AFM24 Plus Atezolizumab Shows Acceptable Safety, Early Activity in EGFR+ Solid Tumors

A doublet comprised of the bispecific innate cell engager (ICE), AFM24, and atezolizumab (Tecentriq) had a tolerable safety profile and elicited responses in patients with advanced EGFR-expressing solid tumors, according to data from a phase 1 trial (NCT05109442).

Data presented at the 2022 SITC Annual Meeting demonstrated that of the 3 patients evaluated in cohort 1 of the study, 1 patient with gastric cancer achieved a partial response following 2 cycles of the combination. Moreover, 1 patient with pancreatic adenocarcinoma achieved stable disease after 2 cycles of treatment.

“AFM24 [given] at 160 mg in combination with atezolizumab demonstrated a well-managed safety profile,” lead study author Omar Saavedra, MD, of Vall d’Hebron Institute of Oncology, in Barcelona, Spain, and colleagues, wrote in a poster on the data. “No dose-limiting toxicities [DLTs] were reported.”

AFM24 is an ICE that binds to EGFR on solid tumor cells as well as CD16A on natural killer (NK) cells or macrophages; this leads to redirection and activation of those cells and strengthens antitumor antibody-dependent cellular cytotoxicity and phagocytosis, respectively.

Data from prior studies have shown that AFM24 can elicit NK-mediated cytotoxicity of EGFR and have a manageable toxicity profile. Investigators hypothesized that pairing AFM24 with the PD-L1 inhibitor atezolizumab would leverage the crosstalk between the innate and adaptive immune responses to synergistically boost activity and improve outcomes in those with solid tumors that express EGFR.

To test this theory, the open-label, non-randomized, multicenter, dose-escalation study was launched. To be eligible for enrollment, patients needed to be 18 years of age or older, with a diagnosis of a solid tumor, confirmed EGFR expression on 1% or more of cancer cells, and an ECOG performance status of 0 or 1. Additionally, they must have progressed on all standard-of-care therapies and had evaluable or measurable disease per RECIST v1.1 criteria.

The dose-escalation phase of the trial included up to 18 patients who received an infusion of AFM24 at 160 mg at the beginning of week 4; this was followed by 160 mg of AFM24 and an 840-mg infusion of atezolizumab at the start of week 5. This treatment schedule continued until the beginning of week 12.

“The dose-escalation stage is adapted from a standard 3+3 design and the study will continue with AFM24 at a dose of 480 mg (the recommended phase 2 dose [RP2D] from the AFM24-101 monotherapy study),” the study authors noted.

The dose-expansion stage of the trial includes 3 cohorts. Cohort 1 will be comprised of 40 patients with wild type EGFR-positive non­–small cell lung cancer (NSCLC). Cohort 2 will include 40 patients with gastric or gastroesophageal junction (GEJ) adenocarcinomas. Finally, cohort 3 will include 25 patients with hepatocellular, hepatobiliary, or pancreatic adenocarcinomas.

The key objective of the study was to establish a RP2D or maximum tolerated dose of AFM24, as well as to understand the safety and tolerability of combination regimen.

As of June 7, 2022, a total of 4 patients had been enrolled to the trial. The mean age of these patients was 60 years (range, 50-73) and all were female. Three patients had an ECOG performance status of 0, and the last patient had a status of 1. All patients were Caucasian, Moreover, the median number of prior lines of therapy received was 3.5 (range, 3-4). One patient had gastric cancer and 3 patients had pancreatic adenocarcinoma.

Three of the 4 patients completed the safety lead-in phase with AFM24 given at 160 mg. However, following a grade 2 infusion-related reaction, 1 patient withdrew from the study. Moreover, 2 serious adverse effects (AEs) were reported in this phase; one was a grade 1 medication error that did not have a deleterious effect on the patient, and the other was a grade 2 infusion-related reaction (IRR) that called for extended hospitalization.

IRRs were experienced by 2 patients on the trial; they were observed during the first infusion of AFM24 and were found to be manageable with antihistamines.

Treatment-emergent AEs (TEAEs) that were grade 1 or 2 in severity were experienced by 33 patients; 2 patients had grade 3 TEAEs. The most common TEAEs experienced with the regimen were lymphocytopenia (n = 16), anemia (n = 4), neutropenia (n = 4), IRRs (n = 3), thrombocytopenia (n = 2), cough (n = 1), dyspnea (n = 1), vomiting (n = 1), fever (n = 1), asthenia (n = 1), ascites (n = 1), or a medication error (n = 1).

Notably, no grade 3 or 4 skin toxicities were experienced, and no on-study deaths occurred.

“The study is ongoing and dose escalation is proceeding at a dose of 480 mg AFM24,”study authors concluded.

Reference

Saavedra O, Morales-Espinosa D, Lopez J, et al. AFM24 and atezolizumab combination in patients with advanced epidermal growth factor receptor-expressing (EGFR+) solid tumors: Initial results from the phase 1 dose-escalation study. Journal for ImmunoTherapy of Cancer. 2022;10(suppl 2). doi:10.1136/jitc-2022-SITC2022.0746