Type: Oral
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Novel Approaches to Enhance Cellular Therapies and Immune Responses in Leukemias and Lymphomas
Hematology Disease Topics & Pathways:
Research, clinical trials, Hodgkin lymphoma, Biological therapies, Lymphomas, non-Hodgkin lymphoma, Bispecific Antibody Therapy, Clinical Research, Combination therapy, Diseases, Therapies, Lymphoid Malignancies, Natural Killer (NK) Cell Therapies
METHODS:
This investigator-initiated single-center phase I-II trial (NCT04074746) evaluated the safety and activity of P+E AFM13-precomplexed CB NK cells followed by systemic AFM13. Pts ages 15–75 with CD30+ lymphomas refractory to brentuximab vedotin were enrolled. The goals were to identify the recommended phase 2 dose (RP2D) of NK cells, estimate the overall (ORR) and complete response (CR), event-free (EFS) and overall survival (OS) rates, and study NK cell activation and persistence. Each treatment cycle consisted of fludarabine/cyclophosphamide (days −5 to −3) followed by infusion (day 0) of the AFM13-precomplexed CB NK cells, cultured for 14 days as described above, and three weekly IV infusions of AFM13 (200 mg, days 7, 14 and 21). Two cycles were planned for pts 1-19 and up to 4 cycles from patient 20 on. Response was evaluated on day 28 of each cycle. Enrollment proceeded at 3 dose levels (DL) of 106, 107 and 108 NK/Kg, respectively. Each patient received the same NK dose in all cycles.
RESULTS:
Between 09/20-12/22 we enrolled 42 pts (37 HL, 5 NHL), pretreated with a median 7 lines, at DL1 (N=3), DL2 (N=3) and DL3 (N=36), with 1 (N=2), 2 (N=21), 3 (N=3) or 4 cycles (N=16). All had active progressive disease at enrollment and no bridging therapy was given. The cords used for each of the 117 cycles were selected without consideration for HLA match, which was 0/6 (N=53), 1/6 (N=46), 2/6 (N=14), 3/6 (N=3) and 4/6 (N=1). The product infused consisted of >94% NK cells (expanded >2,700 fold), with only 0.02% T cells. The NK cells were 96% viable, 91% bound to AFM13, and 97.6% CD16+. The products were infused fresh.
There was 1 grade 2 infusion-related reaction (IRR) in 115 infusions of AFM13-NK (0.8%) and 27 IRR infusion related reactions in 350 infusions of AFM13 (7.7%) (1 G3, 26 G2). We saw no cases of CRS, ICANS or GVHD of any grade. DL3 (108 NK/Kg) was established as the RP2D. The ORR and CR were 92.8% and 66.7%, respectively (94.4% and 72.2%, respectively, in 36 pts treated at the RP2D). Nine pts had a response consolidated with SCT (5 allo, 4 auto).
At median follow-up of 14 (6-34) months, the EFS/OS rates are 31%/76%; median EFS/OS are 8 months/not reached. No relapses were associated with antigen loss. In the subset of pts planned for 4 cycles at RP2D, 15 of 23 pts remained event free at 6 mo (4 pts with and 11 without SCT consolidation), for 6-month EFS/OS rates of 65%/83%. Overall, 8 of the 9 pts (89%) receiving a consolidation SCT are event free at 10 to 34 months.
AFM-bound CB NK cells were detected in blood from day 1 post infusion for up to 3 weeks. Donor NK levels followed similar patterns after each cycle, which argues against a sensitization after the first NK infusion. CyTOF studies showed increased expression of AFM13 and activation markers in donor NK cells. We confirmed trafficking of AFM13-bound donor NK cells to tumor sites shortly after infusion.
CONCLUSIONS:
CB-derived cytokine-induced memory-like NK cells precomplexed with AFM13 have excellent tolerability and activity for pts with heavily pretreated and refractory CD30+ lymphoma.
Disclosures: Nieto: Affimed: Research Funding; Astra Zeneca: Research Funding; Secura Bio: Research Funding. Banerjee: Takeda: Patents & Royalties, Research Funding. Kerbauy: Takeda: Patents & Royalties. Basar: Affimed: Other: R. B. and The University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Affimed GmbH. ; Takeda: Other: R. B. and The University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Takeda Pharmaceutical. . Ahmed: ADC Therapeutics: Consultancy; Servier: Consultancy; Kite/Gilead: Consultancy; Chimagen: Research Funding; Genmab: Research Funding; Merck: Research Funding; Janssen: Research Funding. Srour: Orca Bio: Research Funding. Qazilbash: Amgen: Research Funding; Janssen: Research Funding; Angiocrine: Research Funding; NexImmune: Research Funding; Bioline: Other: Advisory board. Alexis: Affimed: Current Employment, Current holder of stock options in a privately-held company. Emig: Affimed: Current Employment, Current holder of stock options in a privately-held company. Harstrick: Affimed: Current Employment, Current holder of stock options in a privately-held company. Shpall: Adaptimmune: Membership on an entity's Board of Directors or advisory committees; NY Blood Center: Membership on an entity's Board of Directors or advisory committees; Axio: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: License agreement; Affimed: Other: License agreement; Syena: Other: License agreement; Celaid Therapeutics: Membership on an entity's Board of Directors or advisory committees; Fibrobiologics: Membership on an entity's Board of Directors or advisory committees; Navan: Membership on an entity's Board of Directors or advisory committees. Rezvani: Affimed: Other: License agreement; Takeda: Patents & Royalties.
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