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Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Pembrolizumab or Nivolumab Treatment (Keynote695)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03132675
Recruitment Status : Recruiting
First Posted : April 28, 2017
Last Update Posted : February 24, 2020
Sponsor:
Information provided by (Responsible Party):
OncoSec Medical Incorporated

Tracking Information
First Submitted Date  ICMJE April 24, 2017
First Posted Date  ICMJE April 28, 2017
Last Update Posted Date February 24, 2020
Actual Study Start Date  ICMJE October 3, 2017
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2019)
Overall Response Rate (ORR) [ Time Frame: approximately 2 years ]
ORR by blinded independent central review (BICR) based on RECIST v1.1
Original Primary Outcome Measures  ICMJE
 (submitted: April 26, 2017)
Best Overall Response Rate (BORR) [ Time Frame: over 24 weeks ]
BORR by independent central review based on RECIST v1.1
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2019)
  • Objective Response rate (ORR) [ Time Frame: approximately 2 years ]
    ORR by investigator assessment based on RECIST v1.1
  • Duration of Response (DOR) [ Time Frame: approximately 2 years ]
    DOR by Investigator assessment and BICR based on RECIST v1.1
  • Progression free survival (PFS) [ Time Frame: approximately 2 years ]
    PFS by investigator assessment and BICR based on RECIST v1.1
  • Immune Progression Free Survival (iPFS) [ Time Frame: approximately 2 years ]
    iPFS by Investigator assessment and BICR based on iRECIST
  • Immune Overall Response Rate (iORR) [ Time Frame: approximately 2 years ]
    iORR by Investigator assessment and BICR based on iRECIST
  • Overall survival (OS) [ Time Frame: approximately 2 years ]
    Overall survival
Original Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2017)
  • Objective Response rate [ Time Frame: approximately 2 years ]
    ORR by investigator assessment and by independent central review based on RECIST v1.1
  • Duration [ Time Frame: approximately 2 years ]
    Duration by investigator assessment and by independent central review based on RECIST v1.1
  • Progression free survival (PFS) [ Time Frame: approximately 2 years ]
    PFS by investigator assessment and by independent central review based on RECIST v1.1
  • Overall survival [ Time Frame: approximately 2 years ]
    Overall survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Pembrolizumab or Nivolumab Treatment
Official Title  ICMJE A Multicenter Phase 2, Open Label Study of Intratumoral Tavo Plus Electroporation in Combination With Intravenous Pembrolizumab in Patients With Stage III/IV Melanoma Who Are Progressing on Either Pembrolizumab or Nivolumab Treatment (Keynote 695)
Brief Summary Keynote 695 will be a 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 pembrolizumab or nivolumab.
Detailed Description

The study will be comprised of a screening period, a treatment period (up to 2 years) and a long term follow-up.

Eligible patients will be treated with intratumoral tavo-EP to the accessible lesions on Days 1, 5 and 8 every 6 weeks and with IV pembrolizumab (200mg) on Day 1 of each 3-week cycle for 17 tavo-EP cycles and 33 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 assuming the size of each lesion is greater than 0.3 cm x 0.3 cm.

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Phase 2, non-comparative, open-label, single-arm, multicenter study
Masking: None (Open Label)
Masking Description:
Blinded Independent Central Review
Primary Purpose: Treatment
Condition  ICMJE Stage III/IV Melanoma
Intervention  ICMJE
  • Biological: tavokinogene telseplasmid
    Intratumoral tavokinogene telseplasmid (tavo, pIL-12) 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 electroporates the tavokinogene telseplasmid
    Other Name: tavo-EP
Study Arms  ICMJE Experimental: tavo-EP plus IV pembrolizumab
Intratumoral Tavokinogene Telseplasmid (tavo, pIL 12) plus Electroporation (ImmunoPulse) in Combination with Intravenous Pembrolizumab
Interventions:
  • Biological: tavokinogene telseplasmid
  • Biological: Pembrolizumab
  • Device: ImmunoPulse
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 21, 2019)
100
Original Estimated Enrollment  ICMJE
 (submitted: April 26, 2017)
48
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

In order to be eligible for participation in this study, the subject must meet all of the following:

  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.
    2. Progressive disease after anti PD1 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. (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 PD1 mAb. Subjects who were re treated with anti PD1 mAb and subjects who were on maintenance with anti PD1 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 PD1 mAb).
  3. Resolution/improvement of anti PD1 mAb related AEs (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 PD1 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.
    3. Minimum of 4 weeks (washout period) from the last dose of anti PD1 mAb
  4. Prior treatment with an approved BRAF inhibitor if BRAF V600 mutation positive.
  5. Age ≥ 18 years of age on day of signing informed consent.
  6. Has a performance status of 0 or 1 on the ECOG Performance Scale, collected within 7 days of initial treatment.
  7. Have measurable disease based on RECIST v1.1, with at least one anatomically distinct lesion. Lesion or lesions 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
  8. Demonstrate adequate organ function. All screening laboratories should be performed within 10 days of treatment initiation.
  9. Women of childbearing potential must have negative serum or urine pregnancy test within 72 hours 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.
  10. 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). Acceptable methods include hormonal contraception (oral contraceptives - as long as on stable dose, patch, implant, and injection), intrauterine devices, or double barrier methods (e.g. 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.
  11. Male subjects must be surgically sterile or must agree to use adequate method of contraception during the study and at least 120 days following the last day of study drug administration.
  12. 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. Subject with a diagnosis of uveal or mucosal melanoma.
  3. Subject has a known additional malignancy that is progressing or requires active treatment within the past 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  4. 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.
  5. Greater than 3 visceral sites of metastases (this does not include nodal metastases associated with visceral organs)
  6. Subjects with stage IVc melanoma with liver or bowel metastases.
  7. Subject who had an allogenic tissue/solid organ transplant.
  8. Subjects with electronic pacemakers or defibrillators.
  9. Subjects who have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). HIV-infected subjects with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
  10. Subjects who have history of Hepatitis B or C infections or 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 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 vaccination within 30 days of the first dose of treatment. Seasonal flu 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. 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 4 weeks prior to study Cycle 1, Day 1 (baseline).
  15. Subject has a history of (non infectious) pneumonitis that required steroids or current pneumonitis.
  16. Subject has a history of interstitial lung disease.
  17. Subject has an active infection requiring systemic therapy.
  18. 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.
  19. Subject has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  20. Participation in another clinical study of an investigational anti-cancer agent or has used an investigational device within 30 days of screening.
  21. Subjects who have had intervening therapy following confirmed progression on anti PD 1 therapy or anti-PD-1 combination therapy with the exception of approved BRAF/MEK inhibitor combinations. 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.
  22. Subject has known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
  23. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Chris Baker 609-802-6632 cbaker@oncosec.com
Contact: Kellie Malloy 609-977-4193 kmalloy@oncosec.com
Listed Location Countries  ICMJE Australia,   Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03132675
Other Study ID Numbers  ICMJE OMS-I103 (KEYNOTE 695)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: There is a DSMB charter that make anonymised data available
Responsible Party OncoSec Medical Incorporated
Study Sponsor  ICMJE OncoSec Medical Incorporated
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kellie Malloy OncoSec Medical Incorporated
PRS Account OncoSec Medical Incorporated
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP