On November 8, 2021 Affimed N.V. (Nasdaq: AFMD) and NKGen Biotech, both clinical stage biotech companies focused on harnessing the power of the body’s innate immune system, reported the initiation of patient recruitment in the open-label, multi-center phase 1/2a study (NCT05099549) evaluating the safety, tolerability, and anti-tumor activity of the innate cell engager (ICE) AFM24 (Affimed’s tetravalent, bispecific epidermal growth factor receptor (EGFR)- and CD16A-binding ICE) in combination with SNK01 (ex vivo expanded and activated autologous NK cell therapy from NKGen Biotech) (Press release, NKMax America, NOV 8, 2021, View Source [SID1234594731]).

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The objective of the phase 1 dose escalation is to evaluate safety and tolerability data for escalating AFM24 doses in combination with a fixed dose of SNK01 and to determine the maximum tolerated and recommended phase 2 dose for the expansion phase. Phase 2a will investigate additional tolerability, safety and anti-tumor activity. The trial will include patients with non-small cell lung cancer (NSCLC, EGFR-wildtype), squamous cell carcinoma of the head and neck (SCCHN), as well as patients with microsatellite instability (MSI) low/DNA mismatch repair proficient colorectal cancer (CRC) regardless of KRAS mutational status.

"Existing therapeutics that target EGFR rely on inhibiting EGFR signaling, an approach that has been hampered by intrinsic and acquired resistance mechanisms," said Dr. Anthony El-Khoueiry, Phase I Program Director at the USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC. El-Khoueiry is also associate professor of clinical medicine, Keck School of Medicine of USC and principal investigator for the study. "The combination of AFM24 with SNK01 represents a novel approach to leverage EGFR expression in multiple solid tumor types and optimally engage the innate immune system; this may be especially beneficial for patients with an impaired immune system or low NK cell numbers."

The clinical study is supported by preclinical data generated through the collaboration of Affimed and NKGen Biotech, including data that were recently presented at the AACR (Free AACR Whitepaper)-NCI-EORTC conference on Molecular Targets and Cancer Therapeutics. In the preclinical studies, AFM24 demonstrated robust binding to SNK01 cells and enhancement of the cytotoxic activity of SNK01 cells towards EGFR-positive A-431 cells, compared to untargeted SNK01 cells. In addition, markers for NK cell degranulation and intracellular IFNγ were increased in the combined therapy, indicating increased anti-tumor activity.

The AACR (Free AACR Whitepaper)-NCI-EORTC conference presentation may be found at: View Source and View Source

About AFM24

AFM24 is a tetravalent, bispecific innate cell engager (ICE) that activates the innate immune system by binding to CD16A on innate immune cells and EGFR, a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

In addition to the AFM24-103 study presented here, Affimed is evaluating AFM24 as a monotherapy (AFM24-101) for patients with advanced EGFR-expressing solid malignancies whose disease has progressed after treatment with previous anticancer therapies. The first-in-human phase 1/2a open-label, non-randomized, multi-center, multiple ascending dose escalation and expansion study and can be found at www.clinicaltrials.gov using the identifier NCT04259450.

About SNK01

SNK01 is a cell-based, patient-specific, ex vivo expanded and activated autologous NK cell therapy agent, manufactured from the patient’s leukapheresis or whole blood. NK cells are a subset of cytotoxic lymphocytes with the ability to directly attack virally infected cells or cancer cells and carry out immunoregulatory functions by the secretion of cytokines and chemokines.