Neoadjuvant Immunotherapy With Tavo + Electroporation in Combination With Nivo. in Melanoma Patients

NCT04526730 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: MCC-20313
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2 open-label, single-arm study of neoadjuvant treatment of intratumoral tavo-EP plus nivolumab IV infusion. Eligible participants will be those with pathological diagnosis of operable locally-regionally advanced melanoma.

Conditions

Melanoma

Keywords

Skin Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response

  For each subject, the study intervention consists of 3 phases: (1) Neoadjuvant Phase; (2) Surgery Phase; (3) Adjuvant Phase. Completion of all 3 phases is required for primary completion of the study. The study protocol requires that all subjects will be followed for 4 weeks after last dose of nivolumab at End of Study (EOS) visit. That is 4 weeks after the conclusion of the adjuvant phase. For the purpose of reporting the primary outcome measure, Pathologic Complete Response will be estimated based on the proportion of participants who have completed the study phases and were found to have no viable tumor on histologic assessment at definitive surgery after the 12- week Neoadjuvant phase. Surgery will then be scheduled 2-4 weeks after neoadjuvant phase. This will be followed by the adjuvant phase. Therefore, the proportion of participants who continue in Pathologic Complete Response following completion of the 3 study phases would be reported.

  At least four weeks after the last dose of nivolumab at End of Study (EOS) visit

Secondary Outcomes (5)

• Objective Response Rate

  Conclusion of the neoadjuvant phase.

• Relapse Free Survival

  At least four weeks after the last dose of nivolumab at End of Study (EOS) visit

• Overall Survival

  At 1 year after start of therapy

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Up to 5 years after start of therapy

• Risk of Surgical Delay

  Up to 16 weeks after start or therapy

Study Arms (1)

Neoadjuvant Treatment

EXPERIMENTAL

Neoadjuvant Phase: (3 x 4-week cycles, total 12 weeks): At every cycle, intratumoral tavo-EP will be administered (on Days 1 and 8) concurrently with 480 mg nivolumab IV infusion on Day 8 of each cycle (tavo-EP will be administered prior to nivolumab infusion). Definitive Surgery Phase: Surgery may be scheduled about 2-4 weeks after the last dose of nivolumab following radiologic and clinical assessment at that point. Pathologic response will be determined by institutional pathologist. Adjuvant Phase: Adjuvant therapy with nivolumab monotherapy will begin approximately 2-4 weeks following definitive surgery; recovery from surgery is required (Day 1 of Cycle 4 will be determined by the treating investigator once the subject is cleared to initiate systemic therapy). Nivolumab (480 mg IV infusion on Day 1 of each 4-week cycle) will be administered for up to 9 cycles during the Adjuvant phase.

Drug: Tavo; Drug: Nivolumab; Device: OncoSec Medical Electroporation Therapy System

Interventions

Tavo DRUG

Tavo will be injected on Days 1 and 8 every 4 weeks at a dose volume of ¼ of the calculated lesion volume with a minimum dose volume per lesion of 0.1 mL for lesions of volume \<0.4 cm3

Neoadjuvant Treatment

Nivolumab DRUG

Nivolumab will be administered 480 mg every 4 weeks over 30 minute infusions

Neoadjuvant Treatment

OncoSec Medical Electroporation Therapy System DEVICE

The OMS (OncoSec Medical Electroporation Therapy System), a medical EP device system, consists of 3 components: 1. an Electroporation Generator that generates electric pulses, 2. a sterile Applicator Tip containing needle array, and 3. an Applicator Handle that connects to the Electroporation Generator at the proximal end and connects to the Applicator Tip at the distal end. Upon user activation of the attached Foot Switch, the OMS Electroporation Generator delivers controlled electrical pulses in a square wave pulse pattern yielding optimal transmembrane potential for electroporation to occur. EP pulses occur between 6 hexagonal opposing needle electrodes. After the first pulse, the polarity between the opposing needle electrode pairs is reversed and the needle pair is pulsed again. After the initial paired pulse, the pulse delivery is rotated clockwise to the next opposing needle pairs until a total of 6 pulses are delivered to complete the EP sequence.

