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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

NCT03003676

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief 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 Programmed Cell Death Protein 1 (PD1) Blockade
  • 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

Clinical Trial IDs

  • ORG STUDY ID: ONCOS C824
  • NCT ID: NCT03003676

Conditions

  • Advanced or Unresectable Melanoma Progressing After PD1 Blockade

Interventions

DrugSynonymsArms
ONCOS-102Experimental: ONCOS-102+cyclophosphamide+pembrolizumab
CyclophosphamideExperimental: ONCOS-102+cyclophosphamide+pembrolizumab
PembrolizumabExperimental: ONCOS-102+cyclophosphamide+pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Experimental: ONCOS-102+cyclophosphamide+pembrolizumabExperimentalPart 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).
  • ONCOS-102
  • Cyclophosphamide
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Adults 18 years of age or older.

          -  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.

          -  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.

          -  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.

        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.

          -  Receipt of Investigational agents within 28 days prior to first dose of protocol
             therapy.

          -  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.

          -  Women who are pregnant or breast-feeding currently or are planning to conceive during
             or up to 4 months after end of protocol therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent adverse events including treatment-emergent serious adverse events assessed by CTCAE.
Time Frame:6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective response rates by RECIST 1.1 and irRECIST.
Time Frame:6 months
Safety Issue:
Description:
Measure:Changes in immune cell subsets in tumor tissue before and after ONCOS-102 and pembrolizumab.
Time Frame:6 months
Safety Issue:
Description:
Measure:Changes in immune cell subsets in peripheral blood before and after ONCOS-102 and pembrolizumab.
Time Frame:6 months
Safety Issue:
Description:
Measure:Correlation of Tumour Infiltrating Lymphocytes (TILs) and Overall Response Rate (ORR).
Time Frame:6 months
Safety Issue:
Description:
Measure:Progression Free Survival (PFS) assessed by RECIST 1.1 and irRECIST.
Time Frame:6 months
Safety Issue:
Description:
Measure:Clinical benefit rate, defined as any confirmed objective response by RECIST 1.1 or stable disease.
Time Frame:6 months
Safety Issue:
Description:
Measure:Clinical benefit rate, defined as any objective response by irRECIST criteria or immune-related stable disease.
Time Frame:6 months
Safety Issue:
Description:
Measure:Change in size in individual lesions.
Time Frame:6 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Targovax Oy

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