Clinical Trials /

Intratumoral Tavo and Pembro in Patients With Inoperable Locally Advanced or Metastatic TNBC (KEYNOTE-890)

NCT03567720

Description:

This will be a Phase 2 study of intratumoral Tavokinogene Telseplasmid (tavo; pIL-12) Electroporation (EP) plus pembrolizumab. Subjects with TNBC and EP accessible cutaneous / subcutaneous disease will be enrolled in this study.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Intratumoral Tavo and Pembro in Patients With Inoperable Locally Advanced or Metastatic TNBC
  • Official Title: A Phase 2, Open-Label Study of Intratumoral Tavokinogene Telseplasmid Plus Electroporation in Combination With Intravenous Pembrolizumab Therapy in Patients With Inoperable Locally Advanced or Metastatic Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: OMS-I141
  • NCT ID: NCT03567720

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
tavokinogene telseplasmidpIL-12, tavo-EPintratumoral tavo-EP plus IV pembrolizumab
PembrolizumabKeytrudaintratumoral tavo-EP plus IV pembrolizumab

Purpose

This will be a Phase 2, Simon 2-stage minimax design, non-comparative, open-label, single-arm, multicenter study of intratumoral Tavokinogene Telseplasmid Plus Electroporation (tavo-EP) plus pembrolizumab therapy ("combined treatment"). Subjects with TNBC and EP accessible cutaneous / subcutaneous disease will be enrolled in this study.

Detailed Description

      The study will be comprised of a Core study (27 weeks), an Extension Phase and a long-term
      follow-up.

      Core Study: 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 (200 mg) on Day 1 of each
      3-week cycle for 24 weeks. As many accessible lesions, may be treated, as deemed feasible by
      the treating physician.

      Extension Phase: Patients who completed 27 weeks of treatment (Core study) with the
      investigators discretion, will enter an Extension phase and continue to receive the combined
      treatment of intratumoral tavo-EP and pembrolizumab for up to 35 cycles of pembrolizumab from
      baseline (approximately 2 years) or until subsequent disease progression.
    

Trial Arms

NameTypeDescriptionInterventions
intratumoral tavo-EP plus IV pembrolizumabExperimentalintratumoral tavo-EP plus IV pembrolizumab
  • tavokinogene telseplasmid
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects with histologically confirmed diagnosis of inoperable locally advanced or
             metastatic TNBC and at least 1 prior line of approved systemic chemotherapy or
             immunotherapy.

          2. Subjects must have estrogen (ER) receptor and progesterone (PR) receptor staining
             <10%, and be human epidermal growth factor receptor 2 (HER2)-negative defined as
             immunohistochemistry (IHC) 0 to 1+

          3. Subjects must not have disease that, in the opinion of the Investigator, is considered
             amenable to potentially curative treatment.

          4. Age ≥ 18 years of age of day of signing informed consent.

          5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

          6. Life expectancy of at least 6 months.

          7. Have measurable disease based on RECIST v1.1, and at least one anatomically distinct
             lesion involving skin or subcutaneous tissue accessible for electroporation of ≥ 0.3
             cm and lesion must be accurately measured in at least one dimension (longest diameter
             in the plane of measurement is to be recorded).

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

             - Absolute neutrophil count (ANC) ≥1.5 × 109/L; Platelets ≥100 × 109/L; Hemoglobin ≥9
             g/dL or ≥5.6 mmol/L*; Creatinine OR Measured or calculated** creatinine clearance
             (CrCl) Glomerular filtration rate (GFR) can also be used instead of creatinine or CrCl
             ≤1.5 × the upper limit of normal (ULN) OR > 60 mL/min for subject with creatinine
             levels >1.5 × institutional ULN; Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN
             for subjects with total bilirubin levels > 1.5× ULN; Aspartate aminotransferase (AST)
             and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN for subjects with liver
             metastases); International Normalized Ratio (INR) or Prothrombin Time (PT) and
             Activated Partial Thromboplastin Time (aPTT) ≤1.5 × ULN unless subject is receiving
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
             of anticoagulants

             * Criteria must be met without erythropoietin dependency and without packed red blood
             cell (pRBC) transfusion within last 2 weeks

             ** Creatinine clearance should be calculated per institutional standard.

          9. For women of childbearing potential, negative serum or urine pregnancy test within 72
             hours of to the first study drug administration, and 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).

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

         11. Able and willing to give informed consent and to follow study instructions.

        Exclusion Criteria:

          1. Subject has a known additional malignancy that is progressing or requires active
             treatment.

          2. Clinically active CNS metastases or any non-measurable bone-only 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.

          3. Subjects with electronic pacemakers or defibrillators.

          4. Subject who have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2
             antibodies).

          5. Subjects who have known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C
             (e.g., HCV RNA [qualitative] is detected).

          6. Subject has a diagnosis of immunodeficiency or is receiving chronic systemic steroid
             therapy (in dosing exceeding 10 mg/day of prednisone or 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.

          7. 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.

          8. Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab or other anti-PD-1
             monoclonal antibody therapy and/or any of its excipients.

          9. Subjects 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 3 weeks prior to study Cycle 1, Day 1
             (Baseline).

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

         11. Subject has a history of interstitial lung disease.

         12. Subject has an active infection requiring systemic therapy.

         13. 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.

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

         15. Participation in another clinical study of an investigational agent or has used an
             investigational device within 30 days of screening.

         16. Subjects who are pregnant or breastfeeding, 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:Objective Response Rate (ORR)
Time Frame:Approximately 2 years
Safety Issue:
Description:ORR by independent central review based on RECIST v1.1

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Within 24 weeks and approximately 2 years
Safety Issue:
Description:ORR by investigator review based on RECIST v1.1 and iRECIST
Measure:Duration of Response (DOR)
Time Frame:Within 24 weeks
Safety Issue:
Description:DOR by investigator independent central review based on RECIST v1.1 and iRECIST
Measure:Duration of Response (DOR)
Time Frame:Within 24 weeks and approximately 2 years
Safety Issue:
Description:DOR by investigator review based on RECIST v1.1 and iRECIST
Measure:Progression Free Survival (PFS)
Time Frame:Within 24 weeks
Safety Issue:
Description:PFS by independent central review based on RECIST v1.1 and iRECIST
Measure:Progression Free Survival (PFS)
Time Frame:Within 24 weeks and approximately 2 years
Safety Issue:
Description:PFS by investigator review based on RECIST v1.1 and iRECIST
Measure:Overall Survival
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

  • Metastatic
  • Inoperable Locally Advanced
  • TNBC
  • pIL-12
  • tavokinogene telseplasmid
  • pembrolizumab

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