Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Interleukin-12

Adjuvants, Immunologic

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Participants received tavo intratumorally followed immediately by electroporation (EP) on Days 1, 8, and 15 in a 6-week cycle for up to 9 cycles.

Patients received intratumoral injection(s) of tavo.

Tavokinogene Telseplasmid (tavo)

Electroporation via OMS was performed immediately following intratumoral injection of tavo. A sterile applicator containing 6 stainless steel electrodes arranged in a circle were placed around the tumor. The applicator was connected to the OMS power supply and six pulses were administered to each tumor lesion at the approximate point of tavo injection.

OncoSec Medical System (OMS)

This study will assess the safety and effectiveness of ImmunoPulse IL-12® in treatment-refractory metastatic and unresectable squamous cell carcinoma of the head and neck (HNSCC). ImmunPulseIL12® is the combination of intrtumoral interleukin-12 gene (also known as tavokinogene telseplasmid \[tavo\]) and in vivo electroporation-mediated plasmid deoxyribonucleic acid \[DNA\] vaccine therapy (tavo-EP) administered using the OncoSec Medical System (OMS). Intratumoral tavo is a gene therapy approach to directly induce a pro-inflammatory response within a tumor to initiate and/or enhance anti-tumor immunity.

Trial of pIL-12 Electroporation in Squamous Cell Carcinoma of the Head and Neck (IL12HNSCC)

A Multicenter Phase II Trial of Intratumoral pIL-12 Electroporation in Treatment-Refractory Metastatic and Unresectable SCC of the Head and Neck

BORR is defined as the percentage of participants with evaluable lesions that achieved a complete response (CR) or partial response (PR) as assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.

An AE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, medical treatment or procedure and which did not necessarily have to have had a causal relationship with this treatment. An adverse event could have, therefore, been any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, medical treatment or procedure whether or not considered related to the medicinal product. An SAE was defined an any untoward medical occurrence that at any dosage resulted in one or more of the following: death, A life-threatening adverse event (real risk of dying), inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly, required intervention to prevent permanent impairment of damage.

BORR is defined as the percentage of participants with evaluable lesions that achieved a complete response (CR) or partial response (PR) as assessed by the investigator using irRC criteria. CR: complete disappearance of all lesions (whether measurable or not) and the absence of new lesions for at least 4 weeks duration, confirmed by additional scan and visit 4 to 6 weeks after first documentation of CR. PR: ≥50% decrease in the product of the diameters from baseline.

The treated (injected, electroporated) lesion regression rate is defined as the percentage of patients who had at least one treated lesion that decreased in longest dimension by ≥ 30%. The untreated (non-injected, non-electroporated) lesion regression rate is defined as the percentage of patients who had at least one untreated lesion that decreased in longest dimension by ≥ 30%.

Progression free survival (PFS) time is defined as the duration between the date of treatment initiation (Study Day 1) to the first date of either disease progression at either local or any distant sites, or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients were censored at their date of last assessment, if they were alive and without evidence of disease progression.

TTP is defined as the number of days between the treatment initiation date (Study Day 1) and the earliest date of documented disease progression as defined by RECIST 1.1 or death that is not associated with prior disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Overall survival is defined as the time in days from the date of first study drug administration to the date of death.

OncoSec Medical Incorporated

Tavokinogene Telseplasmid (Tavo) Electroporation (EP)

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Sharron E Gargosky, Chief Clinical Regulatory Officer

Due to early termination of the study BORR by RECIST v1.1 data was not collected and reported.

Best Overall Response Rate (BORR) by RECIST v1.1

SAEs

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Due to early termination of the study BORR by irRC data was not collected and reported.

Best Overall Response Rate (BORR) by Immune-related Response Criteria (irRC)

Due to early termination of the study regression rate data was not collected and reported.

Regression Rate of Treated and Untreated Lesions

Due to early termination of the study PFS data was not collected and reported.

Median Progression Free Survival (PFS)

Due to early termination of the study TTP data was not collected and reported.

Median Time to Progression (TTP)

Due to early termination of the study overall survival data was not collected and reported.

Median Overall Survival (OS)

Overall Study

Infections

Symptoms and General Pathology

Rare Diseases

Carcinoma, Merkel Cell

Communicable Diseases

Polyomavirus Infections

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Merkel Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

Vaccines

Patients in Cohort A received one cycle (3 daily treatments on Days 1, 5, and 8) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, after which they proceeded to definitive treatment (surgery and/or radiation therapy) which started between 2 and 4 weeks after the first injection.

