AFM24/Atezolizumab Earns FDA Fast Track Status in EGFR Wild-Type NSCLC

AFM is designed as a tetravalent, bispecific ICE agent that binds to CD16A on innate immune cells and EGFR to activate the innate immune system, thereby destroying cancer cells.

The FDA has granted fast track designation to AFM24, a novel innate cell engager (ICE) therapy, in combination with atezolizumab (Tecentriq) for patients with advanced and/or metastatic EGFR wild-type non–small cell lung cancer (NSCLC) that has progressed following prior anti–PD-L1 treatment and platinum-containing chemotherapy, according to a press release from the developers, Affimed N.V.¹

AFM is designed as a tetravalent, bispecific ICE agent that binds to CD16A on innate immune cells and EGFR to activate the innate immune system, thereby destroying cancer cells. Specifically, the agent makes use of EGFR to facilitate antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis when targeting cancer cells.

“The fast track designation emphasizes the belief in the potential of this combination therapy to address currently unmet needs of patients with this devastating, life-threatening disease who have exhausted all standard-of-care options, including chemotherapy and checkpoint inhibitors,” Wolfgang Fischer, PhD, chief operating officer at Affimed, said in the press release.¹

Supporting data for the fast track designation came from the phase 1/2a AFM24-102 trial (NCT05109442), which is evaluating AFM24 plus atezolizumab in patients with advanced or metastatic solid malignancies expressing EGFR.

With a data cutoff of March 18, 2024, 1 of 15 evaluable patients with EGFR wild-type NSCLC had a confirmed complete response (CR) following treatment with AFM24/atezolizumab.² Additionally, investigators reported partial responses (PRs) in 3 patients and stable disease in 7. The disease control rate (DCR) with the combination was 73.3% (n = 11/15). Data also showed a median progression-free survival (PFS) of 5.9 months.

The experimental combination appeared to be tolerable among this cohort of heavily pretreated patients. Common adverse effects (AEs) included mild to moderate infusion-related reactions as well as transient mild to moderate liver enzyme increases. Overall, the safety profile of the study treatment was comparable with previous reports of each individual agent.

Investigators will present the full dataset from the AFM24-102 trial at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Additionally, the EGFR wild-type NSCLC cohort is planned to include a maximum of 40 patients, and investigators look to include up to 25 of those with EGFR-mutated disease.

“We are very encouraged to see objective and lasting responses in patients who have [progressed on] multiple lines of therapy including platinum doublets and checkpoint inhibitors,” Andreas Harstrick, MD, chief medical officer and acting chief executive officer at Affimed, said in a press release on these data.² “These data support our hypothesis that the combination of AFM24 and PD-1 targeting may act synergistically on the immunity cycle. It is remarkable that this can be achieved with a chemotherapy-free approach. We are committed to continuing clinical development of this therapy and are enrolling additional patients for both [EGFR wild-type] and [EGFR-mutant] NSCLC.”

In the open-label, multicenter AFM24-102 trial, patients received AFM24 plus atezolizumab intravenously as part of a traditional 3+3 escalation phase and a dose-expansion phase.³ Investigators administered atezolizumab at 840 mg in 14 mL injections.

The trial’s primary end points included dose-limiting toxicities in phase 1 and objective response rate in phase 2. Secondary end points included PFS, duration of response, DCR, clinical benefit rate, and pharmacokinetics.

Patients 18 years and older with histologically or cytologically confirmed advanced or metastatic EGFR-positive selected cancer types or advanced or metastatic EGFR wild-type NSCLC that has progressed following 1 or more prior lines of therapy were eligible for enrollment on the trial. Other eligibility criteria included having adequate organ function and measurable disease per RECIST v1.1 guidelines.

References

1. Affimed receives fast track designation for combination therapy of AFM24 with atezolizumab for EGFR wild-type non-small cell lung cancer. News release. Affimed N.V. May 29, 2024. Accessed May 29, 2024. https://tinyurl.com/5j4367y8
2. Affimed announces positive early efficacy and progression free survival results of AFM24-102 study in EGFR wild-type non-small cell lung cancer at the Annual Meeting of the American Society of Clinical Oncology 2024. News release. Affimed N.V. May 23, 2024. Accessed May 29, 2024. https://tinyurl.com/yc8x7w77
3. Study to assess AFM24 in combination with atezolizumab in selected advanced/​metastatic EGFR-expressing cancers. ClinicalTrials.gov. Accessed May 29, 2024. https://tinyurl.com/ykhmwnm4