CRS-207 / Novartis - LARVOL DELTA

Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Hepatology • 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

Reprogramming and selective recruitment of distinct neutrophil subpopulations restrain cancer metastasis* (AACRPanCa 2024) - P2 | "In both mouse models of liver and lung metastasis, small molecule inhibition of CXCR2 using SX-682 led to enrichment of CXCR2low neutrophils and reduced metastatic burden in TumorAg ON PDAC...Indeed, in a highly immune-resistant model of PDAC, 6419c5, the use of tumor-targeting listeria vaccine CRS-207 along with CXCR2 inhibition significantly reduced metastatic burden, whereas CXCR2 inhibitor or CRS-207 alone had no impact...Consistent with our mouse model results, IMC analysis revealed increased proportion of MPOhigh NOS2high neutrophils upon treatment, suggesting that induction of tumor antigen response results in an effective remodeling of the neutrophil compartment . Taken together, our results show that neutrophils may acquire anti-tumor properties under appropriate inflammatory conditions and that distinct subpopulations of neutrophils may be leveraged for the treatment of metastatic disease."

Clinical • IO biomarker • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS • NOS2 • TP53

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

Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2024 ➔ Apr 2024

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • 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=40 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2023 ➔ Dec 2024

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

Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Dec 2023 ➔ Aug 2023

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

Con - Raphael Bueno Is Right (It Does Not Work) (IASLC-WCLC 2019) - P1, P2, P2/3, P3; "...Combination chemotherapy with platinum/antifolate –either pemetrexed or raltitrexed- is the only standard of care 1st line treatment with proven improvement of survival, which varies according to series and patient selection between 12-16 months median overall survival (mOS), with corresponding 1 year survival rate of 50-60%...The randomized DETERMINE trial evaluated in 564 patients the anti–CTLA-4 antibody tremelimumab versus placebo in second or third line and found no benefit in outcome (hazard ratio 0.92; p = 0.408). Results from the anti–PD-1 or anti–PD-L1 trials with nivolumab, pembrolizumab and durvalumab are fairly consistent with a response rate of 19-30%, a median PFS of 3.5 – 6.0 months and mOS of 12-18 m, all uncontrolled in selected patients with good prognostic features...The DREAM trial, a single-arm, open-label phase II trial of durvalumab with cisplatin/pemetrexed, followed by durvalumab maintenance therapy for 1 year...The phase III CheckMat

IO biomarker • PD(L)-1 Biomarker • Tumor mutational burden • Lung Cancer • Mesothelioma • Oncology • Solid Tumor • Thoracic Cancer

Study of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cy) in Patients With Pancreatic Cancer (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Completed ➔ Active, not recruiting | Trial completion date: Oct 2022 ➔ Aug 2023

Enrollment closed • Trial completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CA 19-9

Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

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

First-In-Human Study of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, for Non-Small Cell Lung Cancer (WCLC 2017) - P1; "The RP2D of JNJ-757 is 10[9] CFU, with a safety profile consistent with other LADD Lm-based agents such as CRS-207. Both innate and mesothelin-specific adaptive immune responses were demonstrated in multiple patients. Recruitment in the trial continues to further characterize the safety profile and immune response, and a phase 1b/2 trial with JNJ-757 and nivolumab is planned."

Non Small Cell Lung Cancer

A phase II single-arm study of CRS-207 with pembrolizumab (pembro) in previously treated malignant pleural mesothelioma (MPM). (ASCO-SITC 2019) - P1, P1b, P2; " Adults with epithelial/biphasic MPM, ≤2 prior lines, progression on pemetrexed and platinum-based therapy, and no prior immunotherapies were enrolled. The toxicity profile of CRS-207/pembro combination was consistent with the safety profile of each component alone. No evidence of clinical activity was observed. Based on the results and an overall evaluation of the program, the clinical development of CRS-207 was discontinued."

P2 data • Lung Cancer • Mesothelioma • Oncology • Solid Tumor • Thoracic Cancer

A phase 2 trial of CRS-207 and pembrolizumab in adults with recurrence of metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinomas. (ASCO-GI 2018) - No abstract available.

Clinical • P2 data • Esophageal Cancer • Gastric Cancer

Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CA 19-9

Study of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cy) in Patients With Pancreatic Cancer (clinicaltrials.gov) - P2 | N=61 | Completed | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting ➔ Completed

Trial completion • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CA 19-9

Results from a phase 2b, randomized, multicenter study of GVAX pancreas and CRS-207 compared to chemotherapy in adults with previously-treated metastatic pancreatic adenocarcinoma (ECLIPSE Study). (ASCO-GI 2017) - P2b; "Low-dose cyclophosphamide (CY) is administered with GVAX to inhibit regulatory T cells. The combination of CY/GVAX + CRS-207 did not show a survival benefit over chemotherapy in patients with previously-treated mPDA, although survival of patients receiving CRS-207 alone appeared similar to chemotherapy. The regimens were well tolerated with no new significant safety findings. The high dropout rate in the chemotherapy arm demonstrates a potential challenge for conventional controls in immunotherapy trials."

Clinical • Biliary Cancer • Biosimilar • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Hepatology • 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=40 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CA 19-9

Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2023 ➔ Dec 2022 | Trial primary completion date: Mar 2023 ➔ Dec 2022

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Cancer antigen 19-9

Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2025 ➔ Dec 2023 | Trial primary completion date: Jun 2025 ➔ Dec 2023

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

Study of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cy) in Patients With Pancreatic Cancer (clinicaltrials.gov) - P2 | N=63 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jul 2023 ➔ Sep 2022 | Trial primary completion date: Jul 2023 ➔ Sep 2022

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Cancer antigen 19-9

Study of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cy) in Patients With Pancreatic Cancer (clinicaltrials.gov) - P2 | N=63 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Oct 2023 ➔ Jul 2023 | Trial primary completion date: Oct 2023 ➔ Jul 2023

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Cancer antigen 19-9

Study of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cy) in Patients With Pancreatic Cancer (clinicaltrials.gov) - P2 | N=63 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Cancer antigen 19-9

Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2022 ➔ Mar 2023 | Trial primary completion date: Feb 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Cancer antigen 19-9

Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2; N=20; Not yet recruiting; Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Trial completion date: Dec 2025 ➔ Apr 2025; Initiation date: Dec 2021 ➔ Apr 2022; Trial primary completion date: Dec 2025 ➔ Apr 2025

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor