MRG002, a novel HER2-targeted antibody-drug conjugate (ADC), demonstrated promising efficacy and was well-tolerated in patients with HER2-low breast cancer, according to findings from a phase 2 study.

These findings were presented by lead author, Zefei Jiang, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, at the 2022 ASCO Annual Meeting.

“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,” wrote Dr Jiang and colleagues.

This phase 2 study aimed to examine the efficacy of MRG002 in patients with HER2-low breast cancer.

The primary study end point was objective response rate (ORR) assessed by independent review committee (IRC). Secondary end points included progression-free survival (PFS), disease control rate, and safety.

A total of 56 patients (median age, 55 years) were enrolled in the study as of the data cutoff date of December 31, 2021. MRG002 was administered intravenously once every 3 weeks at the dose of 2.6 mg/kg until disease progression or unacceptable toxicity. The majority of patients (83.9%) were HER2 IHC1+, 85.7% were hormone receptor (HR)-positive, and 57.1% had an ECOG performance status of 1.

Of the patients enrolled on the study, 28 (50%) patients received ≥2 lines of chemotherapy. The median number of prior treatments was 3. There were 41 (73.2%) patients with visceral metastases and 31 (55.4%) with bone metastases.

Among 49 evaluable patients, the ORR was 34.7% and disease control rate was 75.5%, with 17 patients experience a partial response, 20 patients experiencing stable disease, and 12 patients experiencing progressive disease.

Among patients with visceral metastases, subgroup analysis reveals the ORR was 39.5% and disease control rate was 76.3%. Tumor responses were similar in both the HER2 IHC 1+ and IHC 2+ subgroups (34.1% and 37.5%, respectively). Researchers noted that this may be attributed to fewer IHC 2+ enrollment in this trial.

Among patients with triple-negative breast cancer (n = 8), the ORR was 37.5% and disease control rate was 62.5%, demonstrating promising activity in these patients after ≥2 lines of therapy.

The most common treatment-related adverse events (AEs; ≥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%); and were all of grade 1 or 2. The most common grade ≥3 treatment-related AE (≥10%) was neutrophil count decreased (14.3%). There were no treatment-related deaths.

“MRG002 shows promising efficacy and well tolerated in patients with HER2-low breast cancer. Further evaluation is underway,” concluded Dr Jiang and colleagues.

Source:

Jiang Z, Sun T, Wang X, et al. 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. Presented at: ASCO Annual Meeting; June 3-7, 2022. Chicago, IL, and virtual. Abstract 1102.