Type: Oral
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Expanding Disease Targets for CAR-T Cell Therapies
Hematology Disease Topics & Pathways:
clinical trials, adult, Biological therapies, Research, Lymphomas, non-Hodgkin lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, B Cell lymphoma, Clinical Research, Diseases, aggressive lymphoma, Therapies, Lymphoid Malignancies, Human, Study Population, Minimal Residual Disease
Study Design and Methods: Our study is a phase 1, single center, open label, therapeutic trial. PMB-CT01 is a TN/SCM-enriched BAFFR.41BB.z.EGFRt-CAR T cell therapy which was previously described (Qin et al. Sci Transl Med. 2019). There are 3 dose levels (DL) in the dose escalation phase including 50x106 (DL1), 200x106 (DL2), and 600x106 (DL3) CAR T cells. The lymphodepletion regimen consists of cyclophosphamide 500 mg/m2/day and fludarabine 30 mg/m2/day for 3 days.
The primary endpoints are the incidence of adverse events and the determination of the maximum tolerated dose. Secondary endpoints include disease response, incidence of negative minimal residual disease (MRD), progression-free survival, and overall survival. ASTCT consensus criteria are used to grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Responses are determined by Lugano 2014 (Cheson et al., JCO 2014).
Results: As of July 19, 2023, three patients were enrolled and all received treatment at DL1, 50x106 PMB-CT01(BAFFRCAR T cells). The median age was 56 years old (41-75), 100% male. Patients #1 and #2 had MCL and both had received prior treatment with BTK inhibitors, and progressed after CD19CAR T cell therapy. Both patients had bone marrow involvement prior to treatment, and had 4 and 10 prior lines of therapy, respectively. Patient #3 with T cell/histiocyte-rich B cell lymphoma had received 3 prior lines of therapy and his lymphoma was negative for both CD19 and CD20. All 3 patients developed grade 1 CRS only. All CRS events resolved with 2 doses of tocilizumab given to patient #1 and 1 dose to patient #2. Patients #1 and #2 also developed grade 1 ICANS which were self-limited and resolved without pharmacologic intervention. No dose-limiting toxicity (DLT) was observed. Infection was seen in patient #2 with viral pneumonia at month 3.
All 3 treated patients responded to treatment. The overall response rate was 100% including MRD-negative complete response (CR) by flow cytometry and next-generation sequencing (NGS) in patient #1 and by flow cytometry in patient #2, and partial response (PR) in patient #3. All responses are ongoing at 8 months (patient #1), 4 months (patient #2) and 1.5 months (patient #3), respectively. Figure 1 shows the clearance of lymphoma cells in the bone marrow of the first patient 28 days post- CAR T cell infusion. Robust CAR T cell expansion was observed in all 3 patients with peak of expansion (between 2.1x106 and 8.9x106 copies/ml of blood) on day 12 (patient #1) and day 14 (patients #2 and #3) (Figure 1).
Conclusions: PMB-CT01(BAFFRCAR T cell) treatment at DL1 was safe and demonstrated potent anti-lymphoma activity with a 100% ORR (2 CR, 1 PR) in patients with poor prognosis. CRS and ICANS were all grade 1 and reversible. Enrollment is ongoing at DL2, and additional clinical and correlative analyses will be presented at the meeting.
Disclosures: Budde: Merck: Research Funding; Amgen: Research Funding; ADC Therapeutics: Consultancy; Roche: Consultancy; AstraZeneca: Consultancy, Research Funding; Novartis, Gilead, F. Hoffmann-La Roche Ltd, BeiGene, Genentech, Inc.: Consultancy; MustangBio: Research Funding. Baird: Genentech-Roche: Research Funding; Regeneron Pharmaceuticals: Research Funding; Kite Pharma-Gilead: Research Funding, Speakers Bureau; Cellular Biomedicine Group: Research Funding. Kambhampati: ADC Therapeutics: Research Funding; Genentech: Research Funding; Genmab: Research Funding. Cheng: PeproMene Bio. Inc: Current Employment. Kwak: PeproMene Bio. Inc: Consultancy, Current equity holder in private company.