Clinical trial NCT04879043: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Plasma Cell Disorder
Lead sponsor: Heidelberg Pharma AG
Sponsor class: INDUSTRY
First posted: 2021-05-10
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of patients who experience dose-limiting toxicity (DLT) during the first cycle of treatment - Part 1 as defined in Clinical Study Protocol
timeFrame: Up to Day 21 (from first dose)
measure: Objective response rate (ORR)
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Assess the safety and tolerability of HDP-101
timeFrame: Through study completion, an average of 1 year
measure: To assess the anticancer activity of HDP-101 in terms of time-to-event (TTE)
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: New York
country: United States
facility: Mount Sinai, The Tisch Cancer Instutute
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Berlin
country: Germany
facility: Charité - Campus Benjamin Franklin Med. Klinik m.S. Hämatologie, Onkologie
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH, Klinik f. Innere Medizin III
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona, Haematologie und internistische Onkologie
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Lübeck
country: Germany
facility: UKSH Campus Lübeck Klinik für Hämatologie und Onkologie
city: Mainz
country: Germany
facility: Universitätsklinikum Mainz
city: Budapest
country: Hungary
facility: Semmelweis University, Belgyogyaszati es Onkologiai Klinika
city: Budapest
country: Hungary
facility: National Institute of Oncology, Department of Oncological Internal Medicine
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Opole
country: Poland
facility: Szpital Wojewodzki w Opolu
city: Łódź
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
Study officials:
References:
citation: 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