NCT05116917

Immunotherapy Combined With Radiation and Influenza Vaccine for Pancreatic Cancer.

Nivolumab, Ipilimumab and Radiation in Combination With Influenza Vaccine in Patients With Pancreatic Cancer (INFLUENCE)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Herlev Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Pancreatic cancer (PC) remains a dreadful disease due to its often advanced stage at diagnosis and poor sensitivity to chemotherapy. Progression after 1. line chemotherapy is inevitable in patients with advanced PC, and treatment options for patients who progress after 1. line chemotherapy are limited. Considering the emerging role of the tumor microenvironment, the combination of checkpoint blocking antibodies with immunomodulation of the tumor microenvironment could lead to better responses in tumor historically resistant to radiation and checkpoint blocking antibody approaches as single modalities. Influenza vaccination in cancer patients receiving immune checkpoint inhibitors resulted in a better survival, irrespective of the anticancer treatment outcome. Influenza vaccine facilitates both T- and B cell activation and drives interferon-gamma response, supporting the rationale for combining of influenza vaccine with immune checkpoint inhibition and radiation (NCT02866383). Based on these considerations, the proposed treatment with SBRT of 15 Gy in combination with nivolumab, ipilimumab and influenza vaccine may have the potential to provide meaningful clinical benefit by generating durable clinical responses, thereby improving quality of life (QoL) and potentially extending survival.

Detailed description

Pancreatic cancer (PC) is the fourth leading cause of cancer death, and each year 1000 Danes are diagnosed with PC, 80% of which are advanced stage. Survival rates are meager, currently approaching 10% at 5 years postdiagnosis, and have scarcely improved over the last 50 years. PC is highly resistant to conventional treatments, and nearly all patients develop metastases and die. As the incidence of PC continuously rises while treatment response rates remain incredibly low, a lack of effective therapy options and accurate predictive biomarkers is a real cause for concern and underlines the need for further research in this area. Immunotherapy has not been successful in PC patients primarily due to a lack of pre-existing T-cell immunity and/or a highly immunosuppressive tumor microenvironment. "Non-immunogenicity" of PC with high prevalence of immunosuppressive cells and typically a scarcity of tumor-infiltrating effector lymphocytes is considered as one of the reasons for lacking responsiveness to single-agent immunotherapies. Considering the emerging role of the tumor microenvironment, the combination of checkpoint blocking antibodies with immunomodulation of the tumor microenvironment could lead to better responses in tumor historically resistant to radiation and checkpoint blocking antibody approaches as single modalities. Preliminary data from the phase 2 study CHECKPAC (NCT02866383) showed durable clinical benefit in a small subgroup of patients after the addition of stereotactic body radiation therapy (SBRT) of 15 Gy to the combination of nivolumab and ipilimumab (Herlev internal data) in patients with resistant metastatic PC. Influenza vaccination in cancer patients receiving immune checkpoint inhibitors inexplicably was associated with a better survival, irrespective of the anticancer treatment outcome. Influenza vaccine facilitates both T- and B cell activation and drives interferon-gamma response, supporting the rationale for combining of influenza vaccine with CHECKPAC strategy. Based on these considerations, the proposed treatment with nivolumab, ipilimumab and radiation in combination with influenza vaccine may potentially provide meaningful clinical benefit by generating durable clinical responses, thereby improving quality of life (QoL) and potentially extending survival.

Conditions

• Pancreatic Cancer

Interventions

Type	Name	Description
DRUG	Nivolumab	3 mg/kg (up to 240 mg maximum) will be given on day 1 (± 3 days) of each 14-day treatment cycle
DRUG	Ipilimumab	1 mg/kg will be given on day 1 cycle 1 (± 3 days) and once more after 6 weeks
BIOLOGICAL	Influenza vaccine	Seasonal influenza vaccine is given IM or via PharmaJet Stratis Needle-Free Injection System, 0.5 mL per dose as a single on day 1 cycle 1 (± 3 days)
RADIATION	SBRT	* A total dose of 15 Gy as a single fraction is prescribed as the mean dose to the PTV. * PTV should be covered by 95% isodose (PTV D99% \> 95%).

Timeline

• Start date: 2021-11-05
• Primary completion: 2023-10-19
• Completion: 2023-10-19
• First posted: 2021-11-11
• Last updated: 2024-05-28

Locations

1 site across 1 country: Denmark