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Design and rationale of the phase 1/2a open label, multicenter study of the AFM24 monotherapy in patients with advanced EGFR-expressing solid tumors
Design and rationale of the phase 1/2a study of AFM24 in combination with atezolizumab in patients with advanced EGFR-expressing solid tumors
Design and rationale of the phase 1/2a study of AFM24 in combination with SNK01 autologous natural killer cells in patients with advanced EGFR-expressing solid tumors
HEIDELBERG, Germany, May 26, 2022 (GLOBE NEWSWIRE) -- Affimed N.V. (Nasdaq: AFMD), (“Affimed”, or the “Company”), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, announced today that three abstracts of clinical trial designs of its AFM24 innate cell engager (ICE®) have been published and will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, taking place on June 3-7, 2022 in Chicago, IL.
"We recognize the challenges in treating EGFR-expressing solid tumors and believe our broad approach in developing AFM24 is an important step in finding alternative treatments for the many patients suffering from severe cancers that have progressed after treatment with current therapies,” said Dr. Andreas Harstrick, Chief Medical Officer at Affimed. “We are very excited to have these trial designs showcased at ASCO illustrating why we believe AFM24 can provide a promising alternative to current treatments.”
The Trial in Progress posters provide background information and introduce the study designs of the three ongoing AFM24 studies in which patients with a variety of EGFR-positive solid tumors are treated with AFM24 monotherapy or in combinations with either Roche’s checkpoint inhibitor, atezolizumab, or NKGen Biotech’s autologous NK cell product, SNK01.
Affimed’s ICE® molecules are tetravalent, bispecific and therefore can bind to tumor cell-surface antigens and CD16A expressed on natural killer (NK) cells and macrophages, inducing antibody-dependent cellular cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP), respectively.
AFM24 activates the innate immune system to kill cancer cells by binding to CD16A on innate immune cells and EGFR, a protein widely expressed on solid tumors.
Details about the Abstracts
The AFM24 monotherapy study (NCT04259450) abstract includes information about the dose-escalation phase of the study.
AFM24 utilizes the patient’s innate immunity to redirect and activate immune cells, overcoming resistance to current therapies. The primary mode of action of AFM24 is to redirect NK cells and macrophages to EGFR+ tumor cells inducing antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis, respectively. Preclinical studies showed AFM24 induced killing of EGFR+ tumor cell lines independent of EGFR expression level and independent of mutations in the EGFR signaling pathway. In vivo studies in cynomolgus monkeys demonstrated a favourable safety profile.
An ongoing phase 1/2a, first-in-human study is evaluating AFM24 in patients with locally advanced or metastatic, treatment refractory solid tumors that are known to express EGFR. The phase 1 dose escalation study was designed to establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of AFM24 and evaluate the safety, efficacy, immunogenicity, pharmacokinetic (PK) and pharmacodynamic (PD) responses.
AFM24 was administered intravenously once weekly until disease progression, intolerable toxicity, patient withdrawal, or termination of treatment at investigator’s discretion. AFM24 had a well-managed safety profile and the RP2D was established at 480 mg.
In parallel to the continuing dose escalation phase (cohort 7 at 720 mg), a phase 2a dose expansion study was initiated, and the first patient was enrolled in January 2022. This Simon two-stage study will assess AFM24 at the RP2D in patients with different EGFR-expressing tumors. The trial will progress to the second stage unless the null hypothesis, that the true tumor response rate is below a specific value, is confirmed at the end of stage one.
Eligible patients must have positive histological or cytological staining of EGFR in >1% of tumor cells. The primary endpoint of the study is to establish the overall response rate in three disease-specific cohorts. These include patients with clear cell renal cell carcinoma (ccRCC), KRAS wild-type colorectal cancer (KRASwt CRC) and EGFR-mutant non-small cell lung cancer (EGFRmut NSCLC). Secondary endpoints include treatment-emergent adverse events, serious adverse events, PK, PD, and immunogenicity.
Authors: Omar Saavedra Hadea, Elena Garralda, Juanita Suzanne Lopez, Mark M. Awad, Jacob Stephen Thomas, Crescens Diane Tiu, Daniela Morales-Espinosa, Christa Raab, Bettina Rehbein, Gabriele Hintzen, Kerstin Pietzko, Paulien Ravenstijn, Michael Emig, Anthony B. El-Khoueiry
The AFM24 combination with atezolizumab study (NCT05109442) abstract details the trial design and rationale for the combination study of AFM24 and atezolizumab in patients with advanced EGFR-expressing solid tumors.
Anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors which enhance anti-tumor activity of a patient’s adaptive immunity, have already demonstrated efficacy as monotherapy and are playing an increasingly prominent role in cancer treatment. The combination of AFM24 and PD-L1 inhibitor, atezolizumab, may represent a promising new treatment modality, enhancing both the innate and adaptive immune responses to target EGFR+ tumor cells.
