Status (PS) of 0 to 2. A confirmed diagnosis of active MM according to the diagnostic criteria established by the International Myeloma Working Group (IMWG). Must have undergone SCT or is considered transplant ineligible. Must have undergone prior treatments with antimyeloma therapy which must have included an immunomodulatory drug, proteasome inhibitor, and anti-CD38 treatment, alone or in combination. In addition, the patient should either refractory or intolerant to any established standard of care therapy providing a meaningful clinical benefit for the patient assessed by the Investigator. Measurable disease as per IMWG criteria. Adequate organ system function as defined in protocol. Exclusion Criteria: For patient entering the Phase 2a part only: Prior treatment with any approved or experimental BCMA-targeting modalities are not allowed. Known central nervous system involvement. Plasma cell leukemia. History of congestive heart failure. Autologous or allogenic SCT within 12 weeks before the first infusion or is planning for autologous SCT. Symptomatic graft versus host disease post allogenic hemopoietic cell transplant within 12 months prior to the first study treatment infusion. Radiotherapy within 21 days prior to the first study treatment infusion. History of any other malignancy known to be active. Known human immunodeficiency virus infection. Patients with active infection requiring systemic anti-infective. Patients with positive test results for hepatitis B surface antigen or Hepatitis B core antigen. Patients with positive test results for hepatitis C virus (HCV) infection. Current active liver or biliary disease.

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
Intervention Model: Single Group Assignment
Interventional Model Description: Eligible patients will be enrolled and treated with intravenous HDP-101 every 3 weeks. A Bayesian logistic regression model will be used to guide dose-escalation during Phase 1 and select the best dose for the Phase 2a of the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HDP-101<br>Participants will receive HDP-101 intravenously at one dose every 3 weeks (21 day cycle) until disease progression, intolerable toxicity, Investigator's discretion or patient withdrawal. During the phase 1 tolerability of different dose levels will be evaluated. During the phase 2a dose expansion part the recommended phase 2 dose (RP2D) of HDP-101 will be administered. | Drug: HDP-101<br>* HDP-101 is available as lyophilized white powder for preparation of infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who experience dose-limiting toxicity (DLT) during the first cycle of treatment - Part 1 as defined in Clinical Study Protocol |  | Up to Day 21 (from first dose) | 
| Objective response rate (ORR) | Proportion of enrolled subjects who achieve a partial response (PR) or better, i.e. stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and PR, according to the IMWG criteria. | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and tolerability of HDP-101 | Number of patients with serious and non-serious adverse events grouped by system organ class and preferred terms based on Common Terminology Criteria for Adverse Events (CTCAE v 5.0) classification. | Through study completion, an average of 1 year | 
| To assess the anticancer activity of HDP-101 in terms of time-to-event (TTE) | Clinical efficacy of HDP-101 measured by Progression Free Survival (PFS) and Overall Survival (OS). | Through study completion, an average of 1 year |