GVAX Pancreas (allogeneic GM-CSF-secreting tumor cells) / Novartis - LARVOL DELTA

The Possible Role of Immunotherapy in Locally Advanced Pancreatic Cancer Treatment. (PubMed, Acta Med Acad) - "LAPC remains one of the deadliest malignancies, with immunotherapy offering potential but constrained by limited survival benefits and adverse effects. Further studies focusing on novel agents, refined combinations, and overcoming tumor resistance mechanisms are critical to improve outcomes for this challenging disease."

Journal • Review • Oncology • Pancreatic Cancer • Solid Tumor

Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas (clinicaltrials.gov) - P2 | N=76 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Oct 2025 ➔ May 2026

IO biomarker • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Trial of Neoadjuvant and Adjuvant Nivolumab and BMS-813160 With or Without GVAX for Locally Advanced Pancreatic Ductal Adenocarcinomas. (clinicaltrials.gov) - P1/2 | N=46 | Completed | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2024 ➔ Feb 2025 | Trial primary completion date: Sep 2024 ➔ Feb 2025

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Boost GVAX Pancreas Vaccine With or Without CY in Patients With Pancreas Cancer (clinicaltrials.gov) - P2 | N=71 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2025 ➔ Aug 2026

Trial completion date • Head and Neck Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas (clinicaltrials.gov) - P2 | N=76 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Comparing Neoadjuvant/Adjuvant GVAX vs a mKRASvax Given With Anti-PD-1 and Anti-CD137 for Surgically Resectable Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=38 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • KRAS

A phase II study of neoadjuvant GVAX and cyclophosphamide combined with nivolumab and SBRT followed by surgery in borderline resectable pancreatic adenocarcinoma. (PubMed, Clin Cancer Res) - "The addition of combined immunotherapy and SBRT was safe and feasible in this patient population. No difference was observed in the mean CD8 T cell density between study patients and historical controls. These findings support the need for better characterization of how neoadjuvant immunotherapy may shift the phenotype of the PDAC TME."

Journal • P2 data • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • CD8 • CSF2

Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas (clinicaltrials.gov) - P2 | N=76 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2026 ➔ May 2026

IO biomarker • Trial completion date • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Clinical outcomes of immunotherapy in metastatic pancreatic carcinoma: A systematic review and meta-analysis. (ASCO-GI 2025) - "Immunotherapies included were GVAX, tremelimumab, Mesothelin-specific Chimeric Antigen Receptor T cells, durvalumab, pembrolizumab, canerpaturev, Sotigalimab, nivolumab, CO-1.01, allogeneic natural killer cell immunotherapy, Anti-EGFR chimeric antigen receptor-modified T cells, bispecific antibody armed T cells, and clivatuzumab tetraxetan... This meta-analysis demonstrates that novel immunotherapies have promising results on metastatic pancreatic cancer. Future new clinical trials with a follow-up on current early-phase results are needed."

Clinical data • Metastases • Retrospective data • Review • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • MSLN

The impact of KRAS mutations on the clinical outcome and immune response following immunotherapy for pancreatic cancer. (PubMed, Ann Pancreat Cancer) - P2 | "We identified a total of 30 patients from cohorts A: GVAX, an allogeneic whole cell cancer vaccine (n=16) and B: GVAX + anti-PD-1 (nivolumab) (n=14) with known KRAS mutation status and survival outcomes...With the addition of anti-PD-1 in Arm B, patients with KRAS G12D mutant disease had a lower ratio of CD8+ GZMB+/CD8+ T lymphocytes (P=0.005). KRAS G12D mutated PDAC represents a unique subtype of disease with decreased survival and lower ratio of activated CD8+ T lymphocytes as denoted by granzyme B (GZMB) positivity following GVAX/aPD-1 treatment."

Clinical data • IO biomarker • Journal • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • GZMB • KRAS

Comparing Neoadjuvant/Adjuvant GVAX vs a mKRASvax Given With Anti-PD-1 and Anti-CD137 for Surgically Resectable Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=38 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

IO biomarker • New P1/2 trial • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD20

CD137 agonism enhances anti-PD1 induced activation of expanded CD8+ T cell clones in a neoadjuvant pancreatic cancer clinical trial. (PubMed, iScience) - "Addition of CD137 agonist increased abundance of clonally expanded CD8+ T cells and increased immunosuppressive TREM2 signaling in tumor associated macrophages (TAMs), identified by comparison of ligand-receptor networks, corresponding to changes in metabolism and ECM interactions. These findings associate therapy with GVAX, anti-PD1, and CD137 agonist with enhanced CD8+ T cell function while inducing alternative immunosuppressive pathways in patients with PDAC."

IO biomarker • Journal • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • CSF2 • TNFRSF9

Trial of Neoadjuvant and Adjuvant Nivolumab and BMS-813160 With or Without GVAX for Locally Advanced Pancreatic Ductal Adenocarcinomas. (clinicaltrials.gov) - P1/2 | N=46 | Completed | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting ➔ Completed | N=30 ➔ 46 | Trial completion date: Dec 2024 ➔ Sep 2024 | Trial primary completion date: Dec 2024 ➔ Sep 2024

Enrollment change • Metastases • Trial completion • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • TNFRSF9

Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas (clinicaltrials.gov) - P2 | N=76 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2025 ➔ Aug 2026 | Trial primary completion date: Dec 2024 ➔ Aug 2025

IO biomarker • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD8 • GZMB • IL17A • PD-1 • TNFRSF9

Phase I Study of Adjuvant Allogeneic GM-CSF-Transduced Pancreatic Tumor Cell Vaccine, Low Dose Cyclophosphamide, and SBRT followed by FFX in High-Risk Resected Pancreatic Ductal Adenocarcinoma. (PubMed, Int J Radiat Oncol Biol Phys) - "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."

Journal • P1 data • Tumor cell • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Thrombocytopenia • CSF2

Spatial multi-omics reveal humoral immunity niches associated with tertiary lymphoid structures in pancreatic cancer pathologic responders to neoadjuvant immunotherapy (SITC 2024) - P2 | "Conclusions Our study navigates the molecular landscape, cellular heterogeneity and tissue architecture of the TLS-enriched PDAC tumor microenvironment. Our findings shed light on the plasticity of TLS to augment immunotherapy responses in solid tumors prompting new treatment strategies targeting humoral immunity and ECM remodeling (figure 1)."

Clinical • IO biomarker • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Spatial multi-omics reveal humoral immunity niches associated with tertiary lymphoid structures in pancreatic cancer pathologic responders to neoadjuvant immunotherapy (SITC 2024) - P2 | "Conclusions Our study navigates the molecular landscape, cellular heterogeneity and tissue architecture of the TLS-enriched PDAC tumor microenvironment. Our findings shed light on the plasticity of TLS to augment immunotherapy responses in solid tumors prompting new treatment strategies targeting humoral immunity and ECM remodeling (figure 1)."

Clinical • IO biomarker • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Spatial multi-omics reveal humoral immunity niches associated with tertiary lymphoid structures in pancreatic cancer pathologic responders to neoadjuvant immunotherapy (SITC 2024) - P2 | "Conclusions Our study navigates the molecular landscape, cellular heterogeneity and tissue architecture of the TLS-enriched PDAC tumor microenvironment. Our findings shed light on the plasticity of TLS to augment immunotherapy responses in solid tumors prompting new treatment strategies targeting humoral immunity and ECM remodeling (figure 1)."

Clinical • IO biomarker • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer (clinicaltrials.gov) - P2 | N=41 | Completed | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting ➔ Completed

Metastases • Trial completion • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • STAT6

Pancreatic Tumor Cell Vaccine (GVAX), Cyclophosphamide, SBRT, and FOLFIRINOX in Patients With Resected Adenocarcinoma of the Pancreas (clinicaltrials.gov) - P2 | N=19 | Completed | Sponsor: 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

Phase classification • Trial completion • Trial completion date • Trial primary completion date • Tumor cell • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Trial of Boost Vaccinations of Pancreatic Tumor Cell Vaccine (clinicaltrials.gov) - P2 | N=71 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2024 ➔ Jul 2025

Trial completion date • Tumor cell • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

THE RATIONALE OF REPROGRAMMING TREM2+ MACROPHAGES FOR OVERCOMING THE RESISTANCE TO IMMUNE CHECKPOINT INHIBITORS IN PANCREATIC ADENOCARCINOMA (APCM 2024) - "We also examined the relationship between TREM2 expression and effector T cells in surgically resected human PDAC collected from a previous clinical trial treated with the neoadjuvant combination therapy of nivolumab(anti-PD-1 antibody), urelumab(antiCD137 agonist antibody), and the pancreatic cancer GVAX vaccine... Our study demonstrates the anti-tumor efficacy of anti-TREM2 antibody in combination with an immune checkpoint inhibitor in mouse PDAC. However, the analysis of human PDAC following neoadjuvant immunotherapy suggests that TREM2 on TAMs may be activated following the activation of effector T cells. Taken together, our results suggest that TREM2+ TAMs should be reprogrammed instead of being depleted in the design of anti-TREM2-based therapy for PDAC."

Checkpoint inhibition • IO biomarker • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • GZMB • TREM2

The rationale of reprogramming TREM2+ macrophages for overcoming the resistance to immune checkpoint inhibitors in pancreatic adenocarcinoma. (ASCO 2024) - "TREM2 was stained on slides which were previously obtained from surgically resected PDACs following the neoadjuvant combination treatment of nivolumab, urelumab, and GVAX and stained for multiple immune cell markers with a multiplex staining-striping immunohistochemistry (IHC) technique... Our study demonstrates the anti-tumor efficacy of anti-TREM2 antibody in combination with an immune checkpoint inhibitor in mouse PDAC. However, the analysis of human PDAC following neoadjuvant immunotherapy suggests that TREM2 on TAMs may be activated following the activation of effector T cells. Taken together, our results suggest that TREM2+ TAMs should be reprogrammed instead of being depleted in the design of anti-TREM2-based therapy for PDAC."

Checkpoint inhibition • IO biomarker • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD8 • GZMB • TREM2

Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2024 ➔ Aug 2024

Metastases • Trial completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • STAT6

Safety and immunologic impact of neoadjuvant/adjuvant GM-CSF-secreting allogenic pancreatic tumor cell vaccine (GVAX) combined with cyclophosphamide, pembrolizumab, and macrophage-targeting CSF1R inhibitor IMC-CS4 in pancreatic adenocarcinoma (AACR 2024) - P2 | "The triplet was safe and significantly increased activated CD8+ T cells suggesting the combination can induce an effector T cell response. Decreased granulocyte levels correlated with PR."

Clinical • Tumor cell • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • CEACAM8 • CSF1R • CSF2 • GZMB • PD-L1