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

NCT ID: NCT03567720

Last Updated: 2023-06-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

65 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-11

Study Completion Date

2024-09-30

Brief Summary

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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 along with treatment of an approved chemotherapy per standard of care (either nab-paclitaxel (Abraxane®) or gemcitabine (Gemzar®) plus carboplatin (Paraplatin®)) in participants with TNBC and no prior systemic therapy in the advanced or metastatic setting will be enrolled in this study.

Detailed Description

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The study will include a screening period, treatment period (up to 2 years), a long-term follow-up period, and a survival follow-up period. Participants will be followed for disease status and survival for up to a total duration of 5 years from the time of first dose of study treatment.

Eligible subjects with accessible lesions will be treated with TAVO-EP on Days 1, 5 and 8 every 6 weeks for up to 18 weeks. Pembrolizumab IV will be administered at a dose of 200 mg on Day 1 every 3-weeks for up to 35 cycles (Q3W) or 400 mg on Day 1 every 6 weeks for up to 18 cycles (Q6W).

Eligible subjects will be enrolled in one of the following cohorts.

* Cohort 1 is a single-arm study of intratumoral TAVO-EP and pembrolizumab (Q3W) in participants with TNBC and at least 1 line of prior systemic therapy in the advanced or metastatic setting.
* Cohort 2 is a single-arm study of intratumoral TAVO-EP and pembrolizumab along with treatment with an approved chemotherapy per standard of care (either nab-paclitaxel (Abraxane®)or gemcitabine (Gemzar®) plus carboplatin (Paraplatin®)) in participants with TNBC and no prior systemic therapy in the advanced or metastatic setting. Participants enrolled on or after Protocol Version 7 will have baseline disease PD-L1 negative status defined as Dako 22C3 assay CPS \<10.

For participants in Cohort 2 receiving nab-paclitaxel, the schedule for nab-paclitaxel is a separate 28-day cycle. The dosing regimen of nab-paclitaxel is 100 mg/m2 IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle.

For participants in Cohort 2 receiving gemcitabine plus carboplatin, the dosing regimen is gemcitabine 1000 mg/m² plus carboplatin area under the curve (AUC) 2 IV on Days 1 and 8 every 21 days.

Conditions

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Triple Negative Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Phase 2, Multi-Cohort, Open-Label, Multi-Center Study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TAVO-EP plus IV pembrolizumab

Intratumoral Tavokinogene Telseplasmid (tavo, pIL 12) plus Electroporation (ImmunoPulse) in Combination with Intravenous Pembrolizumab (Cohort enrollment completed)

Group Type EXPERIMENTAL

tavokinogene telseplasmid

Intervention Type BIOLOGICAL

Intratumoral tavokinogene telseplasmid delivered by electroporation every 6 weeks

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous 3 weekly treatments

Immunopulse

Intervention Type DEVICE

Device that administers electroporation

TAVO-EP plus IV pembrolizumab with chemotherapy

Intratumoral Tavokinogene Telseplasmid (tavo, pIL 12) plus Electroporation (ImmunoPulse) in Combination with Intravenous Pembrolizumab along with treatment of an approved chemotherapy per standard of care (either nab-paclitaxel or gemcitabine plus carboplatin)

Group Type EXPERIMENTAL

tavokinogene telseplasmid

Intervention Type BIOLOGICAL

Intratumoral tavokinogene telseplasmid delivered by electroporation every 6 weeks

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous 3 weekly treatments

Immunopulse

Intervention Type DEVICE

Device that administers electroporation

nab paclitaxel

Intervention Type DRUG

intravenous on days 1, 8 and 15 of each 28 day cycle

gemcitabine plus carboplatin

Intervention Type DRUG

intravenous on days 1 and 8 of every 21 days

Interventions

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tavokinogene telseplasmid

Intratumoral tavokinogene telseplasmid delivered by electroporation every 6 weeks

Intervention Type BIOLOGICAL

Pembrolizumab

Intravenous 3 weekly treatments

Intervention Type BIOLOGICAL

Immunopulse

Device that administers electroporation

Intervention Type DEVICE

nab paclitaxel

intravenous on days 1, 8 and 15 of each 28 day cycle

Intervention Type DRUG

gemcitabine plus carboplatin

intravenous on days 1 and 8 of every 21 days

Intervention Type DRUG

Other Intervention Names

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pIL-12 tavo-EP Keytruda tavo-EP Abraxane Gemzar Paraplatin

Eligibility Criteria

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Inclusion Criteria

1. Subjects with histologically confirmed diagnosis of inoperable locally advanced or metastatic TNBC.
2. The following prior cancer therapy requirements apply to specific cohorts:

