Ongoing Survival Analysis of DOC1021 for Treatment of Resectable or Borderline Resectable Pancreatic Ductal Adenocarcinoma — ASN Events

Ongoing Survival Analysis of DOC1021 for Treatment of Resectable or Borderline Resectable Pancreatic Ductal Adenocarcinoma (#272)

Vanaja Konduri 1 2 , Akshar Trivedi 1 , Wei Liu 1 , Madhuri Namekar 1 , Keenan J Ernste 1 , Glenn G Wilson 1 , Elizabeth Duus 2 , Tannaz Armaghany 1 , Shalini U Makawita 1 , Ernest R Camp 1 , George Van Buren 1 , Laura Aguilar 2 , Benjamin L Musher 1 , William K Decker 1 2
  1. Baylor College of Medicine, Houston, TEXAS, United States
  2. Diakonos Oncology Corporation, Houston, TX, United States

While recent advances in the treatment of pancreatic ductal adenocarcinoma (PDAC) have improved median OS, PDAC remains highly lethal, with 5-year overall survival < 50% even for patients who undergo aggressive surgery and chemotherapy. DOC1021 is a cell-based immunotherapy derived from the full complement of autologous tumor antigens. It leverages p38MAPK and mTORC1 signaling cascades to initiate phenotypic cDC1-like skewing of monocyte-derived DC, generating downstream development of CD8+ tissue-homing, cytolytic memory effectors. Here we report extended survival results from a phase I study cohort in which patients with potentially resectable PDAC received DOC1021 after surgical resection and standard neoadjuvant/adjuvant therapy. To prepare DOC1021, patient monocyte-derived DC were loaded with autologous tumor lysate and amplified tumor mRNA extracted from resected tumor. After completion of adjuvant therapy, DOC1021 was administered biweekly via CT-guided injection near lymph nodes in the post-operative surgical bed in conjunction with weekly subcutaneous peg-IFN. Blood was collected before and ~5 weeks after DOC1021 administration to assess peripheral immune responses. Seven patients (median age: 58 years, range: 49–71) received DOC1021 after R0 (71%) or R1 resection (29%) and standard neoadjuvant and/or adjuvant therapy. At the time of analysis, 5 patients are alive, 3 of whom remain relapse-free. Two patients have reached or are approaching 5 years of post-operative survival, with three additional patients under active follow-up at approximately 22 to 44 months post-surgery. The most common DOC1021-related adverse events were mild flu-like symptoms, with no dose-limiting toxicities observed. Post-vaccination, patients exhibited upregulation of CD127+ memory precursor effector cells (MPECs) with additional upregulation of granzyme B and IFN-γ expression in circulating CD8+ and CD4+ cells, respectively. DOC1021 can be safely delivered after PDAC resection and standard perioperative therapy with increasingly encouraging survival outcomes. A second study arm evaluating vaccination post-surgery but prior to adjuvant therapy is now open and accruing.