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

CI has a manageable safety profile and leads to increased intratumoral cytotoxic effector T cells. https://clinicaltrials.gov/study/NCT03153410, identifier NCT03153410.

However, patients with unresectable disease still maintained significantly worse DMFS and OS. The regimen demonstrated a manageable safety profile.

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.

P2, N=76, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Oct 2025 --> May 2026

P1/2, N=46, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2024 --> Feb 2025 | Trial primary completion date: Sep 2024 --> Feb 2025

P2, N=71, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2025 --> Aug 2026

P2, N=76, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting

P1/2, N=38, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

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.

P2, N=76, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2026 --> May 2026

P1/2, N=38, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.