This study is being conducted to explore the immunological mechanism of action of Peptide-coated Conditionally Replicating Adenovirus-1 (PeptiCRAd-1) plus Checkpoint inhibitor (CPI) therapy in multiple cancer types, as well as to obtain early information on the safety of this combination therapy.
This is a Phase I, open-label, non-randomized, first-in-human study. All patients will be pre-treated with a low dose of intravenous (i.v.) Cyclophosphamide (CPO) followed by monotherapy doses of PeptiCRAd-1. PeptiCRAd-1 will be administered by intratumoral (i.t.) injection (Cohort 1) and by i.t. and subcutaneous (s.c.) injection (Cohort 2) followed by combination therapy with PeptiCRAd-1 and i.v. CPI (pembrolizumab).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
All patients will receive PeptiCRAd-1.
All patients will be pre-treated with one single dose of Cyclophosphamide.
All patients will receive 6 doses of Pembrolizumab within the study.
Krankenhaus Nordwest
Frankfurt, Germany
National Center for Tumor Diseases
Heidelberg, Germany
Universitätsklinikum Tübingen
Tübingen, Germany
Measurement of Safety and tolerability indexes (Incidence of TEAEs, SAEs and DLTs as assessed by CTCAE version 5.0 and changes in assessed safety parameters) for PeptiCRAd-1 monotherapy.
The incidence and characteristics of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs) will be assessed by CTCAE version 5.0 and changes from baseline in assessed safety parameters (Hematology tests, Clinical Chemistry safety tests, urine analysis ECOG/WHO performance status, vital signs) are measured in patients receiving PeptiCRAd-1 monotherapy in order to evaluate the safety and tolerability.
Time frame: From study protocol day 1 (baseline) until 1 month
Measurement of Safety and tolerability indexes (Incidence of TEAEs, SAEs and DLTs as assessed by CTCAE version 5.0 and changes in assessed safety parameters) for PeptiCRAd-1 and CPI combination.
The incidence and characteristics of TEAEs, SAEs and DLTs will be assessed by CTCAE version 5.0 and changes from baseline in assessed safety parameters (Hematology tests, Clinical Chemistry safety tests, urine analysis ECOG/WHO performance status, vital signs) are measured in patients receiving PeptiCRAd-1 and CPI combination in order to evaluate the safety and tolerability.
Time frame: From first month through study completion, an average of 4.5 months.
Measurement of New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) and Melanoma-associated antigen 3 (MAGE A3) specific T-cells in peripheral blood.
Presence vs. no presence of cellular immune response.
Time frame: Change from Baseline through study completion, an average of 5 months.
Measurement of NY-ESO-1 and MAGE A3 antibodies in serum.
Presence vs. no presence of humoral response.
Time frame: Change from Baseline to an average of 3,5 months
To determine the number of tumor infiltrating lymphocytes (TILs) in tumor mass.
Number of TILs in tumor biopsies.
Time frame: Change from Baseline to an average of 3 months
To determine objective response rate (ORR).
Objective responses according to RECIST 1.1, iRECIST, itRECIST and