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

Sponsor

ImmunoGen, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03386513

Collaborator

(none)

252

Enrollment

Locations

Arm

58.9

Anticipated Duration (Months)

16.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

The study is enrolling a pivotal cohort of frontline BPDCN patients and a cohort of relapsed/refractory BPDCN patients.

Condition or Disease	Intervention/Treatment	Phase
Blastic Plasmacytoid Dendritic Cell Neoplasm Acute Myeloid Leukemia Acute Lymphocytic Leukemia Myeloproliferative Neoplasm	Drug: IMGN632	Phase 1/Phase 2

Detailed Description

The study completed a dose escalation phase, and is now enrolling in a dose expansion phase to further characterize the safety profile and to assess the efficacy of IMGN632 in patients with BPDCN. IMGN632 is administered by IV on Day 1 of each cycle, with cycles repeating every 21 days.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

252 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 2, 2018

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Escalation and Expansion Escalation: IMGN632 was administered by IV on 2 different schedules for patients with relapsed/refractory AML or BPDCN. Expansion: the study is currently enrolling in 2 BPDCN expansion cohorts at the RP2D: Cohort 1: Relapsed or refractory BPDCN patients 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 6: Pivotal cohort for frontline BPDCN patients who have not received prior systemic therapy. Patients may have received local therapy (radiotherapy, surgical excision, photodynamic therapy). Eligible patients must have a recurrence or progression in the field of local therapy OR disease outside the field of local therapy. Other expansion cohorts not currently enrolling: • 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	Drug: IMGN632 CD123-targeted ADC

Arm

Intervention/Treatment

Experimental: Escalation and Expansion

Escalation: IMGN632 was administered by IV on 2 different schedules for patients with relapsed/refractory AML or BPDCN. Expansion: the study is currently enrolling in 2 BPDCN expansion cohorts at the RP2D: Cohort 1: Relapsed or refractory BPDCN patients 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 6: Pivotal cohort for frontline BPDCN patients who have not received prior systemic therapy. Patients may have received local therapy (radiotherapy, surgical excision, photodynamic therapy). Eligible patients must have a recurrence or progression in the field of local therapy OR disease outside the field of local therapy. Other expansion cohorts not currently enrolling: • 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

Drug: IMGN632

CD123-targeted ADC

Outcome Measures

Primary Outcome Measures

To assess the rate of composite CR in BPDCN patients [21-day cycle]
CR+clinical CR [CRc]

Secondary Outcome Measures

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]
To assess the duration of overall response [Up to 24 months]
To assess OS [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 [Up to 24 months]
To characterize the PK of IMGN632, total antibody, and FGN849 (the active catabolite) [Up to 24 months]
To evaluate the potential immunogenicity of IMGN632 [Up to 24 months]
ADA
To assess transfusion independence [Up to 24 months]
Conversion rate to independence of red blood cell (RBC) and platelet transfusion relative to baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Disease Characteristics:

Confirmation of CD123 positivity by flow cytometry or IHC. Patients who received prior CD123-targeting agents will be allowed as long as the blasts still have detectable CD123 expression.

Expansion inclusion:

Cohort 1 - Patients with relapsed or refractory BPDCN with 1-3 prior lines of therapy
Cohort 2 - Patients will have relapsed AML.
Cohort 3 - Patients will have relapsed or refractory ALL (including any subtypes: B-cell, T-cell, Ph+, and Ph-).
Cohort 4 - Patients will have relapsed or refractory "other" hematologic malignancies not included in the cohorts above (eg, high-risk/very high-risk MDS, MPN, CMML, BP- CML). Other CD123+ malignancies may be considered upon discussion with the Sponsor.
Cohort 5 - Patients will have relapsed or refractory (to non-intense therapies) AML.
Cohort 6 - Patients with frontline BPDCN who have not received prior systemic therapy.

Note: Patients in Cohort 6 may have received local therapy (radiotherapy, surgical excision, photodynamic therapy). Eligible patients must have a recurrence or progression in the field of local therapy OR disease outside the field of local therapy.

Exclusion Criteria:

Patients who, in the judgment of their treating physician, have appropriate standard of care therapies will be excluded from Cohorts 1 through 5.
Frontline BPDCN patients 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 patients 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.
Patients with a history of veno-occlusive disease of the liver.
Patients 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 patients with prior local therapy (eg, radiotherapy), patients must not have received treatment within 14 days prior to drug administration on this study. 2. Relapsed or refractory BPDCN patients 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. Patients must have recovered to baseline from all acute toxicity from this prior therapy.

Note: the exception that patients who have received a checkpoint inhibitor must not have received that therapy within 28 days prior to drug administration on this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Health MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
2	City of Hope Medical Center	Duarte	California	United States	91010
3	Moffitt Cancer Center	Tampa	Florida	United States	33612
4	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
6	Duke Cancer Institute	Durham	North Carolina	United States	27710
7	Baylor Scott & White University Medical Center	Dallas	Texas	United States	75246
8	MD Anderson Cancer Center	Houston	Texas	United States	77030-7095
9	Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
10	Recherche Clinique-Hématologie	Amiens		France
11	CHU de Besancon, Hopital Jean Minjoz	Besançon		France	25030
12	Hôpital St Antoine	Paris		France
13	Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola		Italy	47014
14	Instituto Europeo di Oncologia	Milano		Italy	20141
15	Hospital Universitari I Politècnic La Fe	Valencia		Spain	46026