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Tavo and Pembrolizumab With or Without Chemotherapy in Patients With Inoperable Locally Advanced or Metastatic TNBC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03567720
Recruitment Status : Active, not recruiting
First Posted : June 26, 2018
Last Update Posted : June 12, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
OncoSec Medical Incorporated

Brief Summary:
This is a Phase 2, Multi-Cohort, Open-Label, Multi-Center Study. Cohort 1 will be a single-arm study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation (EP) in combination with pembrolizumab therapy. Cohort 2 will be a single-arm study of intratumoral tavo-EP plus pembrolizumab with nab-paclitaxel (Abraxane®) chemotherapy. Subjects with TNBC and EP accessible cutaneous / subcutaneous disease will be enrolled in this study.

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Biological: tavokinogene telseplasmid Biological: Pembrolizumab Device: Immunopulse Drug: nab paclitaxel Phase 2

Detailed Description:

The study will be comprised of a screening period, treatment period and a long-term follow-up.

Eligible subjects 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 up to 17 cycles of tavo-EP and 33 cycles of pembrolizumab from baseline (approximately 2 years) or until subsequent disease progression. For Cohort 2, subjects will be treated with an approved chemotherapy per standard of care, limited to nab-paclitaxel (Abraxane®). All accessible lesions, each ≥ 0.3 cm × 0.3 cm, may be treated; except where possible, 1 measurable lesion by RECIST (size ≥ 1.0 cm) should be selected and left untreated for the duration of the study.

Long-term Follow-up: All subjects will be followed after the End of Study (EOS) visit for Serious Adverse Events (SAEs) (through 90 days from the last dose of study drug) and long-term survival status for up to 1 year. EOS visit will occur 4 weeks after last study treatment administration.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase 2, Multi-Cohort, Open-Label, Multi-Center Study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multi-Cohort, Open-Label Study of Intratumoral Tavo Plus Electroporation in Combination With IV Pembrolizumab Therapy With or Without Chemotherapy in Patients With Inoperable Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)
Actual Study Start Date : October 11, 2018
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: tavo-EP plus IV pembrolizumab
Intratumoral Tavokinogene Telseplasmid (tavo, pIL 12) plus Electroporation (ImmunoPulse) in Combination with Intravenous Pembrolizumab (Cohort enrollment completed)
Biological: tavokinogene telseplasmid
Intratumoral tavokinogene telseplasmid delivered by electroporation every 6 weeks
Other Names:
  • pIL-12
  • tavo-EP

Biological: Pembrolizumab
Intravenous 3 weekly treatments
Other Name: Keytruda

Device: Immunopulse
Device that administers electroporation
Other Name: tavo-EP

Experimental: tavo-EP plus IV pembrolizumab with chemotherapy
Intratumoral Tavokinogene Telseplasmid (tavo, pIL 12) plus Electroporation (ImmunoPulse) in Combination with Intravenous Pembrolizumab and nab-paclitaxel chemotherapy
Biological: tavokinogene telseplasmid
Intratumoral tavokinogene telseplasmid delivered by electroporation every 6 weeks
Other Names:
  • pIL-12
  • tavo-EP

Biological: Pembrolizumab
Intravenous 3 weekly treatments
Other Name: Keytruda

Device: Immunopulse
Device that administers electroporation
Other Name: tavo-EP

Drug: nab paclitaxel
intravenous 4 weekly treatments
Other Name: Abraxane




Primary Outcome Measures :
  1. Cohort 1: Objective Response Rate (ORR) [ Time Frame: Approximately 2 years ]
    ORR by Investigator review based on RECIST v1.1

  2. Cohort 2: Objective Response Rate (ORR) [ Time Frame: Approximately 2 years ]
    ORR by Blinded Independent Central Review (BICR) based on RECIST v1.1


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Approximately 2 years ]
    Cohort 2: ORR by Investigator review based on RECIST v1.1

  2. Duration of Response (DOR) [ Time Frame: Approximately 2 years ]
    Cohort 1: PFS by Investigator based on RECIST v1.1; Cohort 2: Investigator and BICR based on RECIST v1.1

  3. Progression Free Survival (PFS) [ Time Frame: Approximately 2 years ]
    Cohort 1: PFS by Investigator based on RECIST v1.1; Cohort 2: Investigator and BICR review based on RECIST v1.1

  4. Immune Progression Free Survival (iPFS) [ Time Frame: Approximately 2 years ]
    Cohort 1: iPFS by Investigator review based on iRECIST; Cohort 2: Investigator and BICR based on iRECIST

