AFM24 Plus Atezolizumab Wins FDA Fast Track Designation for EGFR Wild-Type NSCLC

FDA

The FDA has granted fast track designation to the innate cell engager (ICE) AFM24 in combination with atezolizumab (Tecentriq) for the treatment of patients with advanced and/or metastatic non–small cell lung cancer (NSCLC) not harboring activating EGFR mutations after progression on PD-1/PD-L1 therapy and platinum-based chemotherapy.¹

The designation is supported by initial efficacy data from the EGFR wild-type cohort of the phase 1/2a AFM24-102 trial (NCT05109442). Previously reported data showed that among 15 patients with EGFR wild-type NSCLC, 4 achieved responses, including 1 patient who had a confirmed complete response, 2 patients who had a confirmed partial response (PR), and 1 patient who had an unconfirmed PR. Patients in the EGFR wild-type cohort had received a median of 2 prior lines of therapy, and all had experienced disease progression on PD-1/PD-L1 therapy.²

Additional data from the EGFR wild-type cohort will be presented at the 2024 ASCO Annual Meeting.¹

“The clinical data of AFM24 in combination with the checkpoint inhibitor atezolizumab is compelling. We’re observing meaningful responses in patients resistant to prior checkpoint inhibitor treatment,” Wolfgang Fischer, PhD, chief operating officer of Affimed N.V., stated in a news release. “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.”

AFM24 is a tetravalent, bispecific ICE designed to activate the innate immune system by binding to CD16A on innate immune cells and EGFR.

AFM24-102 is an open-label, nonrandomized, multicenter, dose-escalation and -expansion trial evaluating AFM24 plus atezolizumab in patients with selected EGFR-expressing advanced solid malignancies who experienced disease progression after prior treatment.³

To enroll, patients need to be at least 18 years of age with histologically or cytologically confirmed advanced or metastatic, EGFR-positive selected cancer types. All patients must have adequate organ function. In phase 1, patients are required to have evaluable or measurable disease per RECIST 1.1 criteria, and in phase 2, measurable disease per RECIST 1.1 criteria is required.

For the EGFR wild-type NSCLC cohort, patients need to have experienced disease progression after at least 1 prior line of therapy that included platinum-based doublet chemotherapy. Previous treatment with a PD-1 or PD-L1 inhibitor is required either in combination with chemotherapy, or before or after chemotherapy.

The trial also includes cohorts for patients with advanced, unresectable, or metastatic gastric/gastroesophageal junction cancer, advanced or metastatic hepatocellular carcinoma, and advanced or metastatic NSCLC harboring a targetable EGFR mutation.

Key exclusion criteria for all patients include treatment with systemic anticancer therapy, including investigational agents, within 4 weeks of the first dose of study drug; radiation therapy within 2 weeks before first dose of study drug; and current, active participation in another clinical trial or treatment within another investigational agent.

The dose-escalation portion of the study is utilizing a traditional 3+3 design to evaluate AFM24 at varying doses in combination with 840 mg of intravenous atezolizumab to determine the maximum tolerated dose and recommended phase 2 dose of AFM24. In dose escalation, patients will receive AFM24 plus 840 mg of intravenous atezolizumab to evaluate the preliminary efficacy of the combination and further examine its safety.

The primary end points of the study are focused on evaluating the incidence of dose-limiting toxicities (phase 1) and overall response rate (ORR; phase 2a). Secondary end points include safety, pharmacokinetics, and efficacy consisting of ORR (phase 1), progression-free survival (phase 2a), duration of response (phase 2a), clinical benefit rate (phase 2a), and disease control rate (phase 2a).

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. May 29, 2024. Accessed May 29, 2024. https://www.affimed.com/affimed-receives-fast-track-designation-for-combination-therapy-of-afm24-with-atezolizumab-for-egfr-wild-type-non-small-cell-lung-cancer/
2. Affimed provides clinical response update on AFM24-102 trial in EGFR-wildtype non-small cell lung cancer. News release. Affimed. January 8, 2024. Accessed May 29, 2024. https://www.affimed.com/affimed-provides-clinical-response-update-on-afm24-102-trial-in-egfr-wildtype-non-small-cell-lung-cancer/
3. Study to assess AFM24 in combination with atezolizumab in selected advanced/​metastatic EGFR-expressing cancers. ClinicalTrials.gov. Updated August 29, 2023. Accessed May 29, 2024. https://clinicaltrials.gov/study/NCT05109442