- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03003676
A Pilot Study of Sequential ONCOS-102, an Engineered Oncolytic Adenovirus Expressing GMCSF, and Pembrolizumab in Patients With Advanced or Unresectable Melanoma Progressing After Programmed Cell Death Protein 1 (PD1) Blockade
A Pilot Study of Sequential ONCOS-102, an Engineered Oncolytic Adenovirus Expressing GMCSF, and Pembrolizumab in Patients With Advanced or Unresectable Melanoma Progressing After PD1 Blockade
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Oslo, Norway
- Oslo University Hospital - The Norwegian Radium Hospital
-
-
-
-
Maryland
-
Baltimore, Maryland, United States
- University of Maryland Comprehensive Cancer Center
-
-
New York
-
New York, New York, United States
- Memorial Sloan Kettering Cancer Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States
- Fox Chase Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adults 18 years of age or older.
- For US sites: Histopathologically confirmed melanoma with an injectable cutaneous or lymph node metastasis that has progressed in the opinion of the treating investigator despite administering a Food and Drug Administration (FDA) approved anti-PD1 agent, with or without ipilimumab.
- For European sites: Histopathologically confirmed melanoma with an injectable cutaneous or lymph node metastasis that has progressed in the opinion of the treating investigator despite administering a regulatory approved anti-PD1 agent, with or without ipilimumab.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
- Measurable disease according to RECIST 1.1.
- Acceptable coagulation status: international normalised ratio (INR) of blood clotting, prothrombin time and activated partial thromboplastin time within ≤1.5 x upper limit of normal (ULN).
- Completion of local therapy, such as radiation, surgical resection, injectable immunebased therapy, or topical pro-inflammatory agent, 21 days prior to first dose of protocol therapy.
- Adverse events from previous cancer therapies (excluding alopecia) must have recovered to grade 1 (CTCAE, most recent version). Stable grade 2 AEs such as endocrine conditions are allowed, and other chronic stable AEs may be considered on a case by case basis by the Principal Investigator.
- Clinical stability of brain metastases for at least 4 weeks prior to first day of study therapy.
Acceptable liver and renal functions defined as:
- Total bilirubin ≤1.5 x ULN (does not include patients with Gilbert's Disease)
- Aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT) ≤3.0 x ULN
- Serum creatinine ≤1.5 x ULN
Acceptable haematological function defined as (Patients can be transfused to meet the haemoglobin entry criteria):
- Haemoglobin ≥9 g/dL
- Neutrophils ≥1.5 x 10^9/L
- Platelet count ≥75 x 10^9/L
- Able to provide valid written informed consent.
- All women of childbearing potential must have a negative urine or serum pregnancy test at screening.
- For US sites: All patients must agree to use barrier contraception (i.e. condom) during study treatment and for 2 months after the last virus treatment and 4 months after the last dose of chemotherapy and pembrolizumab.
- For European sites: All patients must agree to use highly effective contraception for at least 6 months (according to the latest country specific SmPC) after administration of CPO, up to 4 months after last dose of pembrolizumab, and up to 2 months after last dose of ONCOS-102, whichever comes last.
- For European sites: All women of child-bearing potential must agree to perform pregnancy testing throughout the study starting at baseline, every 3 weeks from day 22 until last dose of study medication (ONCOS-102 and pembrolizumab) and then every month for at least 6 months.
Exclusion Criteria:
- A concomitant medical condition requiring receipt of a therapeutic anticoagulant that in the opinion of the treating physician cannot safely allow for therapeutic injection of ONCOS-102 and tumor biopsies. Local clinical practice can be followed with regard to holding a therapeutic anticoagulant during invasive procedures such as biopsies.
- A concomitant medical condition that in the opinion of the treating physician would pose unreasonable additional risk to therapeutic injection of ONCOS-102.
- For US sites: Receipt of Investigational agents within 28 days prior to first dose of protocol therapy.
- For European sites: Current participation or participation in a study of an investigational agent within 28 days prior to first dose of protocol therapy. Note: participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Any symptomatic autoimmune disease (such as lupus, scleroderma, Crohn's disease, ulcerative colitis) that requires administration of >10mg of prednisone equivalent. Lower dose steroids for conditions such as hypophysitis are allowed.
Any prior severe adverse event attributed to prior anti-PD1 therapy that, in the Principal investigator's opinion, would contraindicate pembrolizumab administration such as:
- Grade 2 or higher pneumonitis
- Grade 4 AST or ALT elevation
- Grade 3 or higher colitis attributable to PD1 blockade; note that colitis attributable to ipilimumab is not excluded
- Note: in the absence of clinical symptoms of pancreatitis, elevations of amylase or lipase are not contraindications to therapy on this trial
- Known active infection with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV. Cleared HBV/HCV infection is not an exclusion, nor is HIV infection with cluster of differentiations 4 (CD4) counts >500 and an undetectable viral load.
- Active bacterial, viral, or fungal infections, requiring systemic therapy apart from anti-viral maintenance therapy for HIV.
- History of organ transplant.
- Patients requiring chronic systemic immunosuppressants, including steroids (prednisone daily equivalent of >10 mg).