Patients in Cohort B received up to 4 cycles (3 daily treatments on Days 1, 5, and 8, per cycle) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, with 12 planned weeks between each cycle, lasting up to 12 months.

Shailender Bhatia

This phase II trial studies the effectiveness of ImmunoPulse IL-12® in treating patients with Merkel cell cancer. ImmunoPulse IL-12® is the combination of intratumoral interleukin-12 gene (also known as tavokinogene telseplasmid \[tavo\]) and in vivo electroporation-mediated plasmid deoxyribonucleic acid \[DNA\] vaccine therapy (tavo-EP) administered using the OncoSec Medical System (OMS). Placing the gene for interleukin-12 into Merkel cells may help the mount an effective anti-tumor immune response to kill tumor cells.

PRIMARY OBJECTIVES:

I. To measure the effect of intratumoral injection of tavo followed by in vivo electroporation (EP) (electroporation-mediated plasmid DNA vaccine therapy) on the local expression of interleukin-12 (IL-12) in the tumor microenvironment in patients with Merkel cell carcinoma (MCC).

SECONDARY OBJECTIVES:

I. To assess the safety of tavo-EP in MCC. II. To assess the clinical efficacy of this treatment approach in MCC. III. To assess the immunologic changes resulting from this treatment approach.

OUTLINE:

Patients receive tavo intratumorally (IT) and undergo electrical discharge via OMS around the tumor site for electroporation-mediated plasmid DNA vaccine therapy on days 1, 5, and 8. Patients with unresectable disease may receive a second course of treatment in 12 weeks. Patients with localized disease proceed to definitive treatment as determined by the treating physician starting 2-4 weeks after the first injection.

After completion of study treatment, patients are followed up at weeks 4-8 (for patients who received definitive treatment) or 12 (for patients with unresectable disease) and then annually for up to 5 years.

IL-12 Gene and in Vivo Electroporation-Mediated Plasmid DNA Vaccine Therapy in Patients With Merkel Cell Cancer

A Phase II Study of Intratumoral Injection of Interleukin-12 Plasmid and in Vivo Electroporation in Patients With Merkel Cell Carcinoma

The MAGPIX assay was used to assess differential expression of hIL-12 in patient tumor tissue before and after treatment with intratumoral (IT) tavo injections and in vivo electroporation (EP). Expression of hIL-12 was used to identify patients who met the primary endpoint of a 2-fold or higher increase in expression of hIL-12 in tumors after treatment. Fold change was taken as a comparison of hIL-12 expression at Week 3:pre-treatment, Week 6:pre-treatment, Week 8:pre-treatment, or Week 13:pre-treatment over baseline (pre- treatment). The fold change was calculated as log2 (time point/baseline).

ORR is defined as the percentage of participants with evaluable lesions that achieved a complete response (CR) or partial response (PR) as assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.

The same method was used to assess response rate for treated lesions and response rate for non-treated lesions. The best response rate for non-treated lesions was based on the number of patients who had at least one non-treated lesion.

Nanostring analysis was performed to determine the expression (mRNA) of IL-12. For each study patient, the fold change (log2 transformed) in IL-12A mRNA as measured by Nanostring was determined using the pre-treatment (screening) biopsy as a reference for the post treatment biopsy. A log2 fold change \>=1 is a positive result.

Local regression rate is defined as the percentage of participants with ≥30% regression (decrease in size) of at least one assessed local (injected) lesion.

Distant regression rate is defined as the percentage of participants with ≥30% regression (decrease in size) of at least one assessed distant (non-injected) lesion.

National Cancer Institute (NCI)

Cohort A: Tavo-EP

Patients in Cohort B received up to 4 cycles (3 daily treatments on Days 1, 5, and 8, per cycle) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, with 12 weeks planned between each cycle, lasting up to 12 months.

Cohort B: Tavo-EP

Total

Safety Analysis Set, all patients who received any amount of the study drug (tavo).

Efficacy Analysis Set, all patients from Cohort B who received any amount of the study drug (tavo).

Percentage of Participants Who Experienced At Least 2-Fold Increase in Expression of IL-12 Protein in the Tumor Tissue After Intratumoral (IT) pIL-12 Injections and In Vivo Electroporation

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Injected Lesions

Non-Injected Lesions

Efficacy Analysis Set, all patients from Cohort B who received any amount of the study drug (tavo) and had evaluable lesions.

