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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

In order to be eligible for participation in this study, the subject must meet all of the following: All Cohorts: 1. 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.
2. 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: 1. 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). 2. 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). 3. 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: 3. Subjects must have received ipilimumab alone or in combination with nivolumab (or another agent) within approximately 12 months and must meet the following criteria: 1. 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. 2. Subjects with rapid clinical progression after fewer than 4 doses may be allowed after discussion with the sponsor. All Cohorts: 4. 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: 1. No history of common toxicity criteria adverse events (CTCAE) Grade 4 irAEs from anti-PD-1 mAb. 2. No history of CTCAE Grade 3 requiring steroid treatment (>10 mg/day prednisone or equivalent dose) for >12 weeks or CTCAE Grade 2 pneumonitis regardless of steroid treatment. No history of (non-infectious) pneumonitis or interstitial lung disease that required steroids, and no current pneumonitis or interstitial lung disease. 3. Minimum of 4 weeks (washout period) from the last dose of anti-PD-1 mAb. 5. 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 they do not need to have progressed on this treatment. 6. Age ≥ 18 years of age on day of signing informed consent. 7. Has a performance status of 0 or 1 on the ECOG Performance Scale, collected within 7 days of initial treatment. 8. Have measurable disease based on RECIST v1.1, with at least one anatomically distinct lesion. At least one lesion must meet all the following baseline criteria: 1. Accessible for electroporation; 2. Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) Note: Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 9. Demonstrate adequate organ function. All screening laboratories should be performed within 10 days of treatment initiation. 10. Women of childbearing potential must have 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. 11. For women 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 last day of study treatment. Acceptable methods include hormonal contraception (oral contraceptives.
  • - as long as on stable dose, patch, implant, and injection), intrauterine devices, or double barrier methods (eg, vaginal diaphragm/ vaginal sponge plus condom, or condom plus spermicidal jelly), sexual abstinence or a vasectomized partner.
Women may be surgically sterile or at least 1-year post-last menstrual period. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Note: Spermicide alone is not considered sufficient and will not be accepted. 12. Male subjects must be surgically sterile or must agree to use adequate method of contraception when having sex with women of childbearing potential and refrains from sperm donation during the study treatment period and through at least 120 days following the last day of study drug administration.. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 13. Able and willing to provide written informed consent and to follow study instructions.

Exclusion Criteria:

1. Subject has disease that is suitable for local therapy administered with curative intent. 2. 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. 3. Subject with a diagnosis of uveal or mucosal melanoma. 4. 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. 5. Subject who had an allogenic tissue/solid organ transplant. 6. 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. 7. Subjects who have received 4 or more lines of prior therapy, may be allowed to enroll after discussion with the Medical Monitor. 8. Subjects with electronic pacemakers or defibrillators. 9. 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. 10. 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. 11. 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. 12. 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. 13. Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. 14. Subject has a history of (non infectious) pneumonitis or interstitial lung disease that required steroids or has current pneumonitis or interstitial lung disease. 15. 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. 16. Subject has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent, excluding thyroid, hypo adrenal, and diabetes if well controlled. Note: Subjects with ≤Grade 2 neuropathy or ≤Grade 2 alopecia and hypopigmentation are an exception to this criterion and may qualify for the study. Note: Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible if approved by the Sponsor. Note: If subject underwent major surgery or radiation therapy of >30 Gy within 2 weeks of enrollment, they must have recovered adequately from the procedure and/or any complications from the intervention prior to starting study combination therapy. 17. Participation in another clinical study of an investigational anti-cancer agent or has used an investigational device within 30 days of screening. Note: Subjects participating in an observational or supportive care study are an exception to this criterion and may qualify for the study with Sponsor approval. Note: Subjects who have entered the follow up phase of an investigational study may participate as long as it has been 30 days after the last dose of the previous investigational agent. 18. Subject has known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study. 19. Subjects who are pregnant or breast-feeding 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03132675
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

OncoSec Medical Incorporated
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Bridget O'Keeffe, PhD
Principal Investigator Affiliation OncoSec Medical Incorporated
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Australia, Canada, Italy, Switzerland, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Stage III/IV Melanoma
Additional Details

The study will be comprised of a screening period, a treatment period (up to 2 years), a long term follow-up period, and a survival follow-up period. Eligible subjects will be treated with 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 18 TAVO-EP cycles and 35 pembrolizumab cycles (from baseline) of continued treatment (approximately 2 years) or until disease progression. As many accessible lesions may be treated, as deemed feasible by the treating physician, as long as the size of each lesion is greater than 0.3 cm × 0.3 cm. Long-term Follow-up: All subjects will be followed after End of Treatment (EOT) visit for SAEs (through 90 days from last dose of study drug). Subjects who discontinue treatment will enter the long-term follow-up period unless they have started a new anti-cancer therapy (or other local anticancer immunotherapy) or have withdrawn consent for non-survival assessments. They will have scans, photographs, and investigator-assessed disease evaluation per RECIST v1.1 collected every 3 months until disease progression, or the subject receives a new systemic anti-cancer treatment (or other local anticancer immunotherapy). Survival Follow-up: Once a subject receives a new systemic anti-cancer treatment (or other local anticancer immunotherapy), they will move into survival follow-up. All subjects will be followed for survival and disease status, every 3 months up to a total duration of 5 years, withdrawal of consent, or until Sponsor terminates the study.

