MEDI5752 Shows Safety and Clinical Activity in Advanced RCC

MEDI5752 is a bispecific monoclonal antibody that targets programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The results of phase I, open-label clinical trial (NCT03530397) evaluating the efficacy of MEDI5752 monotherapy administered intravenously every three weeks at doses ranging from 2.25 to 2500 mg demonstrated promising antineoplastic effects in patients with advanced solid tumors. The maximum tolerated dose was not attained. Doses <1500 mg were better tolerated than doses equal to or greater than the study’s primary findings are being presented regarding patients diagnosed with advanced renal cell carcinoma in the escalation and expansion (EXP) cohorts. Patients who met the eligibility criteria were those who were 18 or older and had an Eastern Cooperative Oncology Group Performstudy’s primary aim cases of ESC and EXP.

Patients who qualified for the study had a clear cell component renal cell carcinoma (ccRCC), had not received immunotherapy treatment before (IO-naïve), and had received a maximum of two prior lines of therapy. The patients were managed until disease progression or intolerable adverse effects. The primary goals were to ensure safety and tolerability (ESC) while evaluating antitumor activity through objective response according to RECIST v1.1. A total of 46 patients diagnosed with renal cell carcinoma were treated, comprising 19 cases of early-stage cancer and 27 cases of advanced-stage cancer. During the ESC study, patients (all of whom were IO-naïve and had clear cell histology, with 73.7% having undergone prior nephrectomy and 26.3% receiving first-line treatment) were administered bispecific monoclonal antibodies that were: 750 mg (n=1), 2000 mg (n=16), and 2500 mg (n=2). Seven patients (36.8%) exhibited objective responses, all partial responses (PRs). Among these, four were first-line (1L) treatments, with one each having papillary and sarcomatoid histology. In the clinical trial, patients (all with no prior exposure to IO treatment, 63.0% with a history of nephrectomy, 48.1% receiving first-line treatment [of whom 69.2% had intermediate/poor risk according to the International Metastatic Renal Cell Carcinoma Database Consortium criteria], and 96.3% with clear cell histology) were administered MEDI5752 intravenously at a dosage of 1500 mg every three weeks.

Out of the total number of participants, ten individuals (38.5%) exhibited objective responses, which included two complete responses (CRs) and eight partial responses (PRs). Among the patients with 1L EXP, 58.3% exhibited objective responses, which included one complete response and six partial responses. The disease control rate (DCR) was found to be 91.7%. Grade 3/4 treatment-related adverse events (TRAEs) were observed in 68.4% of patients receiving the experimental standard care (ESC) and 74.1% of patients receiving the experimental treatment (EXP). In the EXP study, treatment-emergent adverse events (TEAEs), notably hepatotoxicity, were the primary reason for treatment discontinuation. At a median follow-up duration of 14.6 months, the median time of response (DOR) – which also includes those who discontinued MEDI5752 due to adverse events – as well as the median progression-free survival (PFS) and overall survival (OS) were not reached in first-line experimental patients. The MEDI5752 monotherapy exhibited profound and persistent antineoplastic efficacy in patients with advanced renal cell carcinoma, notwithstanding the elevated rates of treatment discontinuation, particularly in the first-line setting. To more accurately delineate the risk-benefit ratio, the administration of MEDI5752 is currently under investigation at dosages <1500 mg in expansion cohorts for 1L ccRCC.

Source: https://meetings.asco.org/abstracts-presentations/209273

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03530397

Laurence Albiges, Laura Medina Rodriguez, Sang-We Kim, Seock-Ah Im, Enric Carcereny, Sun Young Rha, Ben Tran, Julio Oliveira, Pablo Maroto-Rey, Wu-Chou Su, Mark Voskoboynik, Alejo Rodriguez-Vida, Luis Costa, Paolo Antonio Ascierto, Maria Amelia Insa Molla, Yi Wang, Shelby D. Gainer, Deepa S Subramaniam, Martin H Voss/Safety and clinical activity of MEDI5752, a PD-1/CTLA-4 bispecific checkpoint inhibitor, as monotherapy in patients (pts) with advanced renal cell carcinoma (RCC): Preliminary results from an FTIH trial/J Clin Oncol 40, 2022 (suppl 16; abstr 107) DOI10.1200/JCO.2022.40.16_suppl.107