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

Official title

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

Overview

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

• Drug HDP-101
  HDP-101 is available as lyophilized white powder for preparation of infusion.

Primary outcome measures

• Number of patients who experience dose-limiting toxicity (DLT) during the first cycle of treatment - Part 1 as defined in Clinical Study Protocol [Time frame: Up to Day 21 (from first dose)]
• Objective response rate (ORR) [Time frame: Through study completion, an average of 1 year]

Secondary outcome measures (2)

• Assess the safety and tolerability of HDP-101 [Time frame: Through study completion, an average of 1 year]
• To assess the anticancer activity of HDP-101 in terms of time-to-event (TTE) [Time frame: Through study completion, an average of 1 year]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 8 centers

• Charité - Campus Benjamin Franklin Med. Klinik m.S. Hämatologie, Onkologie — Berlin
• Klinikum Chemnitz gGmbH, Klinik f. Innere Medizin III — Chemnitz
• Universitätsklinikum Köln — Cologne
• Asklepios Klinik Altona, Haematologie und internistische Onkologie — Hamburg
• Universitätsklinikum Heidelberg — Heidelberg
• Universitätsklinikum Schleswig-Holstein — Kiel
• UKSH Campus Lübeck Klinik für Hämatologie und Onkologie — Lübeck
• Universitätsklinikum Mainz — Mainz

Poland · 6 centers

• Pratia Onkologia Katowice — Katowice
• Pratia Onkologia Kraków — Krakow
• Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodz — Lodz
• Szpital Wojewodzki w Opolu — Opole
• AIDPORT Sp. zo.o. — Skórzewo
• MICS Centrum Medyczne Torun — Torun

United States · 5 centers

• Winship Cancer Institute of Emory University — Atlanta
• Norton Healthcare, Inc. — Louisville
• Nebraska Cancer Institute — Omaha
• Mount Sinai, The Tisch Cancer Instutute — New York
• MD Anderson Cancer Center — Houston

Hungary · 3 centers

• Semmelweis University, Belgyogyaszati es Onkologiai Klinika — Budapest
• National Institute of Oncology, Department of Oncological Internal Medicine — Budapest
• Pécsi Tudományegyetem Klinikai Központ — Pécs

Romania · 2 centers

• Arensia Clinics SRL — Bucharest
• Oncology Institute Prof. Dr. Ion Chiricuta I.O.C.N. — Cluj-Napoca

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

Identifiers

NCT: NCT04879043 · HDP-101-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