  5. Immune Objective Response Rate (iORR) [ Time Frame: Approximately 2 years ]
    Cohort 1: iORR by Investigator review based on iRECIST; Cohort 2: Investigator and BICR based on iRECIST

  6. Disease Control Rate (DCR) [ Time Frame: Approximately 2 years ]
    Cohort 1: DCR by Investigator based on RECIST v1.1; Cohort 2: Investigator and BICR review based on RECIST v1.1

  7. Overall Survival [ Time Frame: Approximately 2 years ]
    Cohorts 1 and 2: Overall Survival for Cohorts



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects with histologically confirmed diagnosis of inoperable locally advanced or metastatic TNBC.
  2. For Cohort 1 only, subjects must have received at least 1 prior line of systemic chemotherapy or immunotherapy that includes an approved regimen.
  3. For Cohort 2 only, subjects may only have received neoadjuvant and adjuvant treatment in the non-metastatic or operable disease setting and must not have progressed within 6 months of last dose of (neo) adjuvant therapy.
  4. For both Cohorts 1 and 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+
  5. For Cohort 2 only, subjects must have PD-L1 testing per Dako 22C3 Combined Positive Score (CPS) assay performed prior to dosing. Prior testing will be acceptable if completed per required assay. Otherwise recent or newly obtained biopsy at screening will be collected for central determination of PD-L1 expression.
  6. Subjects must not have disease that, in the opinion of the Investigator, is considered amenable to potentially curative treatment.
  7. Age ≥ 18 years of age of day of signing informed consent.
  8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  9. Life expectancy of at least 6 months.
  10. 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).
  11. Demonstrate adequate organ function as defined below. All screening laboratories should be performed within 10 days of treatment initiation.
  12. For women of childbearing potential, negative serum or urine pregnancy test within 72 hours prior to the first study drug administration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  13. 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). Women may be surgically sterile or at least 1-year post-last menstrual period.
  14. 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.
  15. 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 central nervous system (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.
  3. For Cohort 2 only, less than 6-month disease free interval from the last dose of (neo)adjuvant therapy.
  4. Subject who had an allogenic tissue/solid organ transplant.
  5. Subjects with electronic pacemakers or defibrillators.
  6. Subject who have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  7. Subjects who are 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 hepatitis C virus (HCV) RNA results greater than the lower limits of detection of the assay.
  8. 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.
  9. 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.
  10. Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab or other anti-PD-1 monoclonal antibody therapy and/or any of its excipients.
  11. For Cohort 2 only: Subject has severe hypersensitivity (≥Grade 3) to nab-paclitaxel (Abraxane). Patient must be able to tolerate the trial approved chemotherapy.
  12. 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 3 weeks prior to study Cycle 1, Day 1 (Baseline).
  13. Subject has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  14. Subject has a history of interstitial lung disease.
  15. Subject has an active infection requiring systemic therapy.
  16. 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.
  17. Subject has not recovered (i.e., ≤ Grade 1 or at Baseline) from adverse events (AEs) due to a previously administered agent.
  18. Participation in another clinical study of an investigational anti-cancer agent or has used an investigational device within 30 days of screening.
  19. Subject has known psychiatric or substance abuse disorders that would interfere with the subject's ability to cooperate with the requirements of the study.
  20. Subjects who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the Screening visit through 120 days after the last dose of study treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03567720


Locations
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United States, California
Stanford University Medical Center
Palo Alto, California, United States, 94304
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Washington
University of Washington, Seattle Cancer Care Alliance
Seattle, Washington, United States, 98195
Australia, Queensland
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Calvary Central Districts Hospital
Elizabeth Vale, South Australia, Australia, 5112
Australia, Victoria
Box Hill Hospital
Box Hill, Victoria, Australia, 3128
Sponsors and Collaborators
OncoSec Medical Incorporated
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Kellie Malloy OncoSec Medical Incorporated
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Responsible Party: OncoSec Medical Incorporated
ClinicalTrials.gov Identifier: NCT03567720    
Other Study ID Numbers: OMS-I141 (KEYNOTE-890)
First Posted: June 26, 2018    Key Record Dates
Last Update Posted: June 12, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by OncoSec Medical Incorporated:
Metastatic
Inoperable Locally Advanced
TNBC
plasmid interleukin-12
tavokinogene telseplasmid
pembrolizumab
chemotherapy
pIL-12
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Pembrolizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological