Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Molgramostim

Sargramostim

Pembrolizumab

Immunomodulating Agents

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunologic Factors

Efficacy of Non-ablative Cryosurgical Freezing and Multiplex Immunotherapy as determined by overall response rate of radiographic changes according to iRECIST criteria

Keytruda Injectable Product

Yervoy Injectable Product

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.

GM-CSF

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.

Non-ablative Cryosurgical freezing

Stephanie Sumblin

Melanie Wilk, M.S.

Christine Lau, M.D.

David Bostwick, M.D., M.B.A.

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

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.

Male or female subjects greater than 18 years of age with histologically-proven metastatic cancer with at least one imaging- or histologically- proven metastases to lymph nodes, bone, or soft tissue.

Metastatic Solid Cancer Clinical Trial

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

rPFS as determined with both RECISTS1.1 and iRECIST criteria

Best overall response of confirmed PR or CR by independent radiology review

Time to cancer progression is measured from the date of first study treatment until the date of cancer progression.

Number and percent of participants that are alive.

An AE is any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity. Incidence was defined as the number of participants who experienced an adverse event within their period of participation in this study. Incidence of adverse events will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).

Data will be collected for the design of future studies.

Efficacy of Non-ablative Cryosurgical Freezing and Multiplex Immunotherapy as determined by overall response rate of radiographic changes according to iRECIST criteria.

Overall response rate as determined using RECIST1.1 radiographic response

ImmunSYS, LLC

Antirheumatic Agents

Cyclophosphamide

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Efficacy of Cryosurgical Freezing and Multiplex Immunochemotherapy as determined by overall response rate of radiographic changes according to iRECIST criteria.

Keytruda (pembrolizumab): PD-1 inhibitor antibody

Injectable 50mg/mL, only 2 mL injected.

Yervoy (ipilimumab): Anti-CTLA-4 antibody

Injectable 5mg/mL, only 2 mL injected.

Injectable 250mg/m2, only 1 mL injected. Oral low dose cyclophosphamide: 50mg once daily pill for 5 days prior to first treatment, 3 days prior to 2nd and 3rd treatment.

Cytoxan

Cryosurgery, also known as cryoablation, for metastatic cancer works by freezing the cancer cells inside the tumor. Cryoablation will release intact antigens to prime the immune system.

Cryosurgical freezing (cryosurgery)

Daily injection administered subcutaneously. 250 mcg daily injections for a total of 25 days post after each treatment.

GM-CSF Injectable

David G Bostwick, M.D., M.B.A.

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 nivolumab or pembrolizumab and anti-CTLA-4 monoclonal antibody ipilimumab, and low-dose cyclophosphamide) will then be sequentially injected directly into each of the treated cancer sites immediately following cryosurgical freezing. These injections will be performed in combination with collagen (Helitene) to improve drug containment at the site of injection for improved local effect rather than rapid disbursement and dilution throughout adjacent interstitial spaces, as well as sustained drug delivery over time rather than a burst-release pattern. Prior to study treatment, oral low dose cyclophosphamide will be given. Post-treatment, daily subcutaneous low-dose GM-CSF injections will also be administered subsequently. It is speculated that neoantigens released from the cryoablated necrotic cancer will be available in the vicinity of the 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, low-dose cyclophosphamide, and metronomic 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 AbscopalRx5001, 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.

Male or female subjects greater than 18 years of age with histologically- proven metastatic cancer with at least one imaging- or histologically- proven metastases to lymph nodes, bone, or soft tissue.

A Phase 2 Trial for Patients With Metastatic Solid Cancer

A Phase 2 Trial of Cryosurgical Freezing and Multiplex Immunochemotherapy in Patients With Metastatic Solid Cancer

rPFS as determined with both RECISTS1.1 and iRECIST criteria.

Incidence of adverse events will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

Each of the endpoints will be evaluated after stratifying for site of cancer origin, histologic type, and cancer grade (W.H.O. grading)

Efficacy of Cryosurgical Freezing and Multiplex Immunochemotherapy as determined by RECIST1.1 criteria

Rampart Health, L.L.C.

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Micronutrients

Hematinics

Vitamins

Pemetrexed

Vaccines

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

PDC\*lung01 Low Dose added to SoC, i.e., anti-PD-1 treatment

PDC\*lung01 High Dose added to SoC, i.e., anti-PD-1 treatment

PDC\*lung01 includes, in similar proportion, seven active agents, made of irradiated human plasmacytoid dendritic cells (PDC) loaded separately with a distinct synthetic peptide encoded by a lung tumor antigen, namely NY-ESO-1, MAGE-A3, MAGEA4, Multi-MAGE (an epitope common to several MAGE-A antigens), SURVIVN, MUC1 or a peptide derived from the Melan-A antigen.

