Clinical Trials /

Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Pembrolizumab or Nivolumab Treatment

NCT03132675

Description:

Keynote 695 will be a Phase 2 study of intratumoral tavokinogene telseplasmid (tavo; pIL-12) Electroporation (EP) plus IV Pembrolizumab. Eligible patients will be those with pathological diagnosis of unresectable or metastatic melanoma who are progressing or have progressed on pembrolizumab or nivolumab.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Pembrolizumab or Nivolumab Treatment
  • Official Title: A Multicenter Phase 2, Open Label Study of Intratumoral Tavo Plus Electroporation in Combination With Intravenous Pembrolizumab in Patients With Stage III/IV Melanoma Who Are Progressing on Either Pembrolizumab or Nivolumab Treatment

Clinical Trial IDs

  • ORG STUDY ID: OMS-I103 (KEYNOTE 695)
  • NCT ID: NCT03132675

Conditions

  • Stage III/IV Melanoma

Interventions

DrugSynonymsArms
tavokinogene telseplasmidpIL-12, tavo-EPtavo-EP plus IV pembrolizumab
PembrolizumabKeytrudatavo-EP plus IV pembrolizumab

Purpose

This will be a Phase 2 study of intratumoral tavokinogene telseplasmid (tavo; pIL-12) Electroporation (EP) plus IV Pembrolizumab. Eligible patients will be those with pathological diagnosis of unresectable or metastatic melanoma who are progressing or have progressed on pembrolizumab or nivolumab.

Detailed Description

      The study will be comprised of a screening period, a treatment period (up to 2 years) and a
      long term follow-up.

      Eligible patients will be treated with intratumoral tavo-EP to the accessible lesions on Days
      1, 5 and 8 every 6 weeks and with IV pembrolizumab (200mg) on Day 1 of each 3-week cycle for
      17 tavo-EP cycles and 33 pembrolizumab cycles (from baseline) of continued treatment
      (approximately 2 years), or until disease progression. As many accessible lesions may be
      treated as deemed feasible by the treating physician assuming the size of each lesion is
      greater than 0.3 cm x 0.3 cm.

      Long-term Follow-up: All subjects will be followed after End of Study (EOS) visit for SAEs
      (through 90 days from last dose of study drug) and long term survival status. EOS visit will
      occur 4 weeks after last study treatment administration.
    

Trial Arms

NameTypeDescriptionInterventions
tavo-EP plus IV pembrolizumabExperimentalIntratumoral Tavokinogene Telseplasmid (tavo, pIL 12) plus Electroporation (ImmunoPulse) in Combination with Intravenous Pembrolizumab
  • tavokinogene telseplasmid
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

        In order to be eligible for participation in this study, the subject must meet all of the
        following:

          1. Pathologically documented unresectable melanoma, American Joint Committee on Cancer
             (AJCC) version 8, Stage III or IV. Subjects must have histological or cytological
             confirmed diagnosis of unresectable melanoma with progressive locally advanced or
             metastatic disease.

          2. Subjects must be refractory to anti PD 1 monoclonal antibodies (mAb) (pembrolizumab or
             nivolumab either as monotherapy or in combination with other approved checkpoint
             inhibitors or targeted therapies according to their approved label) and subjects must
             meet all of the following criteria:

               1. Received treatment of FDA-approved anti PD1 mAb (dosed per label of the country
                  providing the clinical site) for at least 12 weeks.

               2. Progressive disease after anti PD1 mAb will be defined according to RECIST v1.1.
                  The initial evidence of PD is to be confirmed by a second assessment, no less
                  than 4 weeks from the date of the first documented PD, in the absence of rapid
                  clinical progression. (This determination is made by the Investigator; the
                  Sponsor will collect imaging scans for retrospective analysis. Once PD is
                  confirmed, the initial date of PD documentation will be considered the date of
                  disease progression).

               3. Documented disease progression within 12 weeks of the last dose of anti PD1 mAb.
                  Subjects who were re treated with anti PD1 mAb and subjects who were on
                  maintenance with anti PD1 mAb will be allowed to enter the study as long as there
                  is documented PD within 12 weeks of the last treatment date (with anti PD1 mAb).

          3. Resolution/improvement of anti PD1 mAb related AEs (including immune related AEs;
             irAEs) back to Grade 0 1 and ≤10 mg/day prednisone (or equivalent dose) for irAEs for
             at least 2 weeks prior to the first dose of study drug:

               1. No history of common toxicity criteria adverse events (CTCAE) Grade 4 irAEs from
                  anti PD1 mAb.

               2. No history of CTCAE Grade 3 requiring steroid treatment (>10 mg/day prednisone or
                  equivalent dose) for >12 weeks or CTCAE Grade 2 pneumonitis regardless of steroid
                  treatment.

               3. Minimum of 4 weeks (washout period) from the last dose of anti PD1 mAb

          4. Prior treatment with an approved BRAF inhibitor if BRAF V600 mutation positive.

          5. Age ≥ 18 years of age on day of signing informed consent.

          6. Has a performance status of 0 or 1 on the ECOG Performance Scale, collected within 7
             days of initial treatment.