Arms & Interventions

Arms

Experimental: tavo-EP plus IV pembrolizumab

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

Interventions

Biological: - tavokinogene telseplasmid

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

Biological: - Pembrolizumab

Intravenous 3 weekly treatments

Device: - ImmunoPulse

Device that electroporates the tavokinogene telseplasmid

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

The University of Arizona Cancer Center, Tucson, Arizona

Status

Recruiting

Address

The University of Arizona Cancer Center

Tucson, Arizona, 85724

Yuma, Arizona

Status

Recruiting

Address

Yuma Regional Medical Center, Yuma Cancer Center

Yuma, Arizona, 85364

University of California, San Diego, La Jolla, California

Status

Recruiting

Address

University of California, San Diego

La Jolla, California, 92093

UCSF Medical Center, San Francisco, California

Status

Recruiting

Address

UCSF Medical Center

San Francisco, California, 94115

Aurora, Colorado

Status

Recruiting

Address

University of Colorado Anschutz Medical Campus University of Colorado Cancer Center

Aurora, Colorado, 80045

Miami, Florida

Status

Recruiting

Address

University of Miami Sylvester Cancer Center

Miami, Florida, 33136

Orlando, Florida

Status

Recruiting

Address

UF Health Cancer Center at Orlando Health

Orlando, Florida, 32806

Moffit Cancer Center, Tampa, Florida

Status

Completed

Address

Moffit Cancer Center

Tampa, Florida, 33612

Chicago, Illinois

Status

Withdrawn

Address

Northwestern University, Northwestern Medicine Feinger School of Medicine

Chicago, Illinois, 60611

Ochsner Cancer Institute, New Orleans, Louisiana

Status

Recruiting

Address

Ochsner Cancer Institute

New Orleans, Louisiana, 70121

Dana-Farber Cancer Institute, Boston, Massachusetts

Status

Completed

Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Ann Arbor, Michigan

Status

Completed

Address

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

Ann Arbor, Michigan, 48109

Health Partners Cancer Care Center, Saint Paul, Minnesota

Status

Withdrawn

Address

Health Partners Cancer Care Center

Saint Paul, Minnesota, 55101

Dartmouth Hitchcock Clinic, Lebanon, New Hampshire

Status

Recruiting

Address

Dartmouth Hitchcock Clinic

Lebanon, New Hampshire, 03756

Atlantic Health System, Morristown, New Jersey

Status

Completed

Address

Atlantic Health System

Morristown, New Jersey, 07860

Roswell Park Cancer Institute, Buffalo, New York

Status

Completed

Address

Roswell Park Cancer Institute

Buffalo, New York, 14263

Health Quest Systems, Inc., Poughkeepsie, New York

Status

Completed

Address

Health Quest Systems, Inc.

Poughkeepsie, New York, 12601

Duke University, Durham, North Carolina

Status

Completed

Address

Duke University

Durham, North Carolina, 27710

Gabrail Cancer Center, Canton, Ohio

Status

Completed

Address

Gabrail Cancer Center

Canton, Ohio, 44718

University of Toledo, Toledo, Ohio

Status

Withdrawn

Address

University of Toledo

Toledo, Ohio, 43614

St. Luke's University Health Network, Bethlehem, Pennsylvania

Status

Completed

Address

St. Luke's University Health Network

Bethlehem, Pennsylvania, 18015

Penn State Health Hershey Medical Center, Hershey, Pennsylvania

Status

Completed

Address

Penn State Health Hershey Medical Center

Hershey, Pennsylvania, 17033

Fox Chase Cancer Center, Philadelphia, Pennsylvania

Status

Recruiting

Address

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

Texas Oncology/Baylor, Dallas, Texas

Status

Recruiting

Address

Texas Oncology/Baylor

Dallas, Texas, 75246

Houston Methodist Cancer Center, Houston, Texas

Status

Completed

Address

Houston Methodist Cancer Center

Houston, Texas, 77030

Huntsman Cancer Institute, Salt Lake City, Utah

Status

Completed

Address

Huntsman Cancer Institute

Salt Lake City, Utah, 84107

International Sites

Westmead Hospital, Westmead, New South Wales, Australia

Status

Completed

Address

Westmead Hospital

Westmead, New South Wales, 2145

Princess Alexandra Hospital, Woolloongabba, Queensland, Australia

Status

Completed

Address

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102

Cavalry Central Districts Hospital, Elizabeth Vale, South Australia, Australia

Status

Completed

Address

Cavalry Central Districts Hospital

Elizabeth Vale, South Australia, 5112

Box Hill Hospital, Box Hill, Victoria, Australia

Status

Completed

Address

Box Hill Hospital

Box Hill, Victoria, 3128

The Alfred Hospital, Melbourne, Victoria, Australia

Status

Completed

Address

The Alfred Hospital

Melbourne, Victoria, 3004

Affinity Clinical Research, Nedlands, Western Australia, Australia

Status

Withdrawn

Address

Affinity Clinical Research

Nedlands, Western Australia, 6009

St John of God Hospital, Subiaco, Western Australia, Australia

Status

Completed

Address

St John of God Hospital

Subiaco, Western Australia, 6008

The Moncton Hospital, Moncton, New Brunswick, Canada

Status

Withdrawn

Address

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8

Princess Margaret Cancer Centre, Toronto, Ontario, Canada

Status

Completed

Address

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9

McGill University Health Centre, Montréal, Quebec, Canada

Status

Completed

Address

McGill University Health Centre

Montréal, Quebec, H4A 3J1

Napoli, Italy

Status

Completed

Address

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Napoli, , 80131

University of Zurich, Dermatology Clinic, Zürich, Canton Of Zurich, Switzerland

Status

Completed

Address

University of Zurich, Dermatology Clinic

Zürich, Canton Of Zurich,

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