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

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

1. Age 18 years or older

2. Willing and able to provide written informed consent

3. 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

4. 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

5. 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 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

6. 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

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

8. Absolute neutrophil count (ANC) ≥ 1000/uL

Other protocol-defined criteria apply.

Exclusion criteria

1. 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

2. Active central nervous system (CNS) involvement by malignancy on magnetic resonance imaging (MRI) or by lumbar puncture. Participants with prior evidence of brain metastasis 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

3. History of cardiac lymphoma involvement

4. Ongoing or impending oncologic emergency (e.g., tumor mass effect, tumor lysis syndrome)

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

   1. Any systemic therapy within 2 weeks

   2. 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)

   3. Fludarabine within 12 weeks

   4. Alemtuzumab, bendamustine or antithymocyte globuline (ATG) within 6 months

   5. Any T cell engager/bispecific antibody therapy such as CD20/CD3 or CD19/CD3 bispecific antibodies within 4 weeks

   6. Any experimental therapy within 4 weeks or 5 half-lives (whichever is shorter)

6. Received radiation therapy within 3 weeks prior to enrollment

7. Experiencing non-hematologic toxicities due to prior therapy (stable and recovered to grade ≤ 1 or non- clinically significant toxicities such as alopecia are allowed)

8. History of allogeneic stem cell or solid organ transplantation

9. Receipt of autologous stem cell transplantation within 6 weeks prior to enrollment

10. History of prior genetically modified 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

11. Primary immunodeficiency

12. 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

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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