No abstract

T-cell engagers (TCE) are a rapidly evolving novel group of treatments that have in common the concurrent engagement of a T-cell surface molecule and a tumoral cell antigen. Bispecific antibodies and genetically engineered adoptive cell therapies, as chimeric antigen receptors or T-cell receptors, have similarities and differences among their mechanisms of action, toxicity profiles, and resistance pathways. Nevertheless, the success observed in the hematologic field has not been obtained with solid tumors yet, as they are biologically more complex and have few truly tumor-specific cell surface antigens that can be targeted with high avidity T cells. Different strategies are under study to improve their short-term perspective, such as new generations of more active TCEs, multi-target or combination of different treatments approaches, or to improve the manufacturing processes. A comprehensive review of TCEs as a grouped treatment class, their current status, and research directions in their application to solid tumors therapeutics are discussed here.

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

e15229 Background: HPD is a new pattern of response consisting of accelerated tumor growth due to immunotherapy (5%-20% of pts on IO drugs). The tumor growth rate (TGR, Champiat et al.) estimates the differential increase in tumor volume over time, pre- and on IO drugs, to assess for HPD, but it is not easily calculated in practice. A comparison of the different methods to identify HPD is missing. Methods: Retrospective study of 182 consecutive pts treated in Phase 1 studies of IO drugs at START Madrid-CIOCC in 2017-8, comparing 3 HPD measurement criteria (Champiat, Matos -which does not use pre-baseline CT scans-, and Saâda-Bouzid). Cohen’s Kappa index was calculated as a measure of the agreement between the 3 methods, being those values closer to 1 the more concordant ones. Overall survival (OS) rates were calculated by Kaplan-Meier (p < 0.05 to be significant). Results: 99 (54%) of 182 pts had progressive disease at cycle 1 of treatment and in 62 (34%) pre-baseline CT scans were available to calculate TGR. The Champiat method identified 18 (9.9%) pts with HPD. Of 61 cases validated to comparison, the Matos criteria labeled 27 pts (14.8% of 182) with HPD, of whom only 10 pts coincided with those identified by Champiat with a low agreement (Kappa: 0.140, p:0.251). No significant differences in OS between pts with non-HPD vs HPD by Matos criteria were seen (p = 0.16). With Saâda-Bouzid method, of 59 cases validated to comparison, 17 pts (9.3% of 182) were labeled with HPD and 13 of them coincided with those identified by Champiat method with a high agreement (Kappa:0.706, p:0.000). Differences in OS between non-HPD vs HPD pts were statistically significant (p = 0.038). Conclusions: HPD might have a detrimental effect to 10% of pts on IO drugs, also in our series. Every effort should be done to obtain pre-baseline CT scans to identify HPD response to IO drugs, based on differential TGR. The use of Saâda-Bouzid method is preferred due to its practical application and its correlation with survival. [Table: see text]