P1, N=20, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial primary completion date: Apr 2024 --> Apr 2025

P2, N=108, Completed, Affimed GmbH | Active, not recruiting --> Completed

P1/2, N=240, Recruiting, Genmab | Trial completion date: Jun 2028 --> Dec 2032

AB-101 has demonstrated potent killing of tumor cell lines in vitro and in vivo, and preliminary results of a Phase 1/2 trial of AB-101 alone and in combination with rituximab in patients with R/R B cell non-Hodgkin lymphoma demonstrated AB-101 is well tolerated (Khanal et al...Patients aged ≥18 years are planned for enrolment and patients with R/R HL must have received at least two prior lines of therapy including prior combination chemotherapy, brentuximab vedotin (BV) and a checkpoint inhibitor...A run-in phase will assess two dose levels of AFM13 and AB-101 in 4 cohorts (Figure). A standard lymphodepletion regimen of fludarabine (30 mg/m2/day) and cyclophosphamide (300 mg/m2/day) will be administered IV from Day −5 to Day −3 at the start of each treatment cycle...In addition, an exploratory cohort (cohort 5) will begin enrolment of patients with CD30+ PTCL. Disease and efficacy assessments will be conducted at screening and on Day 43 (± 3 days) of each cycle.

Pts ages 15–75 with CD30+ lymphomas refractory to brentuximab vedotin were enrolled...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)... 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.

P2, N=154, Recruiting, Affimed GmbH | Not yet recruiting --> Recruiting

P1/2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Apr 2024 --> Apr 2025

P1/2, N=240, Recruiting, Genmab | Not yet recruiting --> Recruiting

P1/2, N=240, Not yet recruiting, Genmab

P2, N=154, Not yet recruiting, Affimed GmbH

A total of 108 patients (age 21–93; 61% male; mean prior lines was 2.7, [46.3% with brentuximab vedotin]) were enrolled; PTCL subtypes assessed were PTCL not‑otherwise‑specified, angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma, other. AFM13 continues to show robust single agent activity and a well-managed safety profile in patients with PTCLrefractory to standard therapy. The ORR is comparable to therapies approved for this indication, and subgroup analysis from this study suggests potential patient characteristics which may predict a more favorable response to AFM13. These data support further clinical development of AFM13, including in combination with allogeneic NK cells, to augment the innate immune response to CD30 + tumors.

Patients had received a mean of 2.7 prior treatment lines; 46.3% received prior brentuximab vedotin (BV), 17.6% received prior auto-transplant. AFM13 monotherapy demonstrated robust clinical activity in heavily pretreated patients with R/R PTCL. The safety profile of AFM13 was well managed and consistent with previously reported data from prior and ongoing clinical studies with AFM13. These data support future evaluation of AFM13 in combination with other immunotherapies, including allogeneic NK cells, to further potentiate anti-tumor immune responses to CD30+ lymphomas.

P1/2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Based on our data we hypothesize that CD16A shedding facilitates AFM13 induced ADCC potential of NK cells by allowing potent migration to distantly located tumor cells and serial killing. Especially in the context of AFM13 primary indications, Hodgkin and peripheral T cell lymphoma, migration of NK cells might have a particularly strong impact when treating cancer patients due to the disseminated nature of the disease.

Patients received a mean number of 2.7 prior treatment lines; 46.3% received prior brentuximab vedotin (BV), 17.6% received prior auto-transplant. AFM13 monotherapy was well managed and showed robust clinical activity in selected R/R PTCL subtypes. These data, together with encouraging preliminary efficacy seen in AFM13 combination studies in HL, support further evaluation of AFM13 in combination with NK cells to augment the innate immune response to CD30+ tumors.

P1, N=20, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial primary completion date: Jul 2023 --> Apr 2024

In the last decade, treatment regimen including brentuximab vedotin have significantly improved prognosis for patients with CD30-expressing lymphomas...Here, we report preclinical data for the novel DuoBody®-CD3xCD30 (GEN3017), a CD3 bsAb targeting CD30-expressing tumor cells...CD30-expressing HL (L428) and ALCL (KI-JK) tumor cell lines were incubated with purified healthy donor T cells (E:T ratio = 4:1) and DuoBody-CD3xCD30 or bsIgG1-CD3xctrl for 72 hours. T-cell mediated cytotoxicity was measured by flow cytometry and expressed as the percentage viable tumor cells normalized to an untreated control sample.

