At ESMO 2024, updates were presented on davutamig, a novel human bispecific antibody targeting MET alterations in advanced NSCLC. This first-in-human study aimed to assess the safety, tolerability, and antitumor activity of davutamig in patients with unresectable or metastatic NSCLC who had limited standard treatment options.

The study included a dose-escalation phase with davutamig administered intravenously at doses of 500, 1000, and 2000 mg every three weeks. Following this, a cohort expansion phase at the 2000 mg dose was conducted, focusing on patients with confirmed MET alterations, including exon 14 skipping mutations, gene amplification, and protein overexpression. Tumor assessments were performed every six weeks until disease progression or study completion.

As of December 8, 2023, 82 patients (median age 67 years; 44% female; 71% Asian; 37% with EGFR mutation) were enrolled. The majority (61%) had received prior anti–PD-(L)1 therapy, with a median of 2 prior lines of therapy. Patients received a median of 4 doses of davutamig (range 1–42).

Davutamig demonstrated a generally favorable safety profile. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 29% (24/82) of patients, with treatment-related grade ≥3 TEAEs in 6% (5/82). TEAEs led to treatment discontinuation in 4% of patients (3/82), including one case of pneumonitis with a fatal outcome. Peripheral edema was reported in 13% (11/82) of patients, with grade ≥3 edema in 1 patient.

Among the 74 patients who received the 2000 mg dose, 9 patients (12%) had a partial response, and 43 patients (58%) demonstrated disease control. The median duration of response was 7.4 months. Objective response rates (ORR) for MET TKI-naive patients with centrally confirmed MET alterations were 25% (4/16) for MET exon 14 mutations and 13% (4/32) for MET overexpression and/or amplification without MET exon 14 alteration. No responses were observed in patients with MET exon 14 mutations who had prior MET TKI treatment.

Conclusion 

Davutamig has shown potential in targeting MET alterations in advanced NSCLC. Its dual-targeting mechanism disrupts MET signaling, which may offer benefits to patients with limited treatment options. The preliminary data from this study suggest that davutamig could contribute to the evolving treatment landscape for NSCLC, emphasizing the ongoing development of personalized approaches in oncology.