An ongoing phase 1/2a open-label, non-randomized, multicenter, dose escalation (phase 1) and dose expansion (phase 2) study was initiated in November 2021 to evaluate the safety, tolerability and efficacy of AFM24 in combination with atezolizumab. The primary aim of the phase 1 study is to determine the maximum tolerated dose and the RP2D of AFM24. Eligible patients must have advanced, histologically confirmed EGFR+ disease and confirmed disease progression after treatment with ≥1 prior therapy.
A standard 3+3 design will be used to determine the RP2D. Escalating doses of AFM24 will be given to each cohort as weekly intravenous (IV) infusions. The starting dose and at least two planned dose escalations are based on results from the ongoing AFM24 monotherapy trial. Atezolizumab is given at a fixed dose of 840 mg biweekly IV infusion. Patients will receive AFM24 and atezolizumab treatment until disease progression, intolerable toxicity, patient withdrawal, or termination of treatment at investigator’s discretion.
The phase 2a study will establish the overall response rate and safety of the 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 (PK), pharmacodynamics (PD), and immunogenicity.
Omar Saavedra Hadea, Eric Christenson, Anthony B. El-Khoueiry, Andreas Cervantes, Christa Raab, Ulrike Gartner, Kerstin Pietzko, Gabriele Hintzen, Paulien Ravenstijn, Daniela Morales-Espinosa, Juanita Suzanne Lopez
The AFM24 combination study with SNK01 autologous natural killer cells (NCT05099549) includes information about the dose-escalation and dose-expansion phase of AFM24 in combination with SNK01 autologous NK cells in patients with advanced EGFR+ solid tumors.
Autologous NK cell transfer represents a promising treatment strategy, with ex vivo expansion and activation enhancing the specificity and anti-tumor activity of NK cells. The efficacy of this approach may be enhanced through the addition of tumor-targeting antibodies, augmenting NK-cell mediated ADCC.
An ongoing phase 1/2a open-label, non-randomized, multicenter, dose escalation (phase 1) and dose expansion (phase 2) study were initiated in November 2021 to evaluate the safety, tolerability and efficacy of AFM24 in combination with SNK01 autologous NK cells in patients with advanced EGFR+ solid tumors.
The primary aim of the phase 1 study is to determine the maximum tolerated dose and RP2D of AFM24 in combination with SNK01 at a fixed dose of NK cells using a standard 3+3 design.
Eligible patients must have advanced or metastatic disease with positive immunohistochemical staining for EGFR in > 1% of tumor cells and be refractory to standard-of-care treatment.
AFM24 is administered at an escalating dose as weekly intravenous (IV) infusions; the starting dose (160 mg) and the dose escalations for each cohort are based on the results from the ongoing monotherapy trial. SNK01 NK cells are given at a fixed dose as a weekly IV infusion, concomitantly with AFM24.
Patients will receive the combination therapy until disease progression, intolerable toxicity, patient withdrawal, or termination of treatment at investigator’s discretion.
Phase 2 will establish the overall response rate of combination therapy in patients with treatment refractory, advanced or metastatic squamous cell carcinoma of the head and neck, non-small cell lung cancer, or colorectal cancer as the primary endpoint. Efficacy will also be measured by assessing progression-free and overall survival. Secondary endpoints for both phases include treatment-emergent adverse events, serious adverse events, pharmacokinetics and immunogenicity.
Anthony B. El-Khoueiry, Paul Y. Song, Jennifer Rubel, Dorna Y. Pourang, Christa Raab, Gabriele Hintzen, Michael Emig, Pilar Nava-Parada
More details about the program for the ASCO Annual Meeting are available online at www.asco.org
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.
Affimed is evaluating AFM24 in patients with advanced EGFR-expressing solid malignancies whose disease has progressed after treatment with previous anticancer therapies as monotherapy and in combinations with other cancer treatments. AFM24-101, a monotherapy, first-in-human phase 1/2a open-label, is a non-randomized, multi-center, multiple ascending dose escalation and expansion study. Additional details may be found at www.clinicaltrials.gov using the identifier NCT04259450. Furthermore, AFM24 is being evaluated in a phase 1/2a study in combination with Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab (AFM24-102, NCT05109442). Affimed and NKGen Biotech have initiated a phase 1/2a study (AFM24-103), investigating AFM24 in combination with SNK01, NKGen Biotech’s autologous NK cell product (NCT05099549).
About Affimed N.V.
Affimed (Nasdaq: AFMD) is a clinical-stage immuno-oncology company committed to give patients back their innate ability to fight cancer by actualizing the untapped potential of the innate immune system. The company’s proprietary ROCK® platform enables a tumor-targeted approach to recognize and kill a range of hematologic and solid tumors, enabling a broad pipeline of wholly-owned and partnered single agent and combination therapy programs. The ROCK® platform predictably generates customized innate cell engager (ICE®) molecules, which use patients’ immune cells to destroy tumor cells. This innovative approach enabled Affimed to become the first company with a clinical-stage ICE®. Headquartered in Heidelberg, Germany, with offices in New York, NY, Affimed is led by an experienced team of biotechnology and pharmaceutical leaders united by a bold vision to stop cancer from ever derailing patients’ lives. For more about the company’s people, pipeline and partners, please visit: www.affimed.com.
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