Trial of pIL-12 Electroporation Malignant Melanoma

NCT01502293 | Completed Phase 2 Results DMC

• 2 other identifiers: OMS-I10011854
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

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

  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.

  Main Study: Screening and Days 90, 180, 270 and 360; Addendum: Screening and Weeks 12, 24, 36, and 48

Secondary Outcomes (7)

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

  From first administration of study treatment up to 30 days after last dose or until initiation of new anti-cancer treatment.

• Median Overall Survival (OS)

  From the start of study treatment until death, assessed up to 30 months.

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

  Main Study: Screening and Days 90, 180, 270 and 360; Addendum: Screening and Weeks 12, 24, 36, and 48

• Duration of Objective Response

  From first documented response until disease progression (Up to 29.7 months)

• Time to First Objective Response

  From start of study treatment until overall objective response (Up to 29.7 months)

Study Arms (3)

Main Study: tavo-EP

EXPERIMENTAL

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.

Biological: Tavokinogene Telseplasmid (tavo); Device: OncoSec Medical System (OMS)

Addendum: Regimen A tavo-EP

EXPERIMENTAL

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.

Biological: Tavokinogene Telseplasmid (tavo); Device: OncoSec Medical System (OMS)

Addendum: Regimen B tavo EP

EXPERIMENTAL

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.

Biological: Tavokinogene Telseplasmid (tavo); Device: OncoSec Medical System (OMS)

Interventions

Tavokinogene Telseplasmid (tavo) BIOLOGICAL

Patients received intratumoral injection(s) of tavo.

Also known as: interleukin-12 gene, IL-12 gene, pIL-12, plasmid DNA encoding human interleukin-12, plasmid IL-12 Device: OncoSec Med

Addendum: Regimen A tavo-EP; Addendum: Regimen B tavo EP; Main Study: tavo-EP

OncoSec Medical System (OMS) DEVICE

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.

Also known as: MedPulser

Addendum: Regimen A tavo-EP; Addendum: Regimen B tavo EP; Main Study: tavo-EP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced cutaneous or subcutaneous in-transit or metastatic melanoma (main and addendum)
• Age ≥ 18 years of age (main and addendum).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (main and addendum).
• Patients may have had prior chemotherapy or immunotherapy (vaccines, interferon, ipilimumab, or IL-2) with progression or persistent disease. All chemotherapy or immunotherapy (prior therapies for cancer per the addendum) must have been stopped 4 weeks prior to electroporation (main part) or prior to enrollment (addendum), unless the sponsor medical monitor approval was obtained.
• Patients may have had radiation therapy, but must have progressive disease after radiation therapy if the lesions to be treated are within the radiation field. Per the main study Protocol Amendment 10 (Version 11.0), dated 27 April 2016, all prior treatment toxicities had to be resolved to Grade 1. Per the study Addendum Amendment 5, dated 27 April 2016, all prior chemotherapy or immunotherapy treatment-related adverse events (AEs) must have been resolved to baseline or Grade 1 at the time of study enrollment; and all prior radiation treatment AEs must have been resolved to baseline at the time of study enrollment.
• Had a minimum of 2 eligible tumors and could have had up to 4 eligible tumors treated with electroporation (main part).
• Must have had a lesion at baseline eligible for treatment, meeting all of the following criteria: at least 0.3 cm x 0.3 cm in longest perpendicular diameters; and accessible for electroporation (addendum).
• Must have had at least 1 additional lesion that could have been followed for distant regression and that met all of the following criteria: must have remained untreated for duration of the study; and had longest perpendicular diameters at least 0.3 cm x 0.3 cm by clinical measurement; or at least 1.0 cm x 1.0 cm by computed tomography (CT) for non-nodal lesions; or at least 1.5 cm x 1.5 cm by CT for malignant lymph nodes (addendum).
• For women of childbearing potential, a negative serum or urine pregnancy test within 14 days to the first study drug administration, and use of birth control from 30 days prior to the first day of study drug administration and 30 days following last day study drug administration was required. Male patients must have been surgically sterile, or must have agreed to use contraception during the study and at least 30 days following the last day of study drug administration (addendum).
• Had a creatinine level \< 2 x upper limit of normal (ULN), and serum bilirubin within institutional normal limits obtained within 4 weeks prior to enrollment (main part and addendum).
• Had aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 1.5 x ULN within 4 weeks prior to enrollment (addendum).
• Had an absolute neutrophil count (ANC) \> 1000/mm and platelet count \> 100,000 /mm within 4 weeks prior to registration (main part) or enrollment (addendum).
• Were able to give informed consent and to follow guidelines given in the study (main part and addendum).

