GVAX Pancreas (allogeneic GM-CSF-secreting tumor cells)

This is the first prospective trial to evaluate adjuvant GVAX, Cy, SBRT, and mFFX in resected PDAC patients with high-risk features. This combination regimen was well tolerated with limited toxicity and promising survival outcomes, warranting future studies to validate this regimen in the adjuvant setting.

P2, N=41, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed

P2, N=19, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed | Phase classification: PN/A --> P2 | Trial completion date: Sep 2024 --> Oct 2023 | Trial primary completion date: Sep 2024 --> Oct 2023

P2, N=71, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2024 --> Jul 2025

P2, N=41, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2024 --> Aug 2024

P2, N=28, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Feb 2024 | Trial primary completion date: Sep 2024 --> Feb 2024

P1/2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

Adding SBRT to GVAX/a-PD-1 shortens the distances from PD-1+CD8+ T cells to tumor cells and to PD-L1+ myeloid cells, which portends prolonged survival. These findings have guided the design of next radioimmunotherapy studies by targeting M2-like TAM in PDACs.

P1, N=12, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed

P2, N=40, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2023 --> Dec 2024

P2, N=71, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2023 --> Aug 2024 | Trial primary completion date: Aug 2023 --> Aug 2024

P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2023 --> Sep 2023 | Trial primary completion date: Jun 2023 --> Sep 2023

We enrolled patients with resectable pancreatic adenocarcinoma into such a platform trial (NCT02451982) to receive pancreatic cancer GVAX vaccine with low-dose cyclophosphamide alone (Arm A; n = 16), with anti-PD-1 antibody nivolumab (Arm B; n = 14), and with both nivolumab and anti-CD137 agonist antibody urelumab (Arm C; n = 10), respectively...GVAX+nivolumab+urelumab demonstrates numerically-improved disease-free survival (HR = 0.55, p = 0.242; HR = 0.51, p = 0.173) and overall survival (HR = 0.59, p = 0.377; HR = 0.53, p = 0.279) compared to GVAX and GVAX+nivolumab, respectively, although not statistically significant due to small sample size. Therefore, neoadjuvant and adjuvant GVAX with PD-1 blockade and CD137 agonist antibody therapy is safe, increases intratumoral activated, cytotoxic T cells, and demonstrates a potentially promising efficacy signal in resectable pancreatic adenocarcinoma that warrants further study.

P2, N=76, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2024 --> Dec 2025 | Trial primary completion date: Jun 2023 --> Dec 2024

We compared specimens from 3 treatment arms for downstream analysis: Arm A: an allogeneic whole cell vaccine, GVAX (n=7); Arm B: GVAX and nivolumab (n=4); Arm C: GVAX, nivolumab, and urelumab (n=4)... Analysis of combination GVAX, PD-1 inhibition and CD137 agonist therapy demonstrated changes in multiple immune cell proportions and their functional pathways. These data provide new evidence that PDACs can become T cell rich and respond to combination immunotherapies.

P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jan 2023 --> Jun 2023 | Trial primary completion date: Jan 2023 --> Jun 2023

P2, N=61, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Completed --> Active, not recruiting | Trial completion date: Oct 2022 --> Aug 2023

P1/2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2023 --> Dec 2023 | Trial primary completion date: Mar 2023 --> Dec 2023

P2, N=40, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

This open-label, single center two-arm phase I/II trial uses neoadjuvant/adjuvant nivolumab and BMS-813160 +/- GVAX following 8 to 16 doses of FOLFIRINOX and SBRT in patients with newly diagnosed LAPC... We determined that nivolumab 480mg IV q4 weeks, GVAX 5x108 cells intradermal q4 weeks, and BMS-813160 300mg PO BID were the RP2D for the phase 2 portion of this investigation which is ongoing. This combination appears safe and neoadjuvant use does not lead to delay in surgery. Clinical trial information: NCT03767582.

P2, N=61, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed

Bulk and single-cell RNA sequencing found that nivolumab alters CD4 T cell chemotaxis signaling in association with CD11b neutrophil degranulation, and CD8 T cell expression of CD137 was required for optimal T cell activation. These findings provide insights into PD-1-regulated immune pathways in PDAC that should inform more effective therapeutic combinations that include TAN regulators and T cell activators.

P2, N=56, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Dec 2022 --> Oct 2021

P2, N=40, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting

P2, N=44, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2023 --> Dec 2022 | Trial primary completion date: Mar 2023 --> Dec 2022

P2, N=63, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jul 2023 --> Sep 2022 | Trial primary completion date: Jul 2023 --> Sep 2022

P2, N=63, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Oct 2023 --> Jul 2023 | Trial primary completion date: Oct 2023 --> Jul 2023

P2, N=63, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting

P2, N=44, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2022 --> Mar 2023 | Trial primary completion date: Feb 2022 --> Mar 2023

P2, N=56, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022

P1/2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2022 --> Mar 2023 | Trial primary completion date: Mar 2022 --> Mar 2023

P=N/A, N=19, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2021 --> Sep 2024 | Trial primary completion date: Dec 2021 --> Sep 2024

P2, N=76, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Phase classification: P1/2 --> P2

P1/2, N=76, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2023 --> Jun 2024 | Trial primary completion date: Jun 2022 --> Jun 2023

P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting

P=N/A, N=19, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2021 --> Dec 2021 | Trial primary completion date: Aug 2021 --> Dec 2021

P2, N=56, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jul 2021 --> Dec 2021 | Trial primary completion date: Jul 2021 --> Dec 2021

P2, N=44, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=70 --> 44

P2, N=70, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2023 --> Feb 2022 | Trial primary completion date: Feb 2021 --> Feb 2022

Gemcitabine with GVAX and anti-PD1 with or without anti-CSF-1R also improved the infiltration of effector CD8+ T-cells, and the presence of anti-CSF-1R in the chemo-immunotherapy regimens decreased the infiltration of myeloid cells. The overlapping mechanisms of the components in the chemo-immunotherapy regimens may explain the lack of survival difference between the various regimens, and this remains to be explored.