Objective Response Rate (ORR) in Injected and Non-injected (Distant) Lesions

Efficacy Analysis Set, all patients from Cohort B who received any amount of the study drug (tavo) and had document disease progression.

Time to Progression (TTP)

Efficacy Analysis Set, all patients who received any amount of the study drug (tavo). Zero participants were analyzed for overall survival because all patients were alive at their study completion visit.

Overall Survival

Immunologic Effects of IT pIL-12 Injection and In Vivo EP Measured By: Percentage of Participants With a Positive Fold Change (Log2) in IL-12A Messenger Ribonucleic Acid (mRNA) for Patient Pre- and Post IT pIL 12 EP

All Patients: Tavo-EP

All patients from Cohorts A and B with evaluable lesions.

Local Regression Rate

Distant Regression Rate

Skin and Connective Tissue Diseases

Melanoma

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Patients received one cycle (3 daily treatments on Days 1, 5, and 8) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation. Treatment could be repeated at 3-month intervals until disease progression or unacceptable toxicity for up to 5 cycles.

Patients received one cycle (3 daily treatments on Days 1, 8, and 15) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation. Treatment could be repeated at 6-week intervals until disease progression or unacceptable toxicity for up to 9 cycles.

Patients received one cycle (3 daily treatments on Days 1, 5, and 8) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation. Treatment could be repeated at 6-week intervals until disease progression or unacceptable toxicity for up to 2 cycles.

This study will assess the safety and effectiveness of different dosing regimens of ImmunoPulse IL-12® in malignant melanoma. ImmunoPulse IL-12® is the combination of intratumoral interleukin-12 gene (also known as tavokinogene telseplasmid \[tavo\]) and in vivo electroporation-mediated plasmid deoxyribonucleic acid \[DNA\] vaccine therapy (tavo-EP) administered using the OncoSec Medical System (OMS). ImmunoPulse IL-12® is a gene therapy approach to directly induce a pro-inflammatory response within a tumor to initiate and/or enhance anti-tumor immunity.

Plasmid IL-12 (pIL-12) at a concentration of 0.5 mg/mL will be injected intratumorally at a dose volume of ¼ of the calculated lesion volume and a dose volume per lesion of 0.1 mL for lesions of volume \< 0.4 cm3. Six pulses at field strengths of (E+) of 1500 V/cm and pulse width of 100 μs at 1-second intervals will be administered using the OncoSec Medical System (OMS) to each previously injected tumor.

Three treatment regimens will be explored:

Main Study: Treatment on Days 1, 5 and 8 for 1 cycle. Additional cycles may be repeated every 3 months at the Investigator's discretion.

Addendum Regimen A: Treatment on Days 1, 8 and 15 every 6 weeks. Subsequent cycles may be given at 6-week intervals, for up to 9 treatment cycles in total.

Addendum Regimen B: Treatment on Days 1, 5 and 8 every 6 weeks. Subsequent cycles may be given at 6-week intervals, for up to 9 treatment cycles in total.

NOTE: An Addendum was added to the Main Protocol with the purpose of exploring the safety and efficacy of an increased treatment frequency schedule.

Trial of pIL-12 Electroporation Malignant Melanoma

A Multicenter Phase II Trial of Intratumoral pIL-12 Electroporation in Advanced Stage Cutaneous and in Transit Malignant Melanoma

ORR is defined as the percentage of participants with evaluable lesions that achieved a complete response (CR) or partial response (PR) as assessed by the investigator using Modified "Skin" Response Evaluation Criteria In Solid Tumors (RECIST). CR: complete disappearance of all lesions (whether measurable or not) and the absence of new lesions for at least 4 weeks duration, confirmed by additional scan and visit 4 to 6 weeks after first documentation of CR. PR: ≥30% decrease in longest dimension (LD) from baseline lesion, and no new lesions.

Overall survival (OS) time is defined as the duration between the date of treatment initiation (Study Day 1) to the date of death, regardless of the cause of death, assessed up to 30 months.

ORR is defined as the percentage of participants with evaluable lesions that achieved a complete response (CR) or partial response (PR) as assessed by the investigator using irRC criteria. CR: complete disappearance of all lesions (whether measurable or not) and the absence of new lesions for at least 4 weeks duration, confirmed by additional scan and visit 4 to 6 weeks after first documentation of CR. PR: ≥50% decrease in the product of the diameters from baseline.