- Brain metastases that are clinically unstable (e.g. showing unequivocal growth on imaging, requiring radiation therapy, or steroids >10mg of prednisone equivalent) within 4 weeks of first dose of study drug.
- Known severe congenital or acquired cellular or humoral immunodeficiency such as common variable immunodeficiency.
- For US sites: Women who are pregnant or breast-feeding currently or are planning to conceive during or up to 4 months after end of protocol therapy.
- For European sites: Women who are currently pregnant or breast-feeding or are planning to conceive during or up to 6 months after end of protocol therapy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Experimental: ONCOS-102+cyclophosphamide+pembrolizumab
Part I: Patients will receive 3 doses of intratumoral (i.t.) injection of ONCOS-102 (days 1, 4, and 8) at 3x10^11 viral particles (VP), preceded by intravenous (i.v.) cyclophosphamide priming 1-3 days prior to day 1. They will then receive pembrolizumab i.v., 2mg/kg or 200mg flat dose, on day 22 (Week 3) and every 3 weeks thereafter until the end of treatment visit on day 169 (Week 24). Part II: Patients will receive 4 doses of intratumoral (i.t.) injection of ONCOS-102 (days 1, 4, 8 and 15) at 3x10^11 viral particles (VP), preceded by intravenous (i.v.) cyclophosphamide priming 1-3 days prior to day 1. ONCOS-102 will be given in combination with Pembrolizumab starting on Day 22/Week 3 and every three weeks thereafter until Day 169/Week 24 or until unacceptable toxicity or clinically relevant disease progression, whichever occurs first. Pembrolizumab will be given according to institutional practice (2mg/kg or 200mg flat dose). |
Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF)
Pre-treatment
PD1 blockade
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of Treatment-emergent Adverse Events Including Treatment-emergent Serious Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame: 6 months
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Objective Response Rates by RECIST 1.1 and irRECIST.
Time Frame: 6 months
|
6 months
|
Changes in Immune Cell Subsets in Tumor Tissue Before and After ONCOS-102 and Pembrolizumab.
Time Frame: 6 months
|
6 months
|
Changes in Immune Cell Subsets in Peripheral Blood Before and After ONCOS-102 and Pembrolizumab.
Time Frame: 6 months
|
6 months
|
Correlation of Tumour Infiltrating Lymphocytes (TILs) and Overall Response Rate (ORR).
Time Frame: 6 months
|
6 months
|
Progression Free Survival (PFS) Assessed by RECIST 1.1 and irRECIST.
Time Frame: 6 months
|
6 months
|
Clinical Benefit Rate, Defined as Any Confirmed Objective Response by RECIST 1.1 or Stable Disease.
Time Frame: 6 months
|
6 months
|
Clinical Benefit Rate, Defined as Any Objective Response by irRECIST Criteria or Immune-related Stable Disease.
Time Frame: 6 months
|
6 months
|
Change in Size in Individual Lesions.
Time Frame: 6 months
|
6 months
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Somatic Mutational Rate and Neoepitope Burden in Tumors and Explore Relationship to Response.
Time Frame: 6 months
|
6 months
|
Changes in T Cell Receptor Clonality in Infiltrating and Circulating T Cells.
Time Frame: 6 months
|
6 months
|
Gene Expression Changes in the Tumor Microenvironment and Peripheral Blood.
Time Frame: 6 months
|
6 months
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Immunological
- Cyclophosphamide
- Pembrolizumab
Other Study ID Numbers
- ONCOS C824
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced or Unresectable Melanoma Progressing After PD1 Blockade
-
Bristol-Myers SquibbNo longer availableStage III (Unresectable) or Stage IV Advanced MelanomaUnited States, Canada, Argentina, Colombia, Peru, Brazil
-
Karyopharm Therapeutics IncActive, not recruitingLocally Advanced Unresectable or Metastatic MelanomaUnited States
-
Ascentage Pharma Group Inc.Merck Sharp & Dohme LLCRecruitingMelanoma | P53 Mutation | Uveal Melanoma | Cutaneous Melanoma | Mucosal Melanoma | Malignant Peripheral Nerve Sheath Tumors | MPNST | Unresectable or Metastatic Melanoma or Advanced Solid Tumors | MDM2 Gene MutationUnited States, Australia
Clinical Trials on ONCOS-102
-
Targovax OyAgenus Inc.Withdrawn
-
Targovax OyCompleted
-
SOTIO a.s.TerminatedCastration-resistant Prostate CancerCzechia
-
Neothetics, IncCompleted
-
CinDome Pharma, Inc.CompletedGastroparesisUnited States
-
Orion Corporation, Orion PharmaCompleted
-
Tranzyme, Inc.CompletedDiabetes Mellitus, Type 2 | Diabetes Mellitus, Type 1 | GastroparesisUnited States, Belgium, Denmark, Finland, Germany, Norway, Poland, Sweden
-
Conceptra Biosciences, LLCRecruitingEarly Pregnancy Loss, Delayed Pregnancy LossUnited States
-
Taro Pharmaceuticals USACompleted
-
AmtixBio Co., Ltd.Not yet recruiting