NCT04739618

Metastatic Solid Cancer Clinical Trial

A Phase 2 Trial of Non-ablative Cryosurgical Freezing and Multiplex Immunotherapy in Patients With Metastatic Solid Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Sponsor: ImmunSYS, LLC · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study seeks to estimate the potential efficacy of the study treatment, as well as the occurrence of adverse events.

Detailed description

Non-ablative Cryosurgical Freezing (limited to 1.5 cm diameter single freeze within the cancer (up to two cancer sites selected and treated)) will release intact antigens to prime the immune system. The study treatment immunotherapeutic drugs (PD-1 inhibitor monoclonal antibody Keytruda (pembrolizumab), anti-CTLA-4 monoclonal antibody ipilimumab, and GM-CSF) will then be sequentially injected directly into each of the treated cancer sites immediately following Non-ablative Cryosurgical Freezing. Daily subcutaneous GM-CSF injections will also be administered subsequently. It is speculated that neoantigens released from the cryo-frozen necrotic cancer will be available in the vicinity of the Non-ablative Cryosurgical Freezing field immediately following the procedure. Immature dendritic cells attracted to the injection site will internalize neoantigens to become activated to recognize cancer-specific antigenic proteins. The activated dendritic cells will recruit killer T-cells to the injection site to attack cancer cells, and then migrate through the lymphatic system to sites of metastases, targeting cancer-specific neoantigens and recruiting more killer T-lymphocytes to destroy other cancer cells harboring the precise antigenic epitopes (abscopal (bystander) effect). In this way, dendritic cells are capable of initiating cell-mediated systemic immune response in combination with cytotoxic killer T-cells. Regulatory T lymphocytes, which have been implicated in dampening or halting cell-mediated, antigen-specific immune responses, will be selectively depleted by anti-CTLA-4 monoclonal antibodies, intra-tumoral GM-CSF, and GM-CSF. Intra-tumoral injection of the immunotherapeutic medications assists in stimulating and harnessing the local and systemic immune response. GM-CSF prolongs the immune response. Using this combination of therapies, referred to as YourVaccxTM, it is thought that a clinically significant systemic anti-cancer immune response might be elicited. Intra-tumoral injection of drugs will likely offer fewer side effects than systemic therapy.

Conditions

• Metastatic Cancer

Interventions

Type	Name	Description
DRUG	Keytruda Injectable Product	PD-1 inhibitor antibody
DRUG	Yervoy Injectable Product	Anti-CTLA-4 antibody
DRUG	GM-CSF	1 mL injected into each non-ablative cryosurgical freezing zone. Daily injection administered subcutaneously. 250 mcg daily injections for a total of 25 days after each treatment.
PROCEDURE	Non-ablative Cryosurgical freezing	To induce immediate necrosis and necroptosis and a rim of injured cancer cells, thereby exposing a complete range of patient-specific tumor antigens that are specific to the treated subject.

Timeline

• Start date: 2021-03-04
• Primary completion: 2024-12-01
• Completion: 2024-12-01
• First posted: 2021-02-04
• Last updated: 2024-07-23

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study