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

NCT03567720 | Unknown Phase 2 DMC FDA Drug FDA Device

• 3 other identifiers: OMS-I141 (KEYNOTE-890)KEYNOTE-890MK3475-890
• Study Type: interventional
• Target: 65
• Locations: 2 countries
• Sites: 14

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 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.

Conditions

Triple Negative Breast Cancer

Keywords

Metastatic; Inoperable Locally Advanced; TNBC; plasmid interleukin-12; tavokinogene telseplasmid; pembrolizumab; chemotherapy; pIL-12; Nab-paclitaxel; gemcitabine plus carboplatin; IL-12; IL12

Outcome Measures

Primary Outcomes (2)

• Cohort 1: Objective Response Rate (ORR)

  ORR by Investigator review based on RECIST v1.1

  Approximately 2 years

• Cohort 2: Objective Response Rate (ORR)

  ORR by Investigator review based on RECIST v1.1

  Approximately 2 years

Secondary Outcomes (6)

• Duration of Response (DOR)

  Approximately 2 years

• Progression Free Survival (PFS)

  Approximately 2 years

• Immune Progression Free Survival (iPFS)

  Approximately 2 years

• Immune Objective Response Rate (iORR)

  Approximately 2 years

• Disease Control Rate (DCR)

  Approximately 2 years

Study Arms (2)

TAVO-EP plus IV pembrolizumab

EXPERIMENTAL

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

Biological: tavokinogene telseplasmid; Biological: Pembrolizumab; Device: Immunopulse

TAVO-EP plus IV pembrolizumab with chemotherapy

EXPERIMENTAL

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)

Biological: tavokinogene telseplasmid; Biological: Pembrolizumab; Device: Immunopulse; Drug: nab paclitaxel; Drug: gemcitabine plus carboplatin

Interventions

tavokinogene telseplasmid BIOLOGICAL

Intratumoral tavokinogene telseplasmid delivered by electroporation every 6 weeks

Also known as: pIL-12, tavo-EP

TAVO-EP plus IV pembrolizumab; TAVO-EP plus IV pembrolizumab with chemotherapy

Pembrolizumab BIOLOGICAL

Intravenous 3 weekly treatments

Also known as: Keytruda

TAVO-EP plus IV pembrolizumab; TAVO-EP plus IV pembrolizumab with chemotherapy

Immunopulse DEVICE

Device that administers electroporation

Also known as: tavo-EP

TAVO-EP plus IV pembrolizumab; TAVO-EP plus IV pembrolizumab with chemotherapy

nab paclitaxel DRUG

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

Also known as: Abraxane

TAVO-EP plus IV pembrolizumab with chemotherapy

gemcitabine plus carboplatin DRUG

intravenous on days 1 and 8 of every 21 days

Also known as: Gemzar, Paraplatin

TAVO-EP plus IV pembrolizumab with chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with histologically confirmed diagnosis of inoperable locally advanced or metastatic TNBC.
• The following prior cancer therapy requirements apply to specific cohorts:
• For Cohort 1 only, subjects must have received at least 1 prior line of systemic chemotherapy or immunotherapy that includes an approved regimen.
• 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.
• 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+
• For Cohort 2, the participant must meet each of the following criteria:
• 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
• 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
• Has at least one lesion suitable for biopsy on Cycle 2 Day 1 (preferably same lesion from which the screening sample was collected).
• Subjects must not have disease that, in the opinion of the Investigator, is considered amenable to potentially curative treatment.
• Age ≥ 18 years of age of day of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Life expectancy of at least 6 months.
• 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.
• Demonstrate adequate organ function. All screening laboratories should be performed within 10 days of treatment initiation.

You may not qualify if:

• 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.
• 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.
• Subject has had an allogenic tissue/solid organ transplant.
• Subjects with electronic pacemakers or defibrillators.
• Subject who have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• 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.
• 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.
• 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).
• 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.
• Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab or other anti-PD-1 monoclonal antibody therapy and/or any of its excipients.
• 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.
• 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.
• Subject has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Subject has a history of interstitial lung disease.

Sponsors & Collaborators

• OncoSec Medical Incorporated: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (14)

University of Arizona

Tucson, Arizona, 85719, United States

Location

UC San Diego

La Jolla, California, 92093, United States

Location

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

The Lundquist Institute

Torrance, California, 90502, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

University of Washington, Seattle Cancer Care Alliance

Seattle, Washington, 98195, United States

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Calvary Central Districts Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Related Publications (1)

• 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.

  PMID: 34754076 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Neoplasm Metastasis

Interventions

pembrolizumab; Taxes; Albumin-Bound Paclitaxel; Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes

Study Officials

• Bridget O'Keeffe

  OncoSec Medical Incorporated

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 2, Multi-Cohort, Open-Label, Multi-Center Study

Study Record Dates

• First Submitted: June 13, 2018
• First Posted: June 26, 2018
• Study Start: October 11, 2018
• Primary Completion: April 1, 2024
• Study Completion: September 1, 2024
• Last Updated: June 1, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); AU (4)