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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03132675
Ethics application status
Date submitted
24/04/2017
Date registered
28/04/2017
Date last updated
24/08/2020

Titles & IDs
Public title
Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Pembrolizumab or Nivolumab Treatment
Scientific title
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)
Secondary ID [1] 0 0
OMS-I103 (KEYNOTE 695)
Universal Trial Number (UTN)
Trial acronym
Keynote695
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
Other interventions - tavokinogene telseplasmid
Other interventions - Pembrolizumab
Treatment: Devices - ImmunoPulse

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


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

Other interventions: Pembrolizumab
Intravenous 3 weekly treatments

Treatment: Devices: ImmunoPulse
Device that electroporates the tavokinogene telseplasmid

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) - ORR by blinded independent central review (BICR) based on RECIST v1.1
Timepoint [1] 0 0
approximately 2 years
Secondary outcome [1] 0 0
Objective Response rate (ORR) - ORR by investigator assessment based on RECIST v1.1
Timepoint [1] 0 0
approximately 2 years
Secondary outcome [2] 0 0
Duration of Response (DOR) - DOR by Investigator assessment and BICR based on RECIST v1.1
Timepoint [2] 0 0
approximately 2 years
Secondary outcome [3] 0 0
Progression free survival (PFS) - PFS by investigator assessment and BICR based on RECIST v1.1
Timepoint [3] 0 0
approximately 2 years
Secondary outcome [4] 0 0
Immune Progression Free Survival (iPFS) - iPFS by Investigator assessment and BICR based on iRECIST
Timepoint [4] 0 0
approximately 2 years
Secondary outcome [5] 0 0
Immune Overall Response Rate (iORR) - iORR by Investigator assessment and BICR based on iRECIST
Timepoint [5] 0 0
approximately 2 years
Secondary outcome [6] 0 0
Overall survival (OS) - Overall survival
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:

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. 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 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:

d. No history of common toxicity criteria adverse events (CTCAE) Grade 4 irAEs from
anti PD1 mAb.

e. 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.

f. Minimum of 4 weeks (washout period) from the last dose of anti PD1 mAb

4. 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.

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:

g. Accessible for electroporation; h. 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.
Minimum age
18 Years
Maximum age
No limit
Gender
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 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 with electronic pacemakers or defibrillators.

7. 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.

8. 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 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

9. 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.

10. 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.

11. Subject has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its
excipients.

12. Subject has a history of (non infectious) interstitial pneumonitis that required
steroids or current pneumonitis or any active infection requiring systemic therapy.

13. 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.

14. 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.

15. Participation in another clinical study of an investigational anti-cancer agent or has
used an investigational device within 30 days of screening.

16. 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. 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.

17. Subject has known psychiatric or substance abuse disorder that would interfere with
the subject's ability to cooperate with the requirements of the study.

18. 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
N/A
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
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
Affinity Clinical Research - Nedlands
Recruitment hospital [7] 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
6009 - Nedlands
Recruitment postcode(s) [7] 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
Illinois
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
Minnesota
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
New Brunswick
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
OncoSec Medical Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03132675
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kellie Malloy
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
Chris Baker
Address 0 0
Country 0 0
Phone 0 0
609-802-6632
Fax 0 0
Email 0 0
cbaker@oncosec.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03132675