Background: An increasing percentage of pancreatic cancer (PC) patients are looking for 3L+ options. As patient outcomes are improving with advances in treatment for PC, more patients need 3L+ treatments. Few trials focus on this patient segment as evaluation of drug effects can be complicated by comorbidity rates and disease-related SAEs. Having exhausted SOC chemotherapy backbones, patients increasingly search for novel therapies and clinical trial options. This assessment was to evaluate 3L+ PC trials for 1) sufficient patient interest, 2) a clinically evaluable patient population, and 3) guidelines/restrictions that could improve clinical assessment. Methods: Initiated as a retrospective evaluation of consenting patients screened for a prospective 2L+ pancreatic cancer Phase II trial with SM-88. A comparison of recurrent PC trials was performed by Novella to assess industry wide enrollment characteristics. Results: 32% of patients searching for clinical trials YTD 2018 in PanCAN’s database were looking for 3L+ treatments, up from 25% in 2016. In the sample trial, rate of consents (n=72) increased hyperbolically, reaching ~1/pt/day by end of analysis (24 sites). Inc/exc criteria were broadly standard for sponsor-initiated trials, however ECOG PS 2 were eligible. 38% screen failed, with hepatic labs (esp Alb & ALP) as most common reason. Industry analysis indicated expected 0.35 p/s/m for refractory PC trials and 20% screen fail. 93% (37/40) of SAEs were unrelated to study drug, including 11 G4 or G5 prior to receiving drug. Preliminary safety and efficacy results for the trial are reported elsewhere. Conclusions: Rapid enrollment from 3L+ patients demonstrated significant interest among this patient segment. The screen failure rate was within reasonable expectations, implying a majority of the patients were within standard inc/exc criteria. The high level of unrelated SAEs during the consent period and initial enrollment period indicate this may not be a suitable population to properly assess drug safety. Subgroup statistical analyses may be more relevant than ITT medians since several comorbidities, such as biliary obstruction, have elsewhere been demonstrated to have a dramatic impact on OS. Clinical trial information: NCT03512756