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

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

NCT05126719.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Miracogen Inc.

Funding

Shanghai Miracogen Inc.

Disclosure

All authors have declared no conflicts of interest.