Also known as: Electroporation

Neoadjuvant Treatment

Eligibility Criteria

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

You may qualify if:

• Participant must be ≥ 18 years of age inclusive, at the time of signing the informed consent
• Histologic diagnosis of melanoma
• Must be considered surgically operable and may present as any of the following groups:
• Primary melanoma with clinically apparent regional lymph node metastases, confirmed by pathological diagnosis.
• Clinically detected recurrence of melanoma at regional lymph node basin(s), confirmed by pathological diagnosis.
• Clinically or histologically detected primary melanoma involving multiple regional nodal groups, confirmed by pathological diagnosis.
• Clinically detected single site of nodal metastatic melanoma arising from an unknown primary, confirmed by pathological diagnosis.
• Participants with in transit or satellite metastases with or without lymph node involvement are allowed if they are considered surgically resectable at Screening by the treating surgical oncologist.
• Participants are eligible for this study either at presentation for primary melanoma with concurrent regional nodal and/or in-transit or distant metastasis, or at the time of clinically detected nodal, in transit, or distant recurrence
• Participants must be evaluated by standard-of-care full body imaging studies including positron emission tomography - computed tomography (PET-CT ;preferred; including diagnostic CT component if possible) or CT (if PET-CT cannot be done) as well as magnetic resonance imaging (MRI) of the brain (or CT if MRI cannot be done) as part of the initial clinical work-up at Screening (no more than 4 weeks prior to Cycle 1, Day 1).
• Have measurable disease based on RECIST v1.1, with at least one anatomically distinct lesion. Lesion or lesions must meet all the following baseline criteria:
• Accessible for electroporation
• Must be measured in at least one dimension (longest diameter in the plane of measurement is to be recorded)
• Greater than 3 mm
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

You may not qualify if:

• Participant has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Also, includes patients who are considered disease-free for at least 3 years from the last definitive treatment for a second malignancy.
• Participants who have Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies at Screening). HIV testing at screening is not required unless considered clinically indicated by the treating physician.
• Participants who have active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected at Screening); Note: Participants who have been vaccinated against Hepatitis B and who are positive only for the Hepatitis B surface antibody are permitted to participate in the study. Hepatitis B and C testing at screening is not required unless considered clinically indicated by the treating physician.
• Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. The use of physiologic doses of corticosteroids may be approved after consultation with the Principal Investigator.
• Participant has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Participant has a history of interstitial lung disease.
• Participant has an active infection requiring systemic therapy.
• Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Participant has not recovered (i.e., \> Grade 1 at Cycle 1, Day 1) from AEs due to a previously administered agent.
• Participant has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Participants who are pregnant or breast feeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 5 months after the last dose of trial treatment.
• Participants with electronic pacemakers or defibrillators
• Participants who have received a live-virus vaccination within 30 days of the first dose of treatment. Seasonal flu vaccines that do not contain live virus are permitted
• Participants who have received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to study Cycle 1, Day 1.
• Previous treatment with anti-PD1 or anti-PDL1 immunotherapy.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• OncoSec Medical Incorporated: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Publications (2)

• Tarhini AA, Eroglu Z, Eljilany I, Zager JS, Gonzalez RJ, Sarnaik AA, Cruse CW, Khushalani NI, De Aquino DB, Abraham E, Acevedo DM, Richards A, Schell MJ, Kalos D, Chen PL, Messina JL, Canton DA, Sondak VK. Neoadjuvant Intratumoral Plasmid IL-12 Electro-Gene-Transfer and Nivolumab in Patients with Operable, Locoregionally Advanced Melanoma. Clin Cancer Res. 2024 Dec 2;30(23):5333-5341. doi: 10.1158/1078-0432.CCR-24-2768.

  PMID: 39417680 RESULT

• Jacobs L, Yshii L, Junius S, Geukens N, Liston A, Hollevoet K, Declerck P. Intratumoral DNA-based delivery of checkpoint-inhibiting antibodies and interleukin 12 triggers T cell infiltration and anti-tumor response. Cancer Gene Ther. 2022 Jul;29(7):984-992. doi: 10.1038/s41417-021-00403-8. Epub 2021 Nov 9.

  PMID: 34754076 DERIVED

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

Nivolumab; Electroporation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques

Results Point of Contact

• Title: Ahmad Tarhini, MD, PhD
• Organization: Moffitt Cancer Center

Ahmad.Tarhini@moffitt.org

813-745-8581

Study Officials

• Ahmad Tarhini, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: August 26, 2020
• Study Start: December 22, 2020
• Primary Completion: March 26, 2024
• Study Completion: May 22, 2025
• Last Updated: February 20, 2026
• Results First Posted: May 6, 2025

Record last verified: 2026-02

Locations

US (1)