A multiple center, open-label, single-arm, phase II clinical trial of MRG002, an HER2-targeted antibody-drug conjugate, in patients with HER2-low expressing advanced or metastatic breast cancer.

Abstract

1102 Background: MRG002 is a novel HER2-targeted ADC, composed of a sugar-modified trastuzumab, MMAE payload and a cleavable vc-linker. MRG002 was effective in HER2-low expressing breast cancer in preclinical studies. Hence, we conducted the phase II study to evaluate the safety and anti-tumor efficacy of MRG002 in HER-low breast cancer. Methods: HER2 low tumor expression was determined by a central lab and had to be immunohistochemistry (IHC)1+ or 2+/ISH-. Eligible patients had advanced/metastatic HER2-low expressing breast cancer that failed standard therapies. MRG002 was administered intravenously once every 3 weeks at the dose of 2.6 mg/kg, until disease progression or unacceptable toxicity which ever occurred first. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC). The secondary endpoints were progression-free survival (PFS), disease control rate (DCR), and safety. Results: A total of 56 female patients with HER2-low advanced or metastatic breast cancer were enrolled at the time of data cut-off (Dec 31, 2021) and had received at least one cycle of MRG002. The median age was 55 (30-72) years. Most patients were HER2 IHC1+ (83.9%), hormone receptor positive (HR+) (85.7%), and with a ECOG PS of 1 (57.1%). Twenty-eight patients (50.0%) had received at least 2 lines of chemotherapy and the median treatment was 3. Forty-one patients (73.2%) had visceral metastasis and 31 patients (55.4%) had bone metastasis. The ORR and DCR in 49 evaluable patients were 34.7% and 75.5%, with 17 PR, 20 SD and 12 PD. Subgroup analysis indicated that the ORR was 39.5% (15/38) and DCR was 76.3% (29/38) among the evaluable patients with visceral metastasis. The tumor responses were similar in both the HER2 IHC 1+ and IHC 2+ subgroups, as is 34.1% and 37.5% respectively, which might be attributed to fewer IHC 2+ enrollment in this trial. Although only 8 HR- subjects enrolled in our study, the ORR (37.5%) and DCR (62.5%) is promising in these triple negative BC patients post to ≥2 line therapies. Most common treatment related adverse events (TRAEs) were grade 1 or 2. The most common TRAEs (≥20%) were neutrophil count decreased (53.6%), white blood cell count decreased (48.2%), AST increased (46.4%), alopecia and ALT increased (39.3%), blood lactate dehydrogenase increased(33.9%), GGT increased (32.1%), nausea (32.1%), vomiting (23.2%), constipation (23.2%), diarrhea(23.2%) and hyperglycemia (21.4%). Most common grade ≥3 TRAE(≥10%) was neutrophil count decreased(14.3%). No patients died due to MRG002. Conclusions: MRG002 shows promising efficacyand well tolerated in patients with HER2-low breast cancer. Further evaluation is underway. Clinical trial information: NCT04742153.