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

NCT03132675 | Unknown Phase 2 DMC FDA Drug FDA Device

• 3 other identifiers: OMS-I103 (KEYNOTE 695)Keynote-695MK3475-695
• Study Type: interventional
• Target: 143
• Locations: 5 countries
• Sites: 33

Brief Summary

Keynote 695 is 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 either pembrolizumab or nivolumab.

Conditions

Stage III/IV Melanoma

Keywords

Melanoma; pIL-12; pembrolizumab; tavokinogene telseplasmid; Keynote 695; IL-12; IL12; plasmid interleukin-12

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR by blinded independent central review (BICR) based on RECIST v1.1

  approximately 2 years

Secondary Outcomes (6)

• Objective Response rate (ORR)

  approximately 2 years

• Duration of Response (DOR)

  approximately 2 years

• Progression free survival (PFS)

  approximately 2 years

• Immune Progression Free Survival (iPFS)

  approximately 2 years

• Immune Overall Response Rate (iORR)

  approximately 2 years

Study Arms (1)

tavo-EP plus IV pembrolizumab

EXPERIMENTAL

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

Biological: tavokinogene telseplasmid; Biological: Pembrolizumab; Device: ImmunoPulse

Interventions

tavokinogene telseplasmid BIOLOGICAL

Intratumoral tavokinogene telseplasmid (tavo, pIL-12) delivered by electroporation every 6 weeks

Also known as: pIL-12, tavo-EP

tavo-EP plus IV pembrolizumab

Pembrolizumab BIOLOGICAL

Intravenous 3 weekly treatments

Also known as: Keytruda

tavo-EP plus IV pembrolizumab

ImmunoPulse DEVICE

Device that electroporates the tavokinogene telseplasmid

Also known as: tavo-EP

tavo-EP plus IV pembrolizumab

Eligibility Criteria

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

You may qualify if:

• In order to be eligible for participation in this study, the subject must meet all of the following:
• All Cohorts:
• 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.
• 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:
• Received treatment of FDA-approved anti-PD1 mAb (dosed per label of the country providing the clinical site) for at least 12 weeks (eg, 4 administrations of q3w 200 mg pembrolizumab or 2 administrations of q6w 400 mg pembrolizumab).
• Progressive disease after anti-PD-1 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. For cases of rapid clinical progression, patients may be allowed to enroll without a confirmatory scan after discussion with the sponsor. (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).
• Documented disease progression within 12 weeks of the last dose of anti- PD-1 mAb. Subjects who were re-treated with anti-PD-1 mAb and subjects who were on maintenance with anti-PD-1 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-PD-1 mAb).
• Note: anti-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.
• Cohort 2:
• Subjects must have received ipilimumab alone or in combination with nivolumab (or another agent) within approximately 12 months and must meet the following criteria:
• Subject received 4 doses of ipilimumab (alone or in combination) or stopped treatment due to treatment-related adverse event, or investigator determined that the risks of further exposure outweigh the benefits.
• Subjects with rapid clinical progression after fewer than 4 doses may be allowed after discussion with the sponsor.
• All Cohorts:
• Resolution/improvement of anti-PD-1 mAb related adverse events (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:
• No history of common toxicity criteria adverse events (CTCAE) Grade 4 irAEs from anti-PD-1 mAb.

You may not qualify if:

• Subject has disease that is suitable for local therapy administered with curative intent.
• 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.
• Subject with a diagnosis of uveal or mucosal melanoma.
• Subject with clinically unstable or uncontrolled secondary malignancy that is progressing, or requires active treatment are excluded. In addition, subjects who have had a secondary malignancy that has resolved within the last 6 months, are also excluded.
• Subject who had an allogenic tissue/solid organ transplant.
• Subjects who have had intervening therapy following confirmed progression on anti-PD-1 therapy or anti-PD-1 combination therapy with the exception of BRAF inhibitors or BRAF/MEK inhibitor combinations.
• Note: anti-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.
• Subjects who have received 4 or more lines of prior therapy, may be allowed to enroll after discussion with the Medical Monitor.
• Subjects with electronic pacemakers or defibrillators.
• Subjects who have a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies). HIV-infected subjects with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
• Subjects who have a known history of Hepatitis B or C infections or known to be positive for Hepatitis B antigen (HBsAg) or Hepatitis B virus (HBV) DNA or active. Active Hepatitis C. Active Hep 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
• 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.
• Subjects who have received a live-virus or live-attenuated vaccination within 30 days of the first dose of treatment. Note: Administration of killed vaccines are allowed. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
• Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Subject has a history of (non infectious) pneumonitis or interstitial lung disease that required steroids or has current pneumonitis or interstitial lung disease.

Sponsors & Collaborators

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

Study Sites (33)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Yuma Regional Medical Center, Yuma Cancer Center

Yuma, Arizona, 85364, United States

Location

University of California, San Diego

La Jolla, California, 92093, United States

Location

UCSF Medical Center

San Francisco, California, 94115, United States

Location

University of Colorado Anschutz Medical Campus University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

University of Miami Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

UF Health Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

Moffit Cancer Center

Tampa, Florida, 33612, United States

Location

Ochsner Cancer Institute

New Orleans, Louisiana, 70121, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan, Michigan Medicine Melanoma Oncology Clinic - Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Dartmouth Hitchcock Clinic

Lebanon, New Hampshire, 03756, United States

Location

Atlantic Health System

Morristown, New Jersey, 07860, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Health Quest Systems, Inc.

Poughkeepsie, New York, 12601, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

St. Luke's University Health Network

Bethlehem, Pennsylvania, 18015, United States

Location

Penn State Health Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Texas Oncology/Baylor

Dallas, Texas, 75246, United States

Location

Houston Methodist Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84107, United States

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Cavalry Central Districts Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

St John of God Hospital

Subiaco, Western Australia, 6008, Australia

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Napoli, 80131, Italy

Location

University of Zurich, Dermatology Clinic

Zurich, Canton of Zurich, Switzerland

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

Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Bridget O'Keeffe, PhD

  OncoSec Medical Incorporated

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Blinded Independent Central Review
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cohort 1A\_Locally advanced/metastatic melanoma: pathological diagnosis of unresectable or metastatic melanoma with progression on pembrolizumab or nivolumab, confirmed according to RECIST v1.1. BRAF V600 mutation-positive melanoma could have received standard of care targeted therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) prior to enrolling on this study; however, progression is not required. Cohort 1B\_Locally advanced/metastatic melanoma: Subjects will be enrolled in order to collect safety data using the GenPulse generator. Eligibility for enrollment will be the same as that for Cohort 1A. Cohort 2\_Locally advanced/metastatic melanoma with prior exposure to ipilimumab alone or in combination with nivolumab (or other drug(s)/agent(s)): Eligible subjects will be those with pathological diagnosis of unresectable or metastatic melanoma who have been exposed to ipilimumab alone or in combination with nivolumab (or other drug/agent)

Study Record Dates

• First Submitted: April 24, 2017
• First Posted: April 28, 2017
• Study Start: October 3, 2017
• Primary Completion: March 31, 2023
• Study Completion: July 31, 2024
• Last Updated: March 27, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

AU (6); CH (1); IT (1); CA (2); US (23)