Multiple Myeloma, Plasma Cell Disorder
Conditions
Brief summary
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
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.
Interventions
DRUGHDP-101
HDP-101 is available as lyophilized white powder for preparation of infusion.
Sponsors
Heidelberg Pharma AG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eligible patients will be enrolled and treated with intravenous HDP-101 every 3 weeks. In Phase 1 dose-escalation part from Cohort 6 additional treatment arms are introduced for dose-optimization purposes with dosing every 3 weeks, split dosing weekly or split dosing in the first cycle on Day1 and Day8. 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Through study completion, an average of 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the safety and tolerability of HDP-101 | Through study completion, an average of 1 year | 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. |
| To assess the anticancer activity of HDP-101 in terms of time-to-event (TTE) | Through study completion, an average of 1 year | Clinical efficacy of HDP-101 measured by Progression Free Survival (PFS) and Overall Survival (OS). |
Countries
Germany, Hungary, Poland, Romania, United States
Contacts
CONTACTLei Wang, MD
Outcome results
None listed