Study of IMPT-314 in R/R Aggressive B-cell

Sponsor

ImmPACT Bio (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05826535

Collaborator

(none)

Enrollment

Locations

Arms

79.7

Anticipated Duration (Months)

12.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of IMPT-314, a bispecific chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with aggressive B-cell NHL.

Up to 30 patients will be enrolled in dose finding Phase 1 part of the study, which will determine the recommended phase 2 dose.

Phase 2 will enroll 20 additional participants to evaluate further the safety and efficacy of IMPT-314.

IMPT-314 treatment consists of a single infusion of CAR-transduced autologous T cells administered intravenously after a conditioning chemotherapy regimen consisting of fludarabine and cyclophosphamide, administered over 3 days.

Individual participants will remain in the active post-treatment period for approximately 2 years. Participants will continue in long-term follow-up for 15 years from treatment.

Condition or Disease	Intervention/Treatment	Phase
Relapsed Non-Hodgkin Lymphoma Refractory Non-Hodgkin Lymphoma	Drug: IMPT-314	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Dose finding Phase I followed by a single group Phase II part. Two Phase I dose levels and one Phase II dose level.Dose finding Phase I followed by a single group Phase II part. Two Phase I dose levels and one Phase II dose level.

Masking:

Single (Outcomes Assessor)

Masking Description:

Analysis of response will be performed by Blinded Independent Central Review (BICR) Discordance between the Investigator assessment and BICR assessment will be evaluated for each efficacy endpoints based on tumor assessments if BICR assessments are performed.

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Multi-center Study Evaluating the Safety and Efficacy of IMPT-314, a CD19/20 Bispecific Chimeric Antigen Receptor (CAR) T Cell Therapy in Participants With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin Lymphoma

Anticipated Study Start Date :

Apr 12, 2023

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Dec 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase I Dose Level I cohort Phase I 3+3 design Dose level 1: 1×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window	Drug: IMPT-314 CAR T-cell therapy
Experimental: Phase I Dose Level II cohort Phase I 3+3 design Dose level 2: 3×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window	Drug: IMPT-314 CAR T-cell therapy
Experimental: Phase II single group Single dose determined during Phase I.	Drug: IMPT-314 CAR T-cell therapy

Arm

Intervention/Treatment

Experimental: Phase I Dose Level I cohort

Phase I 3+3 design Dose level 1: 1×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window

Drug: IMPT-314

CAR T-cell therapy

Experimental: Phase I Dose Level II cohort

Phase I 3+3 design Dose level 2: 3×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window

Drug: IMPT-314

CAR T-cell therapy

Experimental: Phase II single group

Single dose determined during Phase I.

Drug: IMPT-314

CAR T-cell therapy

Outcome Measures

Primary Outcome Measures

Phase I: Incidence of DLTs and other treatment-emergent adverse events (TEAEs) [Baseline to Month 24]
Phase I: Investigator-assessed complete response (CR) rate [Baseline to Month 24]
Phase I: Proportion of enrolled participants who receive the target dose [Baseline to Month 24]
Phase II: Complete response based on investigator assessment per the Lugano classification [Baseline to Month 24]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 years or older
Willing and able to provide written informed consent
Histologically confirmed aggressive NHL, including the following types defined by the

World Health Organization (WHO) 2017:

DLBCL not otherwise specified (NOS)
DLBCL arising from follicular lymphoma
Primary mediastinal (thymic) large B-cell lymphoma
High-grade large B-cell lymphoma with or without MYC and BCL2 and/or BCL6 rearrangement

Received at least 2 prior lines of therapy. Prior therapy must have included:

Anti-CD20 monoclonal antibody
An anthracycline containing chemotherapy regimen
Participants with TFL must have received at least one of their prior lines of therapy after transformation to DLBCL

Relapsed or refractory disease, defined by the following:

Disease progression after last regimen (including salvage therapy after autologous stem cell transplantation [ASCT]), or
Refractory disease is defined failure to achieve a PR or CR to the last regimen

At least 1 measurable lesion (the Lugano classification). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Absolute neutrophil count (ANC) ≥ 1000/uL

Other protocol-defined criteria apply.

Exclusion Criteria:

History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease-free for at least 3 years. Participants who have received therapy for a prior malignancy within the prior 3 years, e.g., in the adjuvant setting, are not excluded
Active central nervous system (CNS) involvement by malignancy on magnetic resonance imaging (MRI) or by lumbar puncture. Participants with prior evidence of brain metastasis successfully treated at least 8 weeks prior to enrollment will not be excluded for participation if they are deemed under control at the time of study enrollment
History of cardiac lymphoma involvement
Ongoing or impending oncologic emergency (e.g., tumor mass effect, tumor lysis syndrome)
Received any systemic therapy within two weeks prior to enrollment/leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy. Received any systemic inhibitory/stimulatory immune checkpoint molecule therapy within less than 3 half-lives prior to enrollment (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4- 1BB agonists)
Received radiation therapy within 3 weeks prior to enrollment
Experiencing toxicities due to prior therapy (stable and recovered to grade ≤ 1 or non- clinically significant toxicities such as alopecia are allowed)
History of allogeneic stem cell transplantation
Receipt of autologous stem cell transplantation within 6 weeks prior to enrollment
History of prior CAR therapy or other genetically modified T cell therapy
Primary immunodeficiency
History of autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years

Other protocol-defined criteria apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles (UCLA) Medical Center	Los Angeles	California	United States	90095
2	University of Iowa	Iowa City	Iowa	United States	52242
3	University of Cincinnati (UC) Physicians Company, LLC	Cincinnati	Ohio	United States	45267
4	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112