TY - JOUR
T1 - Phase I/IIa Trial in Advanced Pancreatic Ductal Adenocarcinoma Treated with Cytotoxic Drug-Packaged, EGFR-Targeted Nanocells and Glycolipid-Packaged Nanocells
AU - Ganju, Vinod
AU - Marx, Gavin
AU - Pattison, Scott
AU - Amaro-Mugridge, Nancy B.
AU - Zhao, Jing Ting
AU - Williams, Bryan R.G.
AU - MacDiarmid, Jennifer A.
AU - Brahmbhatt, Himanshu
N1 - Publisher Copyright:
© 2023 American Association for Cancer Research.
PY - 2024/1/15
Y1 - 2024/1/15
N2 - Purpose: We assessed the safety and efficacy of an EGFR-targeted, super-cytotoxic drug, PNU-159682-packaged nanocells with a-galactosyl ceramide-packaged nanocells (E-EDV-D682/GC) in patients with advanced pancreatic ductal adenocarcinoma (PDAC) who had exhausted all treatment options. Patients and Methods: ENG9 was a first-in-man, single-arm, open-label, phase I/IIa, dose-escalation clinical trial. Eligible patients had advanced PDAC, Eastern Cooperative Oncology Group status 0 to 1, and failed all treatments. Primary endpoints were safety and overall survival (OS). Results: Of 25 enrolled patients, seven were withdrawn due to rapidly progressive disease and one patient withdrew consent. All 25 patients were assessed for toxicity, 24 patients were assessed for OS, which was also assessed for 17 patients completing one treatment cycle [evaluable subset (ES)]. Nineteen patients (76.0%) experienced at least one treatment-related adverse event (graded 1 to 2) resolving within hours. There were no safety concerns, dose reductions, patient withdrawal, or treatment-related deaths. Median OS (mOS) was 4.4 months; however, mOS of the 17 ES patients was 6.9 months [208 days; range, 83–591 days; 95.0% confidence interval (CI), 5.6–10.3 months] and mOS of seven patients who did not complete one cycle was 1.8 months (54 days; range, 21–72; 95.0% CI, 1.2–2.2 months). Of the ES, 47.1% achieved stable disease and one partial response. Ten subjects in the ES survived over 6 months, the longest 19.7 months. During treatments, 82.0% of the ES maintained stable weight. Conclusions: E-EDV-D682/GC provided significant OS, minimal side effects, and weight stabilization in patients with advanced PDAC. Advanced PDAC can be safely treated with super-cytotoxic drugs via EnGeneIC Dream Vectors to overcome multidrug resistance.
AB - Purpose: We assessed the safety and efficacy of an EGFR-targeted, super-cytotoxic drug, PNU-159682-packaged nanocells with a-galactosyl ceramide-packaged nanocells (E-EDV-D682/GC) in patients with advanced pancreatic ductal adenocarcinoma (PDAC) who had exhausted all treatment options. Patients and Methods: ENG9 was a first-in-man, single-arm, open-label, phase I/IIa, dose-escalation clinical trial. Eligible patients had advanced PDAC, Eastern Cooperative Oncology Group status 0 to 1, and failed all treatments. Primary endpoints were safety and overall survival (OS). Results: Of 25 enrolled patients, seven were withdrawn due to rapidly progressive disease and one patient withdrew consent. All 25 patients were assessed for toxicity, 24 patients were assessed for OS, which was also assessed for 17 patients completing one treatment cycle [evaluable subset (ES)]. Nineteen patients (76.0%) experienced at least one treatment-related adverse event (graded 1 to 2) resolving within hours. There were no safety concerns, dose reductions, patient withdrawal, or treatment-related deaths. Median OS (mOS) was 4.4 months; however, mOS of the 17 ES patients was 6.9 months [208 days; range, 83–591 days; 95.0% confidence interval (CI), 5.6–10.3 months] and mOS of seven patients who did not complete one cycle was 1.8 months (54 days; range, 21–72; 95.0% CI, 1.2–2.2 months). Of the ES, 47.1% achieved stable disease and one partial response. Ten subjects in the ES survived over 6 months, the longest 19.7 months. During treatments, 82.0% of the ES maintained stable weight. Conclusions: E-EDV-D682/GC provided significant OS, minimal side effects, and weight stabilization in patients with advanced PDAC. Advanced PDAC can be safely treated with super-cytotoxic drugs via EnGeneIC Dream Vectors to overcome multidrug resistance.
KW - Therapy
KW - Obesity
KW - Worsens
KW - Mortality
KW - Minicells
KW - Cachexia
KW - Criteria
KW - Independent determinant
KW - Cancer
KW - Guidelines
UR - http://www.scopus.com/inward/record.url?scp=85182724521&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-23-1821
DO - 10.1158/1078-0432.CCR-23-1821
M3 - Article
SN - 1078-0432
VL - 30
SP - 304
EP - 314
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -