Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN

NCT03386513 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: IMGN632-08012024-514195-40-00
• Study Type: interventional
• Target: 179
• Locations: 6 countries
• Sites: 28

Brief Summary

This is an open-label, multi-center, Phase 1/2 study to determine the MTD and assess the safety, tolerability, PK, immunogenicity, and anti-leukemia activity of IMGN632 when administered as monotherapy to patients with CD123+ disease.

Conditions

Blastic Plasmacytoid Dendritic Cell Neoplasm; Myeloproliferative Neoplasm

Keywords

Antibody Drug Conjugate; Other Hematologic Malignancies; Myeloproliferative Neoplasms; CD123; MDS; Relapsed, Refractory; Acute Lymphocytic Leukaemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• To assess the rate of composite CR in BPDCN patients

  CR+clinical CR \[CRc\]

  21-day cycle

Secondary Outcomes (11)

• To assess the duration of CR (DOCR) for patients with CR or CRc

  Up to 24 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

  Up to 24 months

• To assess the rate of CR+CRc+CRh

  Up to 24 months

• To assess the duration of CR+CRc+CRh

  Up to 24 months

• To assess ORR: CR+CRc+CRh+CRi+PR

  Up to 24 months

Study Arms (1)

Escalation and Expansion

EXPERIMENTAL

Escalation: IMGN632 was administered by IV on 2 different schedules for participants with relapsed/refractory AML, ALL, or BPDCN. Expansion: IMGN632 was administered by IV: * Cohort 1: Relapsed or refractory BPDCN participants who have received 1-3 prior systemic therapies (incl. tagraxofusp-erzs and/or any other systemic therapy deemed appropriate for the treatment of BPDCN) * Cohort 2: Relapsed AML * Cohort 3: Relapsed or refractory ALL * Cohort 4: Other relapsed or refractory hematologic malignancies * Cohort 5: Relapsed or refractory AML at alternate dose or schedule * Cohort 6: Pivotal cohort for frontline BPDCN participants who have not received prior systemic therapy and participants with frontline BPDCN who have prior or concomitant hematologic malignancy (PCHM) and have not received prior systemic therapy.

Drug: IMGN632

Interventions

IMGN632 DRUG

CD123-targeted ADC

Escalation and Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease Characteristics:
• a. Confirmation of CD123 positivity by flow cytometry or IHC. Participants who received prior CD123-targeting agents will be allowed as long as the blasts still have detectable CD123 expression.
• Cohort 1 - Participants with relapsed or refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN) with 1-3 prior lines of therapy
• Cohort 2 - Participants with relapsed AML
• Cohort 3 - Participants with relapsed relapsed or refractory ALL (including any subtypes: B-cell, T-cell, Ph+ and Ph-)
• Cohort 4 - Participants with relapsed or refractory other hematologic malignancies not included in the cohorts above (eg, high risk/very high-risk MDS, MPN, CMML, BP-CML).
• Cohort 5 - Participants with relapsed relapsed or refractory (to nonintense therapies) CD123+ AML.
• Cohort 6 - Participants with frontline de novo BPDCN at screening who have not received prior systemic therapy and participants with frontline BPDCN who have PCHM and have not received prior systemic therapy.
• Note: Participants in Cohort 6 may have received local therapy (radiotherapy, surgical excision, photodynamic therapy). Eligible participants must have a recurrence or progression in the field of local therapy OR disease outside the field of local therapy.

You may not qualify if:

• Participants who, in the judgment of their treating physician, have appropriate standard of care therapies will be excluded from Cohorts 1 through 5.
• Frontline BPDCN participants with central nervous system (CNS) disease will be excluded. A lumbar puncture must be performed during the 28-day screening period, prior to drug administration. Relapsed or refractory BPDCN participants with a known history of CNS disease must have been treated locally, have at least 1 lumbar puncture with no evidence of CNS disease, and must be clinically stable prior to first dose. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is permitted with the approval of the Sponsor.
• Participants with a history of veno-occlusive disease (sinusoidal obstruction syndrome) of the liver.
• Participants with a history of Grade 4 capillary leak syndrome, or non-cardiac Grade 4 edema are ineligible, eg, related to tagraxofusp-erzs or other etiology.
• Interval from prior cancer therapy: 1. For frontline BPDCN participants with prior local therapy (eg, radiotherapy), participants must not have received treatment within 14 days prior to drug administration on this study. 2. Relapsed or refractory BPDCN participants must not have received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational agents within 14 days prior to drug administration on this study. Participants must have recovered to baseline from all acute toxicity from this prior therapy.
• Note: the exception that participants who have received a checkpoint inhibitor must not have received that therapy within 28 days prior to drug administration on this study.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (28)

Banner Health MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Stanford

Stanford, California, 94305, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Novant Health Cancer Institute Hematology

Charlotte, North Carolina, 28204, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Novant Health Cancer Institute Hematology - Forsyth

Winston-Salem, North Carolina, 27103, United States

Location

Baylor Scott & White University Medical Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030-7095, United States

Location

Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Recherche Clinique-Hématologie

Amiens, France

Location

CHU de Besancon, Hopital Jean Minjoz

Besançon, 25030, France

Location

Institut Paoli Calmettes (Marseille)

Marseille, 13009, France

Location

Hôpital St Antoine

Paris, France

Location

CHU Bordeaux Hôpital Haut-Lévêque

Pessac, 33600, France

Location

University Hospital of Cologne

Cologne, 50937, Germany

Location

University Hospital of Leipzig

Leipzig, 04103, Germany

Location

IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola Malpighi

Bologna, 40138, Italy

Location

Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

Instituto Europeo di Oncologia

Milan, 20141, Italy

Location

Azienda ospedaliera Santa Maria della Misericordia

Perugia, 06132, Italy

Location

Hospital Universitari I Politècnic La Fe

Valencia, 46026, Spain

Location

Churchill Hospital - Oxford

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• Daver NG, Montesinos P, DeAngelo DJ, Wang ES, Papadantonakis N, Todisco E, Sweet KL, Pemmaraju N, Lane AA, Torres-Minana L, Thompson JE, Konopleva MY, Sloss CM, Watkins K, Bedse G, Du Y, Malcolm KE, Zweidler-McKay PA, Kantarjian HM. Pivekimab sunirine (IMGN632), a novel CD123-targeting antibody-drug conjugate, in relapsed or refractory acute myeloid leukaemia: a phase 1/2 study. Lancet Oncol. 2024 Mar;25(3):388-399. doi: 10.1016/S1470-2045(23)00674-5.

  PMID: 38423051 DERIVED

MeSH Terms

Conditions

Blastic Plasmacytoid Dendritic Cell Neoplasm; Myeloproliferative Disorders; Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Leukemia; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2017
• First Posted: December 29, 2017
• Study Start: January 2, 2018
• Primary Completion: September 6, 2023
• Study Completion (Estimated): December 30, 2026
• Last Updated: December 16, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); FR (5); US (15); ES (1); GB (1); IT (4)