The trial is taking place at:
F

Franciscan Health | Indiana Blood and Marrow Transplantation

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

I

ImmPACT Bio

Status and phase

Enrolling
Phase 2
Phase 1

Conditions

Relapsed Non-Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma

Treatments

Drug: IMPT-314

Study type

Interventional

Funder types

Industry

Identifiers

NCT05826535
MPCT-012L

Details and patient eligibility

About

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. Three cohorts of participants will be enrolled: 1) CAR T naïve after at least two or more prior lines of treatment, 2) CAR T experienced and 3) refractory disease or relapse within one year of first line therapy. Up to approximately 90 patients (30 per cohort) will be enrolled in dose finding Phase 1 part of the study, which will determine the recommended phase 2 dose. Phase 2 will enroll up to approximately 60 additional participants (20 per cohort) 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.

Enrollment

150 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No 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
  • DLBCL arising from follicular lymphoma (Transformed FL)
  • Primary mediastinal (thymic) large B-cell lymphoma
  • High-grade large B-cell lymphoma with or without MYC and BCL2 and/or BCL6 rearrangement
  • Grade 3b follicular lymphoma/Large cell follicular lymphoma

Received at least 1 prior line 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]). In participants who have only received front-line therapy, progression should be ≤12 months of initiating first-line therapy.
  • In patients who received two or more lines of therapy, refractory disease is defined as failure to achieve a CR to last line of therapy (including CAR T and/or salvage therapy).
  • In patients who received one line of therapy, refractory disease is defined as failure to achieve at least a PR after at least 4 cycles of therapy
  • 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 CNS disease is deemed stable at the time of study enrolment
  • History of cardiac lymphoma involvement
  • Ongoing or impending oncologic emergency (e.g., tumor mass effect, tumor lysis syndrome)

Received the following therapies in the specified time frame prior to enrollment/leukapheresis

Any systemic therapy within 2 weeks

Any systemic inhibitory/stimulatory immune checkpoint molecule therapy within 3 half-lives prior to enrollment (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-

1BB agonists)

  • Fludarabine within 12 weeks
  • Alemtuzumab, bendamustine or antithymocyte globuline (ATG) within 6 months
  • Any T cell engager/bispecific antibody therapy such as CD20/CD3 or CD19/CD3 bispecific antibodies within 4 weeks
  • Any experimental therapy within 4 weeks or 5 half-lives (whichever is shorter)
  • Received radiation therapy within 3 weeks prior to enrollment
  • Experiencing non-hematologic 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 or solid organ transplantation
  • Receipt of autologous stem cell transplantation within 6 weeks prior to enrollment
  • History of prior genetically modified T cell therapy other than a product targeting CD19 with an FMC63-based CAR (e.g., axicabtagene ciloleucel (axi-cel, YESCARTA®), tisagenlecleucel (tisa-cel, KYMRIAH®), or lisocabtagene maraleucel (liso-cel, BREYANZI®). For all other CAR T cell therapy treatments, discussion with the Sponsor's Medical Monitor is required
  • 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. Participants who have other autoimmune condition(s) considered to be associated with underlying malignancy may be enrolled in the study after discussion with and approval of the Medical Monitor.

Other protocol-defined criteria apply.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

Single Blind

150 participants in 9 patient groups

Phase I Dose Level I CAR T experienced cohort
Experimental group
Description:
Phase I 3+3 design Dose level 1: 1×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window
Treatment:
Drug: IMPT-314
Phase I Dose Level II CAR T experienced cohort
Experimental group
Description:
Phase I 3+3 design Dose level 2: 3×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window
Treatment:
Drug: IMPT-314
Phase II CAR T experienced cohort
Experimental group
Description:
Single dose determined during Phase I.
Treatment:
Drug: IMPT-314
Phase I Dose Level I CAR T naïve cohort
Experimental group
Description:
Phase I 3+3 design Dose level 1: 1×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window
Treatment:
Drug: IMPT-314
Phase I Dose Level II CAR T naïve cohort
Experimental group
Description:
Phase I 3+3 design Dose level 2: 3×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window
Treatment:
Drug: IMPT-314
Phase II CAR T naïve cohort
Experimental group
Description:
Single dose determined during Phase I.
Treatment:
Drug: IMPT-314
Phase I Dose Level I Refractory disease or relapse within one year of first line therapy
Experimental group
Description:
Phase I 3+3 design Dose level 1: 1×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window
Treatment:
Drug: IMPT-314
Phase I Dose Level II Refractory disease or relapse within one year of first line therapy
Experimental group
Description:
Phase I 3+3 design Dose level 2: 3×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window
Treatment:
Drug: IMPT-314
Phase II Refractory disease or relapse within one year of first line therapy
Experimental group
Description:
Single dose determined during Phase I.
Treatment:
Drug: IMPT-314

Trial contacts and locations

20

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Central trial contact

ImmPACT Bio

Data sourced from clinicaltrials.gov

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