You may not qualify if:

• Prior therapy with IL-12 or prior gene therapy (main and addendum).
• Had an ECOG performance score of 3 or 4 (main part).
• Concurrent immunotherapy, chemotherapy, or radiation therapy for duration of patient participation on study (main part and addendum). For the study addendum, approved anti PD1 agents could have been permitted at the investigator's discretion and in consultation with the sponsor's medical monitor.
• Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study entry (main part) or enrollment (study addendum).
• Pregnant or breast-feeding women (main part and addendum).
• Women of childbearing age must have had a negative pregnancy test and had to be willing to use a highly effective method of contraception. Men who were sexually active must also have been willing to use an accepted and effective method of contraception (main part).
• Patients with electronic pacemakers or defibrillators are excluded from this study (main part and addendum).
• The patient is known to be positive for Human Immunodeficiency Virus (HIV) or has another confirmed or suspected immunosuppressive or immunodeficient condition (patients with thyroiditis are eligible) (addendum).
• Life expectancy of less than 6 months (main part and addendum).
• Had significant disease or uncontrolled disease, ie, cardiovascular renal, hepatic, endocrine, metabolic, neurologic, or other significant disease that could have limited the patient's ability to participate in the study as determined by the investigator or medical monitor (main part).
• History of significant cardiovascular disease (i.e. New York Heart Association (NYHA) class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias) (study addendum).
• Other clinically significant co-morbidities such as uncontrolled pulmonary disease, uncontrolled diabetes, active central nervous system (CNS) disease, active infection or any other condition that could compromise the patients participation in the study according to the investigator (study addendum).

Sponsors & Collaborators

• OncoSec Medical Incorporated: lead

Study Sites (6)

UCSF Helen Diller Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

University of Colorado Denver

Denver, Colorado, 80045, United States

Location

Lakeland Regional Cancer Center

Lakeland, Florida, 33805, United States

Location

St. Luke's University Health Network

Bethlehem, Pennsylvania, 18015, United States

Location

Seattle Cancer Care Alliance /University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Algazi A, Bhatia S, Agarwala S, Molina M, Lewis K, Faries M, Fong L, Levine LP, Franco M, Oglesby A, Ballesteros-Merino C, Bifulco CB, Fox BA, Bannavong D, Talia R, Browning E, Le MH, Pierce RH, Gargosky S, Tsai KK, Twitty C, Daud AI. Intratumoral delivery of tavokinogene telseplasmid yields systemic immune responses in metastatic melanoma patients. Ann Oncol. 2020 Apr;31(4):532-540. doi: 10.1016/j.annonc.2019.12.008. Epub 2020 Feb 1.

  PMID: 32147213 DERIVED

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

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

Results Point of Contact

• Title: Kellie Malloy, Chief Clinical Development Officer
• Organization: OncoSec Medical Incorporated

kmalloy@oncosec.com

858-375-9989

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2011
• First Posted: December 30, 2011
• Study Start: February 14, 2012
• Primary Completion: March 21, 2016
• Study Completion: March 21, 2016
• Last Updated: May 15, 2023
• Results First Posted: September 26, 2019

Record last verified: 2023-05

Locations

US (6)