-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

774 Innate Cell Engager (ICE®) AFM13 Combined with Preactivated and Expanded (P+E) Cord Blood (CB)-Derived Natural Killer (NK) Cells for Patients with Refractory CD30-Positive Lymphomas: Final Results

Program: Oral and Poster Abstracts
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
Monday, December 11, 2023: 11:45 AM

Yago Nieto, MD, PhD1, Pinaki Banerjee, PhD2*, Indreshpal Kaur, PhD2*, Lori Griffin2*, Melissa Barnett2*, Christina Ganesh2*, Zephanie Borneo2*, Roland L. Bassett, MS3*, Lucila Nassif Kerbauy, MD, PhD2, Rafet Basar, MD2*, Mecit Kaplan2, Daniel Esqueda2*, Jeremy Ramdial, MD2, Sairah Ahmed, MD4, Chitra Hosing, MD2, Samer A. Srour, MD2, Amin Alousi2*, Muzaffar H. Qazilbash, MD2, Raphael Eric Steiner, MD5, Karenza Alexis6*, Michael Emig, MD7*, Andreas Harstrick7*, Elizabeth J. Shpall, MD2 and Katy Rezvani, MD8

1Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston
2Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
4Department of Lymphoma/Myeloma and Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX
5Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston
6Affimed Inc., Heidelberg, Germany
7Affimed GmbH, Heidelberg, Germany
8Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M D Anderson Cancer Center, Houston, TX

Pts with refractory Hodgkin (HL) and other CD30+ lymphomas have few effective therapies available and targeted NK cell immunotherapy is an active area of research. Transfer of non-targeted NK cells has shown limited clinical benefit as target recognition of cancer cells by NK cells constitutes a barrier. The innate cell engager AFM13 is a first-in-class CD30/CD16A bispecific antibody construct that induces selective killing of CD30+ tumor cells by engaging and activating NK cells. As a single agent, AFM13 has limited clinical activity against HL, likely due to the reduced effector function of autologous NK cells in these pts, which provides the rationale for combining AFM13 with allogeneic NK cells. Our prior preclinical work identified a promising combination of CB-derived NK cells that were first IL-12/IL-15/IL-18-preactivated followed by ex vivo expansion (P+E) with engineered K562 feeder cells expressing membrane-bound IL-21, 4-1BBL and CD48 and exogenous IL-2, and subsequently complexed with AFM13 just before infusion; these cytokine-induced memory-like NK cells presented chimeric antigen receptor (CAR)-NK-like features and increased in vitro and in vivo antitumor activity compared to either non-AFM13-precomplexed P+E NK cells or to AFM13 alone (Kerbauy et al, Clin Cancer Res 2021). Building on this work we wished to study this CB NK-cell therapy in pts with refractory CD30+ lymphomas.

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.

<< Previous Abstract | Next Abstract
*signifies non-member of ASH