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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Plasma Cell Disorder
• Intervention / Treatment: Drug: HDP-101

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.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: András Strassz, MD; Phone Number: + 49 6203 1009 0; Email: clinical@hdpharma.com

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Not yet recruiting
    • Charité - Campus Benjamin Franklin Med. Klinik m.S. Hämatologie, Onkologie
  • Chemnitz, Germany, 09116
    • Not yet recruiting
    • Klinikum Chemnitz gGmbH, Klinik f. Innere Medizin III
  • Hamburg, Germany, 22763
    • Not yet recruiting
    • Asklepios Klinik Altona, Haematologie und internistische Onkologie
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitätsklinikum Heidelberg
  • Kiel, Germany, 24105
    • Recruiting
    • Universitätsklinikum Schleswig-Holstein
  • Köln, Germany, 50937
    • Not yet recruiting
    • Universitätsklinikum Köln
  • Lübeck, Germany, 23538
    • Not yet recruiting
    • UKSH Campus Lübeck Klinik für Hämatologie und Onkologie
  • Mainz, Germany, 55131
    • Recruiting
    • Universitätsklinikum Mainz
• Hungary
  • Budapest, Hungary, 1083
    • Not yet recruiting
    • Semmelweis University, Belgyogyaszati es Onkologiai Klinika
  • Budapest, Hungary, 1122
    • Recruiting
    • National Institute of Oncology, Department of Oncological Internal Medicine
• Poland
  • Katowice, Poland, 40-519
    • Recruiting
    • Pratia Onkologia Katowice
  • Opole, Poland, 45-061
    • Not yet recruiting
    • Szpital Wojewódzki w Opolu
  • Łódź, Poland, 93-513
    • Not yet recruiting
    • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute of Emory University
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai, The Tisch Cancer Instutute
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HDP-101; 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; HDP-101 is available as lyophilized white powder for preparation of infusion.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Heidelberg Pharma AG

Publications and helpful links

General Publications

• Strassz A, Raab MS, Orlowski RZ, Kulke M, Schiedner G, Pahl A. A First in Human Study Planned to Evaluate HDP-101, an Anti-BCMA Amanitin Antibody-Drug Conjugate with a New Payload and a New Mode of Action, in Multiple Myeloma. Blood 2020; 136 (Supplement 1): 34. doi: https://doi.org/10.1182/blood-2020-142285

Helpful Links

• Oral presentation - ASH Congress 2020

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: April 23, 2021
• First Submitted That Met QC Criteria: May 4, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Paraproteinemias
• Other Study ID Numbers: HDP-101-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No