Patients aged 15–75 years with R/R CD30+ lymphomas refractory to brentuximab vedotin are enrolled...Each treatment cycle consisted of fludarabine/cyclophosphamide (days −5 to −3), followed by infusion of the AFM13-NK cells, cultured for 14 days as described above (day 0), and three weekly IV infusions of AFM13 (200 mg, days 7, 14 and 21)... This is the first clinical trial to date using an ICE® construct precomplexed with cytokine-induced memory-like CB-NK cells to treat patients with CD30+ R/R HL and NHL. Our preliminary results indicate that this ICE® precomplexed CB-NK cell therapy has an excellent tolerability profile and is highly active in patients with heavily pretreated R/R CD30+ lymphomas and warrants further investigation.

Here we describe the changes in metabolic tumor volume (MTV) total lesion glycolysis (TLG) and maximum standardized uptake value (SUVmax) after two cycles of therapies containing nivolumab brentuximab vedotin (Bv) or both in advanced cHL. We retrospectively enrolled subjects with newly diagnosed advanced stage cHL who received therapy in three protocols: Bv-nivolumab-AD Bv-AVD or nivolumab-AVD. This is the first report to describe PET-derived metabolic changes in advanced stage cHL patients receiving nivolumab and/or Bv-based regimens. Our initial results suggest a significant and comparable reduction in MTV TLG and SUVmax among the three treatment groups. The limited sample size did not confirm an initial observation of higher reductions in patients receiving Bv-based strategies.

P1/2, N=42, Not yet recruiting, Medical College of Wisconsin

In patients with relapse of classical Hodgkin lymphoma (cHL) after autologous stem cell transplant, brentuximab vedotin and anti-PD1 treatment, the outcome is poor. With an objective response rate (ORR) of 16.7% (1/5 in arm A, 1/11 in arm B, and 2/8 in arm C) and a 12-month progression-free survival (PFS) of 12.6% (95% CI 3.2-28.9), treatment efficacy of AFM13 monotherapy in all evaluable patients was modest. The continuous application schedule (arm C) might be more effective, but the visit schedule should be better aligned with patients' daily life.

P1/2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2023 --> Apr 2025 | Trial primary completion date: Apr 2023 --> Apr 2024

P1, N=20, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial primary completion date: Jul 2022 --> Jul 2023

P1/2, N=30, Recruiting, M.D. Anderson Cancer Center | Phase classification: P1 --> P1/2

According to preliminary results from a phase I/II trial, cord blood-derived natural killer cells complexed with AFM13, a bispecific antibody, showed efficacy in patients with relapsed/refractory CD30+ lymphomas. Complete responses were seen, and treatment was extremely well tolerated.

P1, N=20, Recruiting, UNC Lineberger Comprehensive Cancer Center | N=10 --> 20

No abstract available

After a lymphocyte-depleting chemotherapy with fludarabine and cyclophosphamide, 4 patients in cohort 1 and 3 patients in cohort 2 received 10/kg and 10/kg CAR-T cells, respectively, and 5 patients in cohort 3 received 10/kg CAR-T cells combined with anti-PD-1 antibody...Cytokine release syndrome (CRS) was observed in 4 of 12 patients, and only 1 patient (patient 9) experienced grade 3 CRS and was treated with glucocorticoid and tocilizumab...Three patients died last because of disease progression. Taken together, the combination of anti-PD-1 antibody showed an enhancement effect on CD30 CAR-T therapy in r/r CD30+ lymphoma patients with minimal toxicities.

