Condition or disease | Intervention/treatment | Phase |
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Stage III/IV Melanoma | Biological: tavokinogene telseplasmid Biological: Pembrolizumab Device: ImmunoPulse | Phase 2 |
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 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 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 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) Treatment visit for SAEs (through 90 days from last dose of study drug). Subjects who discontinue treatment due to disease progression will directly enter the survival follow-up period following the End of Study Treatment visit. Subjects who discontinue treatment for any reason other than disease progression or withdrawal of consent enter the long-term follow-up period. They will have scans, photographs, and investigator-assessed disease evaluation per RECIST v1.1 collected every 3 months until disease progression, subject receives a new anti-cancer treatment (with the exception of maintenance pembrolizumab).
Information on all subjects' first new anti-cancer therapy will also be collected.
Survival Follow-up: Once a subject receives a new anti-cancer treatment or progresses during long-term follow-up, they will move into survival follow-up. All subjects will be followed for survival and disease status-, every 3 months until treatment period, long-term follow-up period, and survival follow-up period reaches a total duration of 5 years, withdrawal of consent, or until Sponsor terminates the study.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 152 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | Phase 2, non-comparative, open-label, single-arm, multicenter study of intatrumoral tavo-EP plus IV pembrolizumab. Cohort 1 Locally advanced or metastatic melanoma: Approximatey 100 evaluable subjects will be enrolled into this cohort. The sample site may increase by up to an additional 25 subjects in order to collect clinical experience with the GenPulse OMS electroporation device. Cohort 2 Locally advanced or metastatic melanoma with prior exposure to ipilimumab in combination with nivolumab: Approximately 27 subjects will be enrolled into the cohort. Eligible subjects will be those with pathological diagnosis of unresectable or metastatic melanoma who are progressing or have progressed on ipilimumab combined with nivolumab. |
Masking: | None (Open Label) |
Masking Description: | Blinded Independent Central Review |
Primary Purpose: | Treatment |
Official Title: | A Multicenter Phase 2, Open Label Study of Intratumoral Tavokinogene Telseplasmid (Tavo, pIL-12) 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) |
Actual Study Start Date : | October 3, 2017 |
Estimated Primary Completion Date : | December 31, 2022 |
Estimated Study Completion Date : | July 31, 2023 |
Arm | Intervention/treatment |
---|---|
Experimental: tavo-EP plus IV pembrolizumab
Intratumoral Tavokinogene Telseplasmid (tavo, pIL 12) plus Electroporation (ImmunoPulse) in Combination with Intravenous Pembrolizumab
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Biological: tavokinogene telseplasmid
Intratumoral tavokinogene telseplasmid (tavo, pIL-12) delivered by electroporation every 6 weeks
Other Names:
Biological: Pembrolizumab Intravenous 3 weekly treatments
Other Name: Keytruda
Device: ImmunoPulse Device that electroporates the tavokinogene telseplasmid
Other Name: tavo-EP
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
In order to be eligible for participation in this study, the subject must meet all of the following:
All Cohorts:
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:
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 in combination with nivolumab and must meet the following criteria:
All Cohorts:
Resolution/improvement of anti-PD-1 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-PD-1 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-PD-1 mAb
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:
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
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.
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
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.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Exclusion Criteria:
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.
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.
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.
Contact: Chris Baker | 609-802-6632 | cbaker@oncosec.com | |
Contact: Jendy Sell | 610.703.3418 | jsell@oncosec.com |
Study Director: | Jendy Sell | OncoSec Medical Incorporated |
Tracking Information | |||||||||
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First Submitted Date ICMJE | April 24, 2017 | ||||||||
First Posted Date ICMJE | April 28, 2017 | ||||||||
Last Update Posted Date | April 29, 2021 | ||||||||
Actual Study Start Date ICMJE | October 3, 2017 | ||||||||
Estimated Primary Completion Date | December 31, 2022 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Overall Response Rate (ORR) [ Time Frame: approximately 2 years ] ORR by blinded independent central review (BICR) based on RECIST v1.1
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Original Primary Outcome Measures ICMJE |
Best Overall Response Rate (BORR) [ Time Frame: over 24 weeks ] BORR by independent central review based on RECIST v1.1
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Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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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 Tavokinogene Telseplasmid (Tavo, pIL-12) 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), a long term follow-up period, and a survival follow-up period. 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 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 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) Treatment visit for SAEs (through 90 days from last dose of study drug). Subjects who discontinue treatment due to disease progression will directly enter the survival follow-up period following the End of Study Treatment visit. Subjects who discontinue treatment for any reason other than disease progression or withdrawal of consent enter the long-term follow-up period. They will have scans, photographs, and investigator-assessed disease evaluation per RECIST v1.1 collected every 3 months until disease progression, subject receives a new anti-cancer treatment (with the exception of maintenance pembrolizumab). Information on all subjects' first new anti-cancer therapy will also be collected. Survival Follow-up: Once a subject receives a new anti-cancer treatment or progresses during long-term follow-up, they will move into survival follow-up. All subjects will be followed for survival and disease status-, every 3 months until treatment period, long-term follow-up period, and survival follow-up period reaches a total duration of 5 years, withdrawal of consent, or until Sponsor terminates the study. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Intervention Model Description: Phase 2, non-comparative, open-label, single-arm, multicenter study of intatrumoral tavo-EP plus IV pembrolizumab. Cohort 1 Locally advanced or metastatic melanoma: Approximatey 100 evaluable subjects will be enrolled into this cohort. The sample site may increase by up to an additional 25 subjects in order to collect clinical experience with the GenPulse OMS electroporation device. Cohort 2 Locally advanced or metastatic melanoma with prior exposure to ipilimumab in combination with nivolumab: Approximately 27 subjects will be enrolled into the cohort. Eligible subjects will be those with pathological diagnosis of unresectable or metastatic melanoma who are progressing or have progressed on ipilimumab combined with nivolumab. Masking Description: Blinded Independent Central Review Primary Purpose: Treatment
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Condition ICMJE | Stage III/IV Melanoma | ||||||||
Intervention ICMJE |
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Study Arms ICMJE | Experimental: tavo-EP plus IV pembrolizumab
Intratumoral Tavokinogene Telseplasmid (tavo, pIL 12) plus Electroporation (ImmunoPulse) in Combination with Intravenous Pembrolizumab
Interventions:
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
152 | ||||||||
Original Estimated Enrollment ICMJE |
48 | ||||||||
Estimated Study Completion Date ICMJE | July 31, 2023 | ||||||||
Estimated Primary Completion Date | December 31, 2022 (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: All Cohorts:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Australia, Canada, Switzerland, United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03132675 | ||||||||
Other Study ID Numbers ICMJE | OMS-I103 (KEYNOTE 695) Keynote-695 ( Other Identifier: Merck & Co ) MK3475-695 ( Other Identifier: Merck & Co ) |
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Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | OncoSec Medical Incorporated | ||||||||
Study Sponsor ICMJE | OncoSec Medical Incorporated | ||||||||
Collaborators ICMJE | Merck Sharp & Dohme Corp. | ||||||||
Investigators ICMJE |
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PRS Account | OncoSec Medical Incorporated | ||||||||
Verification Date | April 2021 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |