Finally, in patient marrow specimens, CC-96191 eliminated AML cells but not normal monocytes, suggesting selectivity of TriNKET-induced cytotoxicity toward neoplastic cells. Together, these findings support the clinical exploration of CC-96191 as in NCT04789655.

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

P1, N=48, Recruiting, Beijing StarMab Biomed Technology Ltd | Initiation date: Aug 2023 --> Dec 2023

P1, N=50, Recruiting, Affimed GmbH

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.

P1, N=48, Recruiting, Beijing StarMab Biomed Technology Ltd

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

AFM28 induced NK cell activation at low picomolar concentrations and mediated efficacious and significant depletion of CD123+ blasts and LSCs in primary AML and HR-MDS samples. The ability to eradicate LSCs without seriously affecting normal hematopoiesis promises durable responses and the potential for long-term remission. A phase 1 dose-escalation study of AFM28 monotherapy (NCT05817058) has been initiated and the combination with allogenic NK cells is envisioned.

P1/2, N=85, Active, not recruiting, Affimed GmbH | Recruiting --> Active, not recruiting | N=155 --> 85 | Trial primary completion date: Apr 2024 --> Jul 2023

P1/2, N=148, Recruiting, Affimed GmbH | N=105 --> 148

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

N/A ADCC, Acute myeloid leukemia, NK cell, Immune therapy

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.

The novel mechanism of action of AFM24 may provide an alternative treatment approach for patients with EGFR+ solid tumors. In this study, AFM24 monotherapy was adequately tolerated in a heavily pretreated population of patients with EGFR+ CRC. AFM24 is also being investigated in combination with atezolizumab and autologous NK cells in various EGFR+ solid tumors.

AFM24 demonstrated clinical activity and acceptable safety in heavily pretreated patients with EGFR mutant NSCLC. The novel mechanism of action of AFM24 could add to the therapeutic options for patients with EGFR expressing tumors and is under clinical evaluation as a single agent and in combination with atezolizumab or autologous NK cells. Clinical trial information: NCT04259450.

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

AFVT-2101 was well-tolerated with no test article-related adverse effects on clinical observations, bodyweight, clinical chemistry, hematology, coagulation, anatomic pathology, or immunotoxicity parameters. The no observed adverse effect level (NOAEL) was determined to be 150 mg/kg under the conditions of the study.The safety profile is being further evaluated in an ongoing pivotal 4-week GLP study incorporating standard toxicology endpoints, safety pharmacology (CNS, CV, and respiratory), gross and anatomic pathology, as well as cytokine, immunophenotyping, receptor occupancy, TK, and ADA analyses.In conclusion, AFVT-2101 is well-tolerated in NHPs with a pharmacokinetic and safety profile consistent with its intended clinical application.

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.

AFM28 induced highly potent and selective lysis of CD123+ leukemic cells, including LSCs and progenitor cells, by allogeneic NK cells. The capacity to eradicate LSCs could increase the frequency and durability of responses, induce long-term remission, and prevent disease relapse after conventional treatment or aSCT in patients with AML. A first-in-human clinical investigation of AFM28 is being initiated.

RO7297089 was well tolerated at doses up to 1850 mg, and the efficacy data supported activity of RO7297089 in multiple myeloma. Combination with other agents may further enhance its potential as an innate immune cell engager in multiple myeloma.

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.

Clinical activity was observed in two patients. Dose escalation is proceeding at 480 mg and enrollment has begun.

T cells are activated within the periphery, and T cell numbers increase in tumors, which may indicate stimulation of anti-cancer activity of the adaptive immune system as an indirect effect of AFM24. Clinical and correlative science from the escalation phase of the study supports further investigation of AFM24 anti-tumor activity in EGFR-expressing tumor-specific cohorts.

P1/2, N=105, Recruiting, Affimed GmbH | Trial completion date: Sep 2024 --> Jun 2025 | Trial primary completion date: Jan 2023 --> Sep 2024

P1/2, N=155, Recruiting, Affimed GmbH | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Sep 2022 --> Apr 2024

Based on model simulations, we propose more frequent dosing of RO7297089 compared to regular monthly frequency in the clinic at the beginning of treatment to ensure sustained target engagement. This study demonstrates a translational research strategy for collecting relevant nonclinical data, establishing a TMDD model, and using simulations from this model to inform clinical dose regimens.

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

Early biomarker data demonstrate target engagement with expected immune activation. Studies are also evaluating AFM24 in combination with atezolizumab, or with autologous NK cells exploring its potential to activate the innate immune response.

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.

No abstract available

Efficacy will also be assessed by assessing progression-free and overall survival. Secondary endpoints for both phases include treatment-emergent adverse events, serious adverse events, pharmacokinetics and immunogenicity.

The Phase 2a study will then establish the overall response rate (as per RECIST v1.1) and safety of combination therapy in patients with advanced/ metastatic, or treatment refractory gastric, esophagogastric, hepatocellular, hepatobiliary, pancreatic, or non-small cell lung cancer. For both phases, secondary endpoints include treatment-emergent adverse events, serious adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity.

P1/2, N=155, Recruiting, Affimed GmbH | Trial primary completion date: Apr 2022 --> Sep 2022