Stage III/IV Melanoma MedDRA version: 21.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: tavokinogene telseplasmid
Product Code: [pUMVC3-hIL12, pIL-12, IL-12, hIL-12]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: TAVOKINOGENE TELSEPLASMID
CAS Number: 19718
Sponsors
OncoSec Medical Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Pathologically documented unresectable melanoma, AJCC ver 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 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: -Received treatment of FDA-approved anti PD1 mAb (dosed per label of the country providing the clinical site) for at least 12 weeks -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 enrolled without confirmatory scan. (Determination made by Investigator; 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) -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: -No history of CTCAE Grade 4 irAEs from anti PD1 mAb -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 -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. At least one lesion must meet all the following baseline criteria: -Accessible for electroporation -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 followi
Exclusion criteria
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 4weeks by repeat imaging (the repeat imaging should be performed during study screening),clinically stable and without requirement of steroid treatment for at least 14days prior to first dose of study drug. 3.Subject with a diagnosis of uveal melanoma 4. Subjects 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 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 HBsAg or HBV DNA or active Hepatitis C.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 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 30days 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, breast-feeding or expecting to conceive within the study through 120 days after the last dose of study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Overall Response Rate by blinded independent central review (BICR) based on RECIST v1.1.;Secondary Objective: • Assess safety and tolerability of the combined treatment in subjects with unresectable or metastatic melanoma who previously have progressed on prior approved anti-PD-1 antibodies • Assess duration of response (DOR), ORR, immune OR (iORR), PFS, immune PFS (iPFS), and OS of combination therapy • Assess long-term safety and tolerability of the combination therapy;Primary end point(s): Overall Response Rate by blinded independent central review (BICR) based on RECIST v1.1;Timepoint(s) of evaluation of this end point: Approximately 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Objective Response rate by investigator assessment based on RECIST v1.1 • Duration of Response by Investigator assessment and BICR based on RECIST v1.1 • Progression free survival by investigator assessment and BICR based on RECIST v1.1 • Immune Progression Free Survival by Investigator assessment and BICR based on iRECIST • Immune Overall Response Rate by Investigator assessment and BICR based on iRECIST • Overall survival;Timepoint(s) of evaluation of this end point: Approximately 2 years | — |
Countries
Australia, Canada, Germany, Italy, Poland, United States
Contacts
Public ContactStudy Director
OncoSec Medical Incorporated
Outcome results
None listed