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

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.

While the study did not meet its primary endpoint of improvement in OS of Arm A over Arm B, the OS was comparable to standard therapy. Objective responses and immunologic changes in the tumor microenvironment were evident.