(UroToday.com) At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the poster session focused on Kidney and Bladder cancers on Saturday afternoon included a presentation from Dr. Wang Qu examining the HER2-targeted antibody-drug conjugate (ADC) MRG002 in patients with metastatic urothelial carcinoma (UC).
In general, patients with advanced UC have a poor prognosis. However, overexpression of HER-2 is associated with particularly poor outcomes. Among these patients, targeted therapy with an anti-HER-2 antibody-drug conjugate (ADC) has shown promising efficacy.
As reported in this abstract, the authors performed a single-arm, multicenter phase II study (MRG002-006) to assess the efficacy and safety of the HER2-targeted ADC MRG002 in patients with HER2 positive UC (NCT04839510). They included patients with histologically HER2-positive (IHC 2+ or 3+) UC confirmed by a central-laboratory review who had ECOG performance status of 0 or 1 and had previously received at least one line of standard treatment. The targeted enrollment was approximately 40 patients including an initial dose finding stage (in which patients were assigned to receive MRG002 at a dose of 2.6 mg/kg or 2.2 mg/kg administered by intravenous infusion every 3 weeks) and a subsequent dose expansion stage.
The primary study endpoint was objective response rate (ORR) per RECIST 1.1 with secondary endpoints including safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
As of the data cutoff of December 31, 2021, 39 patients were enrolled with enrollment continuing. At baseline, 80% pts (28/35) had visceral metastasis and most (28/35) received two or more lines of treatment including immune checkpoint inhibitor (ICI) therapy.in the majority (n=29; 83%).
During the initial dose finding stage, 9 patients were treated at 2.6 mg/kg and 26 patients were dosed at 2.2 mg/kg. Based on safety analysis, 2.2 mg/kg was adopted as the recommended dosage for the expansion phase.
By the cut-off date, 23 patients were evaluable and, among these, the ORR was 65% (15/23, 95% CI: 44.9%–81.2%), with 9% CR. One of the patients with complete response had a response duration of more than 9.5 months. The DCR was 91% (21/23, 95% CI: 73.2%–97.6%). The estimated median PFS among evaluable patients was 5.5 months (95% CI: 2.7–NR).
Subgroup analysis indicated that the ORR was 65% among those patients who had received two or more lines of treatment (n=17) and 78% among those who had received both platinum-containing chemotherapy and ICI treatment (n=18).
The most common treatment-related AEs were anemia (34%), alopecia (34%), AST increased (31%), neutrophil count decreased (26%), neuropathy peripheral (23%), constipation (17%), decreased appetite (17%); most were grade 1 or 2 per CTCAE 5.0. The incidence of SAE was 17% (6/35). At the dose of 2.6mg/kg, 1 patient discontinued the treatment due to hypotension and 1 patient experienced ileus, which was considered caused by neurotoxicity of MRG002. There were no similar events among the patients who were treated at the dose of 2.2mg/kg.
Thus, Dr. Qu concluded that these preliminary results examining the ADC MRG002 demonstrated a clinically meaningful response among patients with HER-2 positive unresectable locally advanced or metastatic UC who have progressed on prior treatments, especially in those progressed after platinum-containing chemotherapy and ICI therapy.
Presented by: Wang Qu, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China