Pts receive 2 cycles of fludarabine/cyclophosphamide (days −5 to −3) followed by AFM13-CB NK cells (day 0) and 3 weekly intravenous infusions of AFM13 (200 mg, days 7, 14 and 21). In conclusion, the preliminary results of this first clinical trial of ICE®-precomplexed NK cells for R/R CD30+ lymphoma indicate excellent tolerability and high activity and warrant further investigation of this approach. >

P2, N=145, Active, not recruiting, Affimed GmbH | Recruiting --> Active, not recruiting | Trial completion date: Feb 2023 --> Dec 2023 | Trial primary completion date: Apr 2022 --> Dec 2022

In the past decade, novel therapies including, brentuximab vedotin, PD-1 inhibitors, and the incorporation of PET-imaging into management have changed the paradigm of relapsed/refractory disease care. There is promising early work into the utility of CD30.CAR-T cell therapy, AFM13, camidanlumab tesirine, novel PD-1 inhibitors, and JAK1/JAK2 inhibition in management. Herein, we will review current salvage therapies in Hodgkin lymphoma and future directions in relapsed/refractory disease management.

P1, N=10, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Dec 2036 --> Jul 2037 | Trial primary completion date: Dec 2021 --> Jul 2022

Early clinical studies with AFM13 have demonstrated safety and efficacy, both as mono- and combination therapy with an anti-PD-1 checkpoint inhibitor (pembrolizumab) (Bartlett, N.L. et al., Blood 2020;136(21):2401–2409), in patients with relapsed or refractory (R/R) HL or peripheral T cell lymphoma (PTCL). More importantly, these assays demonstrate that the high ADCC potency and efficacy of NK cells, pre-complexed with CD16A-specific tetravalent ICE®, is maintained after one freeze-thaw cycle. These data suggest that high-affinity pre-complexing of adoptive NK cells with bispecific, CD16A-selective ICE® could be a novel cryopreserved off-the-shelf NK cell product for the effective depletion of tumor cells without the limitations and potential risks associated with the CAR-NK cell technology.

Early clinical studies with AFM13 have demonstrated safety and efficacy, both as mono- and combination therapy with an anti-PD-1 checkpoint inhibitor (pembrolizumab) (Bartlett, N.L. et al., Blood 2020;136(21):2401–2409), in patients with relapsed or refractory (R/R) HL or peripheral T cell lymphoma (PTCL). More importantly, these assays demonstrate that the high ADCC potency and efficacy of NK cells, pre-complexed with CD16A-specific tetravalent ICE®, is maintained after one freeze-thaw cycle. These data suggest that high-affinity pre-complexing of adoptive NK cells with bispecific, CD16A-selective ICE® could be a novel cryopreserved off-the-shelf NK cell product for the effective depletion of tumor cells without the limitations and potential risks associated with the CAR-NK cell technology.

Patients with mGCT who progressed after first line cisplatin-based chemotherapy and after at least 1 salvage regimen (high-dose or standard-dose chemotherapy) were eligible. 6 patients achieved radiographic stable disease (range, 9-14.9 weeks), 5 had elevated AFP or hCG at trial entry and all 5 had transient > 50% decline in baseline AFP/hCG: 4 had CD30 -ve and 2 had CD30 + ve staining; 10 patients had progression of disease as their best response; 2 were not evaluable for response. Conclusion Brentuximab vedotin does not appear to have clinically meaningful single-agent activity in patients with refractory GCT.

Good prognosis and response to treatment characterized C-ALCL with a ten-year-disease-free survival of ~90% very different from that of the systemic forms of ALCL (S-ALCL) . S-ALCL are classified as ALK (anaplastic lymphoma kinase) positive (+) or ALK negative (-) .

Heatmaps demonstrate the detection of checkpoint proteins in the conditioned media collected from human tumor cell lines and stimulated PBMCs. In summary, our results demonstrate that these two multiplex immunoassays we developed are useful research tools for the simultaneous quantitation of circulating immune checkpoint proteins, as well as for its potential application in biomarker discovery and translational research.

Emergency resuscitation with leukapheresis and treatment of tumour lysis syndrome along with supportive care should be followed by combination chemotherapy. Brentuximab vedotin and stem cell transplantation are the backbone of treatment for relapsed/refractory disease.

CD30 expression was only partial. The treatment was very well tolerated and allowed the patient to benefit from allogeneic hematopoietic stem cell transplantation.