Duration of objective response (CR or PR based on Modified RECIST criteria) is defined as the number of days from the initial documentation of an objective response to the most current evaluation of that response or to documentation of progression or death associated with disease progression. CR: complete disappearance of all lesions (whether measurable or not) and the absence of new lesions for at least 4 weeks duration, confirmed by additional scan and visit 4 to 6 weeks after first documentation of CR. PR: ≥30% decrease in longest dimension (LD) from baseline lesion, and no new lesions. Patients who had an initial response and did not progress were censored at their date of last assessment.

Time to objective response (CR or PR based on Modified RECIST criteria) is defined as the number of days between the date of treatment initiation (Study Day 1) to the first date of the first documentation of an objective response. CR: complete disappearance of all lesions (whether measurable or not) and the absence of new lesions for at least 4 weeks duration, confirmed by additional scan and visit 4 to 6 weeks after first documentation of CR. PR: ≥30% decrease in longest dimension (LD) from baseline lesion, and no new lesions. Patients who had an initial response and did not progress were censored at their date of last assessment. Patients who did not have an objective response were censored at their date of last assessment.

Progression free survival (PFS) is defined as the duration between the date of treatment initiation (Study Day 1) to the first date of either disease progression at either local or distant sites, or death from any cause. Disease progression at local or distant lesions is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Patients were censored at their last assessment date if there was no evidence of disease progression.

Main Study: Tavo-EP

Addendum: Regimen A Tavo-EP

Addendum: Regimen B Tavo-EP

Safety Analysis Set, all patients who were enrolled and received any amount of the study treatment (pIL-12).

An Addendum was added to the Main Protocol with the purpose of exploring the safety and efficacy of an increased treatment frequency schedule.

Kellie Malloy, Chief Clinical Development Officer

Efficacy Analysis Set, all enrolled patients who received at least one full cycle of study treatment and had at least one efficacy assessment following the first dose of study drug, who had at least one post-baseline response assessment.

Best Overall Objective Response Rate (ORR) by Modified "Skin" RECIST

Addendum: Regimen B

Addendum: Regimen A

Efficacy Analysis Set, all enrolled patients who received at least one full cycle of study treatment and had at least one efficacy assessment following the first dose of study drug. Patients were censored at the last date that they were known to be alive.

Objective Response Rate (ORR) by Immune Related Response Criteria (irRC)

Efficacy Analysis Set, all enrolled patients who received at least one full cycle of study treatment and had at least one efficacy assessment following the first dose of study drug, who had at least one post-baseline response assessment and had a CR or PR.

Duration of Objective Response

Patients received cycle (3 daily treatments on Days 1, 5, and 8) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation. Treatment could be repeated at 6-week intervals until disease progression or unacceptable toxicity for up to 2 cycles.

Time to First Objective Response

Efficacy Analysis Set, all enrolled patients who received at least one full cycle of study treatment and had at least one efficacy assessment following the first dose of study drug, who had at least one post-baseline response assessment and had a CR or PR based on Modified RECIST criteria.

Median Progression Free Survival

Treated

Untreated

Efficacy Analysis Set, all enrolled patients who received at least one full cycle of study treatment and had at least one efficacy assessment following the first dose of study drug.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of pIL-12 Electroporation in Squamous Cell Carcinoma of the Head and Neck (IL12HNSCC)	NCT02345330	Head and Neck S...	Tavokinogene Te... OncoSec Medical...	18 Years -	OncoSec Medical Incorporated
IL-12 Gene and in Vivo Electroporation-Mediated Plasmid DNA Vaccine Therapy in Patients With Merkel Cell Cancer	NCT01440816	Merkel Cell Car...	Tavokinogene Te... OncoSec Medical...	18 Years -	OncoSec Medical Incorporated
Trial of pIL-12 Electroporation Malignant Melanoma	NCT01502293	Melanoma	Tavokinogene Te... OncoSec Medical...	18 Years -	OncoSec Medical Incorporated
IL-12 Gene and in Vivo Electroporation-Mediated Plasmid DNA Vaccine Therapy in Patients With Merkel Cell Cancer	NCT01440816	Merkel Cell Car...	Tavokinogene Te... OncoSec Medical...	18 Years -	OncoSec Medical Incorporated

Spots Global Cancer Trial Database for tavokinogene telseplasmid (tavo)