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

Refractory Non-Hodgkin Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05826535
• Other study ID #: MPCT-012L
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 9, 2023
• Est. completion date: December 1, 2029

Study information

• Verified date: June 2024
• Source: ImmPACT Bio
• Contact: ImmPACT Bio
• Phone: 818-857-4828
• Email: clinicaltrials[@]immpact-bio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 1, 2029
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

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 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 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

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Refractory Non-Hodgkin Lymphoma
• Relapsed Non-Hodgkin Lymphoma

Intervention

Drug:
• IMPT-314
CAR T-cell therapy

Locations

Country	Name	City	State
United States	University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico
United States	Augusta University Medical Center	Augusta	Georgia
United States	St Luke's Cancer Institute	Boise	Idaho
United States	Montefiore Medical Center	Bronx	New York
United States	University of Vermont Cancer Center	Burlington	Vermont
United States	University of Cincinnati (UC) Physicians Company, LLC	Cincinnati	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Corewell Health	Grand Rapids	Michigan
United States	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	University of California-Irvine Medical Center	Irvine	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of California, Los Angeles (UCLA) Medical Center	Los Angeles	California
United States	University of Louisville Brown Cancer Center	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Virginia Commonwealth University-Massey Cancer Center	Richmond	Virginia
United States	University of California (UC) Davis Comprehensive Cancer Center	Sacramento	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Intermountain Healthcare	Salt Lake City	Utah
United States	Scripps Clinic	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
ImmPACT Bio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: Incidence of DLTs and other treatment-emergent adverse events (TEAEs)		Baseline to Month 24
Primary	Phase I: Investigator-assessed complete response (CR) rate		Baseline to Month 24
Primary	Phase I: Proportion of enrolled participants who receive the target dose		Baseline to Month 24
Primary	Phase II: Complete response based on investigator assessment per the Lugano classification		Baseline to Month 24
Secondary	Phase I and II: Proportion of enrolled participants with no prior exposure to T cell engagers who receive the target dose of IMPT-314		Baseline to Month 24
Secondary	Phase I and II: Proportion of enrolled participants with prior exposure to T cell engagers who receive the target dose of IMPT-314		Baseline to Month 24
Secondary	Phase I and II: Overall response rate (ORR)		Baseline to Month 24
Secondary	Phase I and II: Duration of response (DOR)		Baseline to Month 24
Secondary	Phase I and II: Duration of complete response (DOCR)		Baseline to Month 24
Secondary	Phase I and II: Progression free survival (PFS)		Baseline to Month 24
Secondary	Phase I and II: Overall survival (OS)		Baseline to Month 24
Secondary	Phase I and II: Cmax from time 0 to Day 28 (AUC0-28)		Baseline to Day 28
Secondary	Phase I and II: Area under the curve from time 0 to Day 28 (AUC0-28)		Baseline to Day 28
Secondary	Phase I and II: Persistence of IMPT-314 (Concentration of IMPT-314 cells in peripheral blood).		Baseline to Day 28
Secondary	Phase II: Incidence of TEAEs		Baseline to Month 24