Background: Ezabenlimab is a PD-1-targeting monoclonal antibody. Ezabenlimab is being investigated as monotherapy and in combination with other anti-cancer agents, and has been administered to >600 pts in combination settings. Here, we report results in pts who received 240 mg ezabenlimab monotherapy every 3 weeks (q3w).Methods: Data from two phase I dose escalation/expansion trials and a phase I imaging trial are presented. Dose escalation cohorts enrolled pts with any advanced solid tumours. Dose expansion included pts with: select advanced solid tumours (including NSCLC, bladder, melanoma, gastric, ovarian, triple-negative breast cancer and RCC); TMB-high tumours (excluding MSI-high); squamous cell cervical/anal/skin tumours and vaginal or vulvar squamous cell carcinoma. Prior anti-PD-1 therapy was permitted in dose escalation but not in expansion cohorts. Tumour response was evaluated as per RECIST 1.1. Safety was assessed by incidence and severity of adverse events (AEs).Results: 111 pts received ezabenlimab 240 mg q3w. 83 pts (75%) were female; median age, 62 yrs. At data cut-off (Nov 2020), 13 pts remain on treatment. Best overall confirmed response is shown in the table. Duration of response ranged from 43 to 570 days (response was ongoing in 9/16 pts at data cut-off). The most common AEs (all/G3) were fatigue (38.7%/3.6%), nausea (28.8%/0) and anaemia (21.6%/10.8%). The most common drug-related AE (all/G3) was fatigue (18.0%/0). 33 pts (29.7%) had immune-related AEs, most commonly hypothyroidism (7 pts [6.3%]). 38 pts (34.2%) had serious AEs (2 were considered treatment-related [G2 pyrexia and G3 rash]). There were no AEs leading to death. 2 pts had AEs leading to discontinuation (G2 colitis and G3 musculoskeletal pain). Anti-drug antibodies occurred infrequently and did not affect the PK profile of ezabenlimab.Conclusions: Ezabenlimab monotherapy showed anti-tumour activity similar to other checkpoint inhibitors and was well tolerated.
Glioblastoma (GBM) is the most common brain cancer. Resistance to front-line systemic therapy with temozolomide (TMZ) is correlated with O6-methylguanine-DNA-methyltransferase (MGMT) expression. Second-line treatment with bevacizumab has not improved overall survival. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent that has MGMT-independent cell-kill activity against GBM cell-lines and cancer stem cells in vitro. VAL-083 crosses the blood-brain barrier and showed promise against CNS tumors in prior NCI-sponsored clinical trials. The goal of this clinical trial is to determine appropriate VAL-083 dosing for advancement to Phase III trials as a new treatment for recurrent GBM. METHODS: Patients must have recurrent GBM following surgery, radiation, TMZ and bevacizumab. Phase I: Open-label, single-arm, dose-escalation study. Patients received VAL-083 on days 1,2,3 of a 21-day cycle, until reaching MTD. Phase II: Additional patients enrolled at MTD to further assess safety and outcomes. RESULTS: Phase I: 29 patients were enrolled across 9 dose cohorts (1.5-50 mg/m2/d). 40mg/m2/d was confirmed as MTD. Myelosuppression was mild; no drug-related serious adverse events were reported at doses up to 40mg/m2/d. Dose limiting G4 thrombocytopenia was observed at higher doses. Platelet nadir occurred around day 20 and resolved rapidly and spontaneously. A dose-related survival improvement was observed. Pharmacokinetic analyses show 1-2h plasma terminal half-life; average Cmax 781ng/mL at 40mg/m2/d. Phase II: 14 patients were enrolled at 40mg/m2/d. To date, safety observations in Phase II are consistent with Phase I. CONCLUSIONS: VAL-083 at 40mg/m2/d exhibits a favorable safety profile and dose-related trend toward clinically meaningful improved survival in refractory GBM patient
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