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

• ClinicalTrials.gov Identifier: NCT03386513
• Recruitment Status: Active, not recruiting
• First Posted: December 29, 2017
• Last Update Posted: August 3, 2023
• Sponsor: ImmunoGen, Inc.
• Information provided by (Responsible Party): ImmunoGen, Inc.

Tracking Information

• First Submitted Date: December 21, 2017
• First Posted Date: December 29, 2017
• Last Update Posted Date: August 3, 2023
• Actual Study Start Date: January 2, 2018
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 17, 2021)

To assess the rate of composite CR in BPDCN patients [ Time Frame: 21-day cycle ]

CR+clinical CR [CRc]

Original Primary Outcome Measures (submitted: December 28, 2017)

Maximum Tolerated Dose (MTD) and recommended Ph2 dose (RP2D) [ Time Frame: 28 Days ]

To determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of IMGN632 when administered as a single agent

Current Secondary Outcome Measures (submitted: March 17, 2021)

• To assess the duration of CR (DOCR) for patients with CR or CRc [ Time Frame: Up to 24 months ]
• Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Up to 24 months ]
• To assess the rate of CR+CRc+CRh [ Time Frame: Up to 24 months ]
• To assess the duration of CR+CRc+CRh [ Time Frame: Up to 24 months ]
• To assess ORR: CR+CRc+CRh+CRi+PR [ Time Frame: Up to 24 months ]
• To assess the duration of overall response [ Time Frame: Up to 24 months ]
• To assess OS [ Time Frame: Up to 24 months ]
• To assess the percent of BPDCN patients able to bridge to stem cell transplant in the frontline and relapsed/refractory populations separately [ Time Frame: Up to 24 months ]
• To characterize the PK of IMGN632, total antibody, and FGN849 (the active catabolite) [ Time Frame: Up to 24 months ]
• To evaluate the potential immunogenicity of IMGN632 [ Time Frame: Up to 24 months ]
  ADA
• To assess transfusion independence [ Time Frame: Up to 24 months ]
  Conversion rate to independence of red blood cell (RBC) and platelet transfusion relative to baseline

Original Secondary Outcome Measures (submitted: December 28, 2017)

• Treatment emergent adverse events [ Time Frame: Up to 12 months ]
• Objective Response Rate (ORR) (complete response [CR= CR+CRp+CRi]+partial remission [PR]) [ Time Frame: Up to 12 months ]
• PK parameters: maximum plasma concentration (Cmax) of IMGN632 [ Time Frame: Up to 12 months ]
• PK parameters: area under the time-concentration curve (AUC) of IMGN632 [ Time Frame: Up to 12 months ]
• PK parameters: terminal half-life (t½) of IMGN632 [ Time Frame: Up to 12 months ]
• Immunogenicity: Presence of Antibody-Drug Antibody (ADA) [ Time Frame: Up to 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN
• Official Title: A Phase 1/2, Multi-center, Open-label Study of IMGN632 Monotherapy Administered Intravenously in Patients With CD123-positive Acute Myeloid Leukemia and Other CD123-positive Hematologic Malignancies
• 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.
• Detailed Description: IMGN632 is administered by IV on Day 1 of each cycle, with cycles repeating every 21 days.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Blastic Plasmacytoid Dendritic Cell Neoplasm
• Myeloproliferative Neoplasm

Intervention

Drug: IMGN632

CD123-targeted ADC

Study Arms

Experimental: Escalation and Expansion

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.

Intervention: Drug: IMGN632

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 1, 2023): 179
• Original Estimated Enrollment (submitted: December 28, 2017): 155
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 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.

2. Expansion inclusion:

   • 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.

Exclusion Criteria:

1. Participants who, in the judgment of their treating physician, have appropriate standard of care therapies will be excluded from Cohorts 1 through 5.
2. 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.
3. Participants with a history of veno-occlusive disease (sinusoidal obstruction syndrome) of the liver.
4. 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.
5. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Italy, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03386513
• Other Study ID Numbers: IMGN632-0801
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: ImmunoGen, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ImmunoGen, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Patrick Zweidler-McKay, MD; ImmunoGen, Inc.

• PRS Account: ImmunoGen, Inc.
• Verification Date: August 2023