A Phase 1 Open-label, Multicenter, Dose Escalation Study of the Safety, Tolerability, and PK of HPN217 in Patients With R/R MM

A Phase 1 Open-label, Multicenter, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of HPN217 in Patients With Relapsed/Refractory Multiple Myeloma

An open-label, Phase 1 study of HPN217 to assess the safety, tolerability and PK in patients with relapsed/ refractory multiple myeloma

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma; Multiple Myeloma in Relapse; Multiple Myeloma With Failed Remission; Multiple Myeloma of Bone
• Intervention / Treatment: Drug: HPN217

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Harpoon Therapeutics; Phone Number: (650) 452-7280; Email: hpn217_3001ctgov@harpoontx.com

Study Locations

• France
  • Lille, France, 59000
    • The Centre Hospitalier Universitaire de Lille
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire de Nantes
  • Poitiers, France, 86021
    • Centre Hospitalier Universitaire de Poitiers
• Spain
  • Barcelona, Spain, 08916
    • Josep Carreras Leukaemia Research Institute
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz (UAM-FJD)
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Kansas
    • Fairway, Kansas, United States, 66205
      • The University of Kansas Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester James P Wilmot Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington - Seattle Cancer Center Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Major Inclusion Criteria:

1. Patients ≥18 years of age at the time of signing informed consent
2. Documented RRMM for which no standard therapy options are anticipated to result in a durable remission. Relapse defined as progressive disease after initial response (minimal response [MR] or better) to previous treatment, more than 60 days after cessation of last treatment. Refractory disease defined as <25% reduction in M protein or progression of disease during treatment or within 60 days after cessation of treatment.
3. Received at least 3 prior therapies (including proteasome inhibitor, immune modulatory drug, and an anti-CD38 antibody; patients should not be a candidate for or be intolerant of all established therapies known to provide clinical benefit in multiple myeloma).

4. Measurable disease defined as at least one of the following:

   1. Serum M-protein ≥0.5 g/dL
   2. Urine M-protein ≥200 mg/24 hours
   3. Serum free light chain (FLC) assay: Involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
5. Resolved acute effects of any prior therapy to baseline severity or Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade ≤1.

Major Exclusion Criteria:

1. Plasma cell leukemia; non-secretory myeloma (e.g., solitary plasmacytoma)
2. Patients with only extramedullary relapse of multiple myeloma who do not meet requirement for measurable disease.
3. Prior autologous peripheral stem cell transplant or prior autologous bone marrow transplantation within <90 days of the start of study
4. Prior allogeneic stem cell transplantation or solid organ transplantation within 12 months of Screening. However, any patient receiving immunosuppressive medication will be excluded.
5. History of or known or suspected autoimmune disease (exception(s): patients with vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at Screening are allowed). Other exceptions may be allowed following discussion with the Sponsor Medical Monitor for patients who have not received any treatment for their autoimmune disorder in the past 3 years
6. Second primary malignancy that has not been in remission for greater than 3 years. Exceptions that do not require a 3-year remission: non-melanoma skin cancer, resected melanoma in situ, in situ cervical cancer, adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years, low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10 ng/mL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HPN217 monotherapy dose escalation; HPN217 is IV administered once weekly for about 1 hour. Doses will vary between cohorts as MTD and/or RP2D[s] is being determined.	Drug: HPN217; HPN217 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains
Experimental: HPN217 dose escalation with extended dosing intervals; HPN217 is IV administered either once bi-weekly or weekly for the first cycle followed by a bi-weekly schedule for about 1 hour. Doses will vary between cohorts as MTD and/or RP2D[s] is being determined.	Drug: HPN217; HPN217 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency and severity of treatment-emergent AEs (TEAEs) graded according to NCI CTCAE version 5.0 (ASTCT grading criteria for CRS and ICANS)	4 years
Number and severity of DLTs following treatment with HPN217	4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of response (DOR)	4 years
Best Overall Response (BOR)	4 years
Overall response rate (ORR) based on current IMWG response criteria	4 years
Progression-free survival (PFS) and overall survival (OS)	4 years
Time to response (TTR)	4 years
Incidence of ADAs against HPN217	4 years
Titers of ADAs against HPN217	4 years
Minimal Residual Disease (MRD) negative	4 years

Collaborators and Investigators

• Sponsor: Harpoon Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Estimated): January 2, 2024
• Study Completion (Estimated): June 2, 2024

Study Registration Dates

• First Submitted: November 27, 2019
• First Submitted That Met QC Criteria: November 29, 2019
• First Posted (Actual): December 3, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 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; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: HPN217-3001

Drug and device information, study documents

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