Although no patient had an objective response, 2 MBC patients with SD experienced prolonged PFS and there appeared to be a relationship between dose level and clinical response
Although no patient had an objective response, 2 MBC patients with SD experienced prolonged PFS and there appeared to be a relationship between dose level and clinical response. mg/kg on Weeks 1, 2, 4, and 5; C) 100 mg once weekly; D)100 mg Q2W. mCRPC patients were enrolled in Cohorts A and B; MBC patients were enrolled in all cohorts. Efficacy was assessed by RECIST and Prostate Cancer Clinical Trials Working Group 2 criteria. Results: Thirty-four patients (22 MBC; 12 mCRPC) received 1 dose of LY3022855. At Day 8, circulating CSF-1 levels increased and pro-inflammatory monocytes CD14DIMCD16BRIGHT decreased. Best RECIST response was stable disease in five MBC patients (23%; duration 82C302 days) and three SVT-40776 (Tarafenacin) mCRPC patients (25%; duration 50C124 days). Two MBC patients (Cohort A) had durable stable disease 9 months and a third MBC patient had palpable reduction in a nontarget neck mass. Immune-related gene activation in tumor biopsies post-treatment was observed. Common any grade treatment-related adverse events were fatigue, decreased appetite, nausea, asymptomatic increased lipase, and creatine phosphokinase. Conclusions: LY3022855 was well tolerated and showed evidence of immune modulation. Clinically meaningful stable disease 9 months was observed in two MBC patients. = 12) and genes with low variance (variance p 200, = 29) were removed SVT-40776 (Tarafenacin) from further analysis. The resulting genes (= 689) were subjected to one-way ANOVA differential gene expression analysis (OmicSoft Array Studio 10.0.1.118; QIAGEN?, Cary, NC). Volcano plots were constructed (Tibco Spotfire Analyst 7.11.1; Tibco, Palo Alto, CA) and differentially-expressed genes were visualized via heatmap using ComplexHeatmap (21). Statistical Analyses To NCAM1 study the impact of LY3022855 on SVT-40776 (Tarafenacin) immune cell subsets and serum cytokines, the changes from baseline were summarized. For change from baseline analyses, baseline value was defined as the last reported measure on or before the first dose of LY3022855 (prior to the dose administration). For a change from baseline within a cycle, baseline value was defined as the measure prior to the first dose of that cycle, unless otherwise specified. The safety population included patients who received 1 dose of LY3022855. The evaluable population included patients who completed one cycle of LY3022855 treatment, one baseline tumor biopsy, one post-treatment tumor biopsy, and one cycle of immune blood studies. Descriptive statistics were used to summarize baseline patient characteristics, safety, and tumor response. The objective response rate (ORR) was estimated by the proportion of enrolled patients who had a best overall response (BOR) of complete response (CR), or partial response (PR). Disease control rate (DCR) was estimated by the proportion of enrolled patients who had a BOR of CR, PR, or stable disease (SD). Results Patients Twenty-two MBC patients were enrolled and all MBC patients received 1 dose of LY3022855(Figure 1A). In the MBC group, most patients (Cohort A, 83.3%; Cohort B, 40%; Cohort C, 100%; Cohort D, 83.3%) discontinued treatment due to progressive disease; 1 (16.7%) patient in Cohort A discontinued due to adverse event, 3 (60%) patients in Cohort B discontinued due to withdrawal by subject, and 1 (16.7%) patient in Cohort D died due to disease complication. Twelve mCRPC patients were enrolled, and all 12 received 1 dose of LY3022855 (Figure 1B). In the mCRPC group, most patients (Cohort A, 62.5%; Cohort B, 100%) discontinued treatment due to progressive disease; 2 (25.0%) patients in Cohort A discontinued due to physician decision, and 1 (12.5%) patient in Cohort B discontinued due to other reasons. Open in a separate window Open in a separate window Figure 1. Treatment duration and response for MBC (A) and mCRPC (B) patients in study (= 34). Each horizontal bar represents a patient. Response is per RECIST 1.1 criteria. Best overall response was SD (MBC, = 5; mCRPC, = 3) and PD (MBC, = 16; mCRPC, = 4). One MBC patient and five mCRPC patients were not evaluable (NE). MBC tumors were estrogen receptor (ER) and/or progesterone receptor (PR) positive; one patient had triple negative breast cancer (TNBC). Abbreviations: BOR, best overall response; HER2, human epidermal growth factor receptor 2; N, total number of patients; n, number of patients in the specified category; PD, progressive disease; Q2W, every two weeks; QW, weekly; WK1245, weeks.