Advanced or Unresectable Melanoma Progressing After PD1 Blockade Clinical Trial
Official title:
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
| Verified date | July 2021 |
| Source | Targovax ASA |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is a multi center, phase I pilot study of sequential ONCOS-102 and pembrolizumab in patients with advanced or unresectable melanoma progressing after PD1 blockade. The primary objective of the study is to determine the safety of sequential treatment with ONCOS-102 followed by pembrolizumab. The protocol aims to enroll patients into two cohorts: Part I: up to 12 patients will receive sequential treatment with ONCOS-102 followed by pembrolizumab. Part II: up to 12 patients will receive an initial treatment phase with ONCOS-102 followed by a treatment phase with ONCOS-102 in combination with pembrolizumab.
| Status | Completed |
| Enrollment | 21 |
| Est. completion date | October 2020 |
| Est. primary completion date | July 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Norway | Oslo University Hospital - The Norwegian Radium Hospital | Oslo | |
| United States | University of Maryland Comprehensive Cancer Center | Baltimore | Maryland |
| United States | Memorial Sloan Kettering Cancer Center | New York | New York |
| United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Targovax Oy |
United States, Norway,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Somatic Mutational Rate and Neoepitope Burden in Tumors and Explore Relationship to Response. | 6 months | ||
| Other | Changes in T Cell Receptor Clonality in Infiltrating and Circulating T Cells. | 6 months | ||
| Other | Gene Expression Changes in the Tumor Microenvironment and Peripheral Blood. | 6 months | ||
| Primary | Incidence of Treatment-emergent Adverse Events Including Treatment-emergent Serious Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE). | 6 months | ||
| Secondary | Objective Response Rates by RECIST 1.1 and irRECIST. | 6 months | ||
| Secondary | Changes in Immune Cell Subsets in Tumor Tissue Before and After ONCOS-102 and Pembrolizumab. | 6 months | ||
| Secondary | Changes in Immune Cell Subsets in Peripheral Blood Before and After ONCOS-102 and Pembrolizumab. | 6 months | ||
| Secondary | Correlation of Tumour Infiltrating Lymphocytes (TILs) and Overall Response Rate (ORR). | 6 months | ||
| Secondary | Progression Free Survival (PFS) Assessed by RECIST 1.1 and irRECIST. | 6 months | ||
| Secondary | Clinical Benefit Rate, Defined as Any Confirmed Objective Response by RECIST 1.1 or Stable Disease. | 6 months | ||
| Secondary | Clinical Benefit Rate, Defined as Any Objective Response by irRECIST Criteria or Immune-related Stable Disease. | 6 months | ||
| Secondary | Change in Size in Individual Lesions. | 6 months |