Clinical Trials /

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

NCT04526730

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Immunotherapy With Tavo + Electroporation in Combination With Nivo. in Melanoma Patients
  • Official Title: Neoadjuvant Immunotherapy With Intratumoral Tavokinogene Telseplasmid (Tavo) Plus Electroporation in Combination With Intravenous Nivolumab in Patients With Operable Locally- Regionally Advanced Melanoma

Clinical Trial IDs

  • ORG STUDY ID: MCC-20313
  • NCT ID: NCT04526730

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
TavoNeoadjuvant Treatment
NivolumabNeoadjuvant Treatment

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Neoadjuvant TreatmentExperimentalNeoadjuvant 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 1 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.
  • Tavo
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  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:

               1. Primary melanoma with clinically apparent regional lymph node metastases,
                  confirmed by pathological diagnosis.

               2. Clinically detected recurrence of melanoma at regional lymph node basin(s),
                  confirmed by pathological diagnosis.

               3. Clinically or histologically detected primary melanoma involving multiple
                  regional nodal groups, confirmed by pathological diagnosis.

               4. Clinically detected single site of nodal metastatic melanoma arising from an
                  unknown primary, confirmed by pathological diagnosis.

               5. 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.

               6. Participants with distant cutaneous/subcutaneous, soft tissue or nodal metastases
                  with or without regional lymph node involvement are allowed if they are
                  considered potentially surgically resectable and can be biopsied at Screening by
                  the treating surgical oncologist. Elevated LDH is not an exclusion.

          -  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:

               1. Accessible for electroporation

               2. Must be measured in at least one dimension (longest diameter in the plane of
                  measurement is to be recorded)

               3. 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.

          -  Male Participants: Male subjects of childbearing potential must be surgically sterile,
             or must agree to use adequate method of contraception during the study and at least 5
             months following the last day of study drug administration. Note: Abstinence is
             acceptable if this is the usual lifestyle and preferred contraception for the subject

          -  Female participants: Women of childbearing potential must have negative serum or urine
             pregnancy test within 72 hours prior to receiving the first study drug administration.
             If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
             test will be required. For women of childbearing potential, must be willing to use an
             adequate method of contraception from 30 days prior to the first study drug
             administration and 5 months following last day study drug administration (either tavo
             or nivolumab); acceptable methods include hormonal contraception (oral contraceptives
             - as long as on stable dose, patch, implant, and injection), intrauterine devices, or
             double barrier methods (e.g. vaginal diaphragm/vaginal sponge plus condom, or condom
             plus spermicidal jelly), sexual abstinence or a vasectomized partner. Women may be
             surgically sterile or at least 1-year post-last menstrual period. Note: Abstinence is
             acceptable if this is the usual lifestyle and preferred contraception for the subject.

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in this
             protocol

        Exclusion Criteria:

          -  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.

          -  Participation in another clinical study and systemic therapy within 30 days of Cycle
             1, Day 1.

          -  ECOG Performance Status: >1

          -  Inadequate organ function as defined per protocol

          -  Participant has severe hypersensitivity (≥Grade 3) to nivolumab and/or any of its
             excipients
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathological Complete Response
Time Frame:Up to 16 weeks after start of therapy
Safety Issue:
Description:Pathological Complete Response will be will be estimated based on the proportion of participants with 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.

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:12 weeks after start of therapy
Safety Issue:
Description:ORR assessed by Investigator based on RECIST v1.1 at 12 weeks during the Neoadjuvant phase
Measure:Relapse Free Survival
Time Frame:12 weeks after start of therapy
Safety Issue:
Description:RSF assessed by Investigator based on RECIST v1.1 at 12 weeks during the Neoadjuvant phase
Measure:Overall Survival
Time Frame:Up to 5 years after start of therapy
Safety Issue:
Description:Overall survival at 5 years after start of therapy
Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:Up to 5 years after start of therapy
Safety Issue:
Description:To determine the safety and tolerability of combined treatment as neoadjuvant therapy will be based on the frequency of AEs
Measure:Risk of Surgical Delay
Time Frame:Up to 16 weeks after start or therapy
Safety Issue:
Description:Definitive surgery will be planned at about 12 weeks. Participants will be monitored for surgical delay (either due to toxicity and/or tumor progression).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • Skin Cancer

Last Updated

August 25, 2020