1. For Cohort 1 only, subjects must have received at least 1 prior line of systemic chemotherapy or immunotherapy that includes an approved regimen.
2. For Cohort 2 only, subjects has had no prior systemic therapy in the advanced/metastatic setting and must not have progression or recurrence of disease within 6 months after the last dose of systemic neoadjuvant or adjuvant treatment, if applicable.
3. Subjects must have TNBC defined as estrogen (ER) receptor and progesterone (PR) receptor staining \<10% and human epidermal growth factor receptor 2 (HER2) - negative defined as immunohistochemistry (IHC) 0 to 1+
4. For Cohort 2, the participant must meet each of the following criteria:

1. Has baseline PD-L1 negative disease (defined as Dako 22C3 assay CPS\<10 \[or equivalent, per sponsor agreement\]) with results provided prior to start of study drug dosing: Historic results or new local PD-L1 testing from tissue collected within 6 months and without intervening therapy prior to Cycle 1 Day 1
2. Can provide a separate core or punch tumor biopsy collected at screening or archival tissue collected within 6 months (and without intervening therapy) prior to Cycle 1 Day 1
3. Has at least one lesion suitable for biopsy on Cycle 2 Day 1 (preferably same lesion from which the screening sample was collected).
5. Subjects must not have disease that, in the opinion of the Investigator, is considered amenable to potentially curative treatment.
6. Age ≥ 18 years of age of day of signing informed consent.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
8. Life expectancy of at least 6 months.
9. Participant has measurable disease based on RECIST v1.1 and has at least one identified lesion (target or non-target) that is accessible (up to 1.5 cm from the skin surface) and in a safe location for intratumoral injection and electroporation.
10. Demonstrate adequate organ function. All screening laboratories should be performed within 10 days of treatment initiation.
11. Female participant of childbearing potential must have a negative pregnancy test (for serum or urine pregnancy test, within 72 hours or 24 hours, respectively, 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.
12. Female participant of childbearing potential must be willing to use an adequate method of contraception from the first day of study treatment (or 14 days prior to the initiation of study treatment for oral contraception) and through at least 120 days following the last day of study treatment.
13. Male participant is surgically sterile OR agrees to use an adequate method of contraception when having sex with women of childbearing potential and refrains from sperm donation during the study treatment period and at least 120 days following the last day of study treatment.
14. Participant is 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. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
2. Subject has a clinically active brain metastases or leptomeningeal metastases. Participant who has a previously treated brain metastases or untreated asymptomatic brain metastases ≤5 mm may participate provided that they are radiologically stable (ie, without evidence of progression based on imaging during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to the first dose of study treatment.
3. Subject has had an allogenic tissue/solid organ transplant.
4. Subjects with electronic pacemakers or defibrillators.
5. Subject who have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
6. Subject has active hepatitis B (defined as HBsAg reactive) or active hepatitis C (defined as HCV RNA \[qualitative\] is detected). Note: Participant with a history of HBV or HCV controlled by ongoing viral suppression therapy is allowed.
7. 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.
8. Subject has an active autoimmune disease that required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
9. Subject has received a live-virus or live-attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Administration of killed vaccines are allowed.

Seasonal flu vaccines and COVID-19 vaccines that do not contain live virus (including attenuated vaccines) 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, participant has severe hypersensitivity (≥Grade 3) to or expected intolerance of the protocol-specified chemotherapy options. Participant must be able to tolerate at least one of the trial approved chemotherapy options.
12. Subject has received transfusion of blood products (including platelets or red blood cells) or colony stimulating factors (including G-CSF, GM-CSF, or recombinant erythropoietin) within 2 weeks prior to qualifying screening labs.
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. Participant has not recovered (ie, ≤Grade 1 or at baseline) from adverse events (AEs) due to a previously administered agent.
18. Subject has received any systemic anti-cancer agent or other local anti-cancer immunotherapy within 14 days prior to the start of study treatment.
19. Subject has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
20. Subject is 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

OncoSec Medical Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bridget O'Keeffe

Role: STUDY_DIRECTOR

OncoSec Medical Incorporated

Locations

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University of Arizona

Tucson, Arizona, United States

Site Status

UC San Diego

La Jolla, California, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

The Lundquist Institute

Torrance, California, United States

Site Status

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

University of Washington, Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Calvary Central Districts Hospital

Elizabeth Vale, South Australia, Australia

Site Status

Box Hill Hospital

Box Hill, Victoria, Australia

Site Status

Countries

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United States Australia

References

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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.

Reference Type DERIVED
PMID: 34754076 (View on PubMed)

Other Identifiers

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KEYNOTE-890

Identifier Type: OTHER

Identifier Source: secondary_id

MK3475-890

Identifier Type: OTHER

Identifier Source: secondary_id

OMS-I141 (KEYNOTE-890)

Identifier Type: -

Identifier Source: org_study_id

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