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

• Status: Not yet recruiting
• Trial end date: 2029-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ImmPACT Bio

Criteria

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 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

4. 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

5. 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

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 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

3. History of cardiac lymphoma involvement

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

5. 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)

6. Received radiation therapy within 3 weeks prior to enrollment

7. Experiencing 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 transplantation

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

10. History of prior CAR therapy or other genetically modified T cell therapy

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

Other protocol-defined criteria apply.