PDC*lung01

The intention and decision to prescribe the anti-PD-1 monotherapy as SoC (TPS≥50%) must have been made by the investigator before and regardless of the patient's participation in the study.

For patients with non-squamous NSCLC included in Cohorts A1 and A2, maintenance by pemetrexed (IV every 3 weeks) can be administered according to SoC.

Alimta Injectable Product

Johan Vansteenkiste, Prof

PDC-LUNG-101 trial is an open-label, dose-escalation, phase I/II study to assess the safety, the tolerability, the immunogenicity and the preliminary clinical activity of the therapeutic cancer vaccine, PDC\*lung01, associated or not with anti-PD-1 treatment in patients with non-small-cell lung cancer.

The therapeutic cancer vaccine, PDC\*lung01 will be administered at two dose levels (low dose (LD) and high dose (HD)), as single agent or during maintenance treatment by pemetrexed (for adenocarcinomas in Cohorts A1 and A2) or added to the SoC (cohorts B1 and B2) i.e. anti-PD-1.

In cohorts A1 (low dose cohort) and A2 (high dose cohort), NSCLC patients will be treated at each of the six PDC\*lung01 treatment visits with low dose/high dose administered successively by subcutaneous and then by intravenous route.

In cohort B1 and B2, the first PDC\*lung01 injection will start within 48 hours after the first infusion of anti-PD-1. The fourth PDC\*lung01 injection will occur within 48 hours after the infusion of the second cycle of anti-PD-1.

For each patient, the study will be divided into three consecutive parts:

* Pre-screening (for HLA-A\*02:01 positivity), only patients with positive HLA-A\*02:01 status will be proposed to be screened.
* Active period comprising a screening period, a treatment period (visits V1 to V6, during which the patient receives PDC\*lung01 vaccine, at each visit), a V7 one week after the last injection and an end-of-treatment (EoT) visit (V8, 4 weeks after the last injection),
* Follow-up period which starts after the EoT visit and lasts up to two years after the first IMP administration.

Safety, Immunogenicity and Preliminary Clinical Activity Study of PDC*lung01 Cancer Vaccine in NSCLC

An Open-label, Dose-escalation, Phase I/II Study to Assess the Safety, the Tolerability, the Immunogenicity and the Preliminary Clinical Activity of the Therapeutic Cancer Vaccine, PDC*lung01, Associated or Not With Anti-PD-1 Treatment in Patients With Non-small-cell Lung Cancer (NSCLC)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Metastatic Solid Cancer Clinical Trial	NCT04739618	Metastatic Canc...	Keytruda Inject... Yervoy Injectab... GM-CSF Non-ablative Cr...	18 Years -	ImmunSYS, LLC
A Phase 2 Trial for Patients With Metastatic Solid Cancer	NCT04713371	Metastatic Canc...	Keytruda Inject... Yervoy Injectab... Cytoxan Cryosurgical fr... GM-CSF Injectab...	18 Years -	Rampart Health, L.L.C.
Safety, Immunogenicity and Preliminary Clinical Activity Study of PDC*lung01 Cancer Vaccine in NSCLC	NCT03970746	Non Small Cell ...	PDC*lung01 Keytruda Inject... Alimta Injectab...	18 Years -	PDC*line Pharma SAS
Safety, Immunogenicity and Preliminary Clinical Activity Study of PDC*lung01 Cancer Vaccine in NSCLC	NCT03970746	Non Small Cell ...	PDC*lung01 Keytruda Inject... Alimta Injectab...	18 Years -	PDC*line Pharma SAS
A Phase 2 Trial for Patients With Metastatic Solid Cancer	NCT04713371	Metastatic Canc...	Keytruda Inject... Yervoy Injectab... Cytoxan Cryosurgical fr... GM-CSF Injectab...	18 Years -	Rampart Health, L.L.C.
Safety, Immunogenicity and Preliminary Clinical Activity Study of PDC*lung01 Cancer Vaccine in NSCLC	NCT03970746	Non Small Cell ...	PDC*lung01 Keytruda Inject... Alimta Injectab...	18 Years -	PDC*line Pharma SAS
Metastatic Solid Cancer Clinical Trial	NCT04739618	Metastatic Canc...	Keytruda Inject... Yervoy Injectab... GM-CSF Non-ablative Cr...	18 Years -	ImmunSYS, LLC

Spots Global Cancer Trial Database for keytruda injectable product