          7. 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 accurately measured in at least one dimension (longest diameter in the
                  plane of measurement is to be recorded Note: Tumor lesions situated in a
                  previously irradiated area are considered measurable if progression has been
                  demonstrated in such lesions

          8. Demonstrate adequate organ function. All screening laboratories should be performed
             within 10 days of treatment initiation.

          9. 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.

         10. 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 120 days
             following last day study drug administration (either tavo or pembrolizumab).
             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.

         11. Male subjects must be surgically sterile or must agree to use adequate method of
             contraception during the study and at least 120 days following the last day of study
             drug administration.

         12. Able and willing to provide written informed consent and to follow study instructions.

        Exclusion Criteria:

          1. Subject has disease that is suitable for local therapy administered with curative
             intent.

          2. Subject with a diagnosis of uveal or mucosal melanoma.

          3. Subject has a known additional malignancy that is progressing or requires active
             treatment within the past 3 years. 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.

          4. Clinically active CNS metastases. Subjects with previously treated brain metastases
             may participate provided they are radiologically stable, i.e., without evidence of
             progression for at least 4 weeks by repeat imaging (note that the repeat imaging
             should be performed during study screening), clinically stable and without requirement
             of steroid treatment for at least 14 days prior to first dose of study drug.

          5. Greater than 3 visceral sites of metastases (this does not include nodal metastases
             associated with visceral organs)

          6. Subjects with stage IVc melanoma with liver or bowel metastases.

          7. Subject who had an allogenic tissue/solid organ transplant.

          8. Subjects with electronic pacemakers or defibrillators.

          9. Subjects who have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2
             antibodies). HIV-infected subjects with a history of Kaposi sarcoma and/or
             Multicentric Castleman Disease.

         10. Subjects who have history of Hepatitis B or C infections or known to be positive for
             Hepatitis B antigen (HBsAg) or Hepatitis B virus (HBV) DNA or Hepatitis C antibody or
             RNA. Active Hepatitis C is defined by a known positive Hep C Ab result and known
             quantitative HCV RNA results greater than the lower limits of detection of the assay

         11. Subject has a diagnosis of immunodeficiency or is receiving chronic systemic steroid
             therapy (in dosing exceeding 10 mg daily of prednisone equivalent) 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 Sponsor.

         12. Subjects 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.

         13. Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
             excipients.

         14. Subjects who have received transfusion of blood products (including platelets or red
             blood cells) or colony stimulating factors (including G CSF, GM CSF or recombinant
             erythropoietin) within 4 weeks prior to study Cycle 1, Day 1 (baseline).

         15. Subject has a history of (non infectious) pneumonitis that required steroids or
             current pneumonitis.

         16. Subject has a history of interstitial lung disease.

         17. Subject has an active infection requiring systemic therapy.

         18. Subject has a history or current evidence of any condition, therapy, or laboratory
             abnormality that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating Investigator.

         19. Subject has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to
             a previously administered agent.

         20. Participation in another clinical study of an investigational anti-cancer agent or has
             used an investigational device within 30 days of screening.

         21. Subjects who have had intervening therapy following confirmed progression on anti PD 1
             therapy or anti-PD-1 combination therapy with the exception of approved BRAF/MEK
             inhibitor combinations. PD-1 combination therapy is acceptable as the last prior
             treatment and may include anti- PD-1 anti-CTLA4 antibody combination therapy and
             anti-PD-1 combinations with investigational or injectable therapy.

         22. Subject has known psychiatric or substance abuse disorder that would interfere with
             the subject's ability to cooperate with the requirements of the study.

         23. Subjects who are pregnant or breast-feeding or expecting to conceive or father
             children within the projected duration of the study, starting with the screening visit
             through 120 days after the last dose of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:approximately 2 years
Safety Issue:
Description:ORR by blinded independent central review (BICR) based on RECIST v1.1

Secondary Outcome Measures

Measure:Objective Response rate (ORR)
Time Frame:approximately 2 years
Safety Issue:
Description:ORR by investigator assessment based on RECIST v1.1
Measure:Duration of Response (DOR)
Time Frame:approximately 2 years
Safety Issue:
Description:DOR by Investigator assessment and BICR based on RECIST v1.1
Measure:Progression free survival (PFS)
Time Frame:approximately 2 years
Safety Issue:
Description:PFS by investigator assessment and BICR based on RECIST v1.1
Measure:Immune Progression Free Survival (iPFS)
Time Frame:approximately 2 years
Safety Issue:
Description:iPFS by Investigator assessment and BICR based on iRECIST
Measure:Immune Overall Response Rate (iORR)
Time Frame:approximately 2 years
Safety Issue:
Description:iORR by Investigator assessment and BICR based on iRECIST
Measure:Overall survival (OS)
Time Frame:approximately 2 years
Safety Issue:
Description:Overall survival

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:OncoSec Medical Incorporated

Trial Keywords

  • Melanoma
  • pIL-12
  • pembrolizumab
  • tavokinogene telseplasmid

Last Updated