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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03132675




Registration number
NCT03132675
Ethics application status
Date submitted
24/04/2017
Date registered
28/04/2017

Titles & IDs
Public title
Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Either Pembrolizumab or Nivolumab Treatment
Scientific title
A Multicenter Phase 2, Open Label Study of Intratumoral Tavokinogene Telseplasmid (Tavo, pIL-12) + Electroporation With Pembrolizumab in Patients With Stage 3/4 Melanoma Who Are Progressing on Either Pembrolizumab or Nivolumab Treatment
Secondary ID [1] 0 0
Keynote-695
Secondary ID [2] 0 0
OMS-I103 (KEYNOTE 695)
Universal Trial Number (UTN)
Trial acronym
Keynote-695
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stage III/IV Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - tavokinogene telseplasmid
Treatment: Other - Pembrolizumab
Treatment: Devices - ImmunoPulse

Experimental: tavo-EP plus IV pembrolizumab - Intratumoral Tavokinogene Telseplasmid (tavo, pIL 12) plus Electroporation (ImmunoPulse) in Combination with Intravenous Pembrolizumab


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

Treatment: Other: Pembrolizumab
Intravenous 3 weekly treatments

Treatment: Devices: ImmunoPulse
Device that electroporates the tavokinogene telseplasmid
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
approximately 2 years
Secondary outcome [1] 0 0
Objective Response rate (ORR)
Timepoint [1] 0 0
approximately 2 years
Secondary outcome [2] 0 0
Duration of Response (DOR)
Timepoint [2] 0 0
approximately 2 years
Secondary outcome [3] 0 0
Progression free survival (PFS)
Timepoint [3] 0 0
approximately 2 years
Secondary outcome [4] 0 0
Immune Progression Free Survival (iPFS)
Timepoint [4] 0 0
approximately 2 years
Secondary outcome [5] 0 0
Immune Overall Response Rate (iORR)
Timepoint [5] 0 0
approximately 2 years
Secondary outcome [6] 0 0
Overall survival (OS)
Timepoint [6] 0 0
approximately 2 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2024
Actual
Sample size
Target
143
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Cavalry Central Districts Hospital - Elizabeth Vale
Recruitment hospital [4] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [5] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [6] 0 0
St John of God Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
New Hampshire
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Italy
State/province [18] 0 0
Napoli
Country [19] 0 0
Switzerland
State/province [19] 0 0
Canton Of Zurich

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
OncoSec Medical Incorporated
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bridget O'Keeffe, PhD
Address 0 0
OncoSec Medical Incorporated
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
There is a DSMB charter that makes anonymised data available.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03132675