Open Actively Recruiting

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

About

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. Two cohorts of participants will be enrolled: 1) CAR T naïve and 2) CAR T experienced.

Up to approximately 60 patients (15 per dose level 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 40 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.
Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase I/II

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
18 Years
Maximum Age
N/A

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 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)
    • Bendamustine or fludarabine within 12 weeks
    • Alemtuzumab or antithymocyte globuline (ATG) within 6 months
  • 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 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®)
  • 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.

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Study Stats
Protocol No.
23-000011
Category
Lymphoma
Contact
Christopher Hannigan
Location
  • UCLA Santa Monica
  • UCLA Westwood
For Providers
NCT No.
NCT05826535
For detailed technical eligibility, visit ClinicalTrials.gov.