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

A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma. (PubMed, Nat Commun) - P2 | "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."

Combination therapy • IO biomarker • Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD8 • IL17A • PD-1

Nivolumab and a CCR2/CCR5 dual antagonist (BMS-813160) with or without GVAX for locally advanced pancreatic ductal adenocarcinomas: Results of phase I study. (ASCO-GI 2023) - P1/2 | " 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."

Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CCR2 • CD8 • TNFRSF9

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

Multi-omic analyses of changes in the tumor microenvironment of pancreatic adenocarcinoma following neoadjuvant treatment with anti-PD-1 therapy. (PubMed, Cancer Cell) - "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."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Gastrointestinal Cancer • Hepatology • Immune Modulation • Inflammation • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD4 • CD8 • ITGAM • TNFRSF9

A randomized phase II study: CRS207/GVAX plus anti-PD1 and anti-CTLA4 recruits mesothelin- and mKRAS-specific T cells into PDAC. (PubMed, Cancer Immunol Res) - P2 | "High myeloid and Treg signatures correlated with poor responses. We conclude that GVAX/CRS-207 plus nivolumab and ipilimumab successfully generates and expands T-cell clones specific to mesothelin and mutant KRAS within the PDAC TME but immunotherapy-induced myeloid-cell enrichment remains a barrier to greater efficacy."

IO biomarker • Journal • P2 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS • MSLN

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

Adjuvant multimodality immunotherapy in resected high-risk pancreatic ductal adenocarcinoma. (PubMed, Transl Gastroenterol Hepatol) - No abstract available

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Efficacy and safety of GVAX pancreas vaccine with CRS-207 in pretreated metastatic pancreatic adenocarcinoma: A systematic review and meta-analysis. (ASCO 2026) - "In patients with pretreated metastatic pancreatic adenocarcinoma, the GVAX/CRS-207 prime-boost vaccine regimen was tolerable but did not confer a statistically significant improvement in overall survival (HR = 0.75, 95% CI: 0.30–1.92; P = 0.55) compared to control therapy. The available evidence is limited, and the high statistical heterogeneity observed among studies hinders definitive conclusions. Therefore, future research should focus on biomarker-driven patient selection and rational combination strategies to enhance vaccine efficacy."

IO biomarker • Metastases • Retrospective data • Review • Oncology • Pancreatic Adenocarcinoma • Pancreatic Ductal Adenocarcinoma • CSF2 • MSLN

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 completion date: May 2026 ➔ Sep 2026 | Trial primary completion date: May 2026 ➔ Sep 2026

IO biomarker • Trial completion date • 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=22 | Completed | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=46 ➔ 22

Enrollment change • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Adjuvant immunotherapy in resected pancreatic ductal denocarcinoma: A 25-year landscape analysis of ClinicalTrials.gov (2000-2025) (AACR 2026) - "Immunotherapy approaches were mainly vaccines (GVAX, TG-01, ELI-002) and immune modulators, with only one small trial testing a checkpoint inhibitor (CT-011). Over two decades, adjuvant immunotherapy in PDAC has not advanced beyond small, exploratory studies. Over two decades, adjuvant immunotherapy in PDAC has not advanced beyond small, exploratory studies. Trials were underpowered, academic-led, and focused largely on vaccine-based strategies, with minimal checkpoint inhibitor evaluation and no definitive phase 3 programs. Adequately powered, industry-supported phase 3 trials are urgently needed to establish effective adjuvant immunotherapy strategies in resected PDAC."

Clinical • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor

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) - "Abstract is embargoed at this time."

Clinical • Tumor cell • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CSF2

Machine learning integrating spatial omics uncovers humoral immunity patterns in intratumoral tertiary lymphoid structures in pancreatic cancer pathologic responders (AACR 2024) - P2 | "We present machine learning approaches for spatial multi-omics analysis to characterize the TLS-enriched TME. We mined genome-wide spatial TLS gene expression patterns elucidating the spatial dynamics of humoral immunity of rare immunotherapy pathologic responders in PDAC. Altogether our findings shed light on the plasticity of TLS in neoadjuvant immunotherapy and suggest future immunotherapy approaches should target both humoral and cytotoxic NK/T cell compartments to augment responses in solid tumors."

IO biomarker • Machine learning • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CSF2

Safety and immunologic impact of neoadjuvant/adjuvant GVAX, cyclophosphamide, pembrolizumab, and anti-CSF1R agent IMC-CS4 in pancreatic adenocarcinoma. (PubMed, Front Immunol) - P1 | "CI has a manageable safety profile and leads to increased intratumoral cytotoxic effector T cells. https://clinicaltrials.gov/study/NCT03153410, identifier NCT03153410."

Clinical • Journal • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD8 • CSF1R • CSF2 • PD-L1

The combination of a cancer vaccine, pembrolizumab, and stereotactic body radiation in patients with locally advanced pancreatic cancer: a single-arm, phase II study. (PubMed, Nat Commun) - P2 | "However, patients with unresectable disease still maintained significantly worse DMFS and OS. The regimen demonstrated a manageable safety profile."

Journal • P2 data • Oncology • Pancreatic Cancer • Solid Tumor • CSF2

Cytometric Atlas of Combination Immunotherapy in Pancreatic Cancer: Blood-Based Signatures Reveal Vaccine and Checkpoint Inhibitor Responses. (PubMed, Cancer Immunol Res) - "Vaccine-mediated effects were similar, but GVAX promoted plasmacytoid dendritic cells more than CRS-207. Derived phenotypic patterns could also be projected onto tumor imaging data, underscoring the potential for discoveries relating treatment-induced peripheral signatures to changes in the tumor microenvironment."

Checkpoint inhibition • IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

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