860MO MRG003: A novel EGFR-targeted antibody-drug conjugant (ADC) for recurrent/metastatic nasopharyngeal carcinoma

There is an unmet need for more effective treatments in recurrent/metastatic nasopharyngeal carcinoma (r/m NPC) after chemo- and immune-therapy. MRG003 is a novel ADC composed of a humanized anti-EGFR mAb conjugated to MMAE via a vc-linker. Here we report the primary dose finding study results of MRG003 in r/m NPC. This is a phase IIa study to evaluate the safety and efficacy of MRG003 in patients (pts) with pathologically documented r/m NPC, who had failed prior platinum and/or PD-(L)1 therapy. The study investigated two dose levels of MRG003 (2.0 or 2.3mg/kg, Q3W) to identify an optimal dose. The primary endpoint is objective response rate (ORR) per RECIST 1.1. Secondary endpoints include disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and safety. A total of 61 pts received at least 1 dose of MRG003, 30 pts at 2.0 mg/kg (DL1) and 31 pts at 2.3 mg/kg (DL2). Most pts (52/61) received ≥2 lines of prior treatment and 53 (86.9%) pts had prior platinum and PD-1/L1 therapy. By the cut-off date (March 15, 2023), 28 pts were evaluable in the DL1 cohort, the ORR and DCR were 39.3% and 71.4%, respectively. The ORR and DCR of 29 evaluable pts in the DL2 cohort were 55.2% and 86.2%, respectively. Median DoR (mDoR) was 6.8 months (95%CI: 5.7, 16.3) in DL1 and 6.8 months (95%CI: 2.9, 9.8) in DL2. The median PFS (mPFS) in DL1 cohort was 7.3 months (95%CI: 2.9, 9.7), while it was immature in DL2 cohorts. Most commonly reported treatment-related AEs (TRAEs) assessed by investigators were rash (49.2%), pruritus (41.0%), anemia (34.4%), and alopecia (31.1%); majority of TRAEs were grade 1 or 2 per CTCAE 5.0. The incidence of treatment related severe adverse event (SAE) was 11.5% (7/61). Dose reduction rate due to TRAEs were 13.1% (8/61) and 3 pts discontinued treatment (4.9%). No treatment related deaths were observed. MRG003 demonstrated promising antitumor activity in the late line r/m NPC patients, and with an acceptable tolerance and manageable safety profile. Based on numerically higher ORR and potentially better efficacy than 2.0 mg/kg group and well tolerated safety profile, 2.3mg/kg is the recommended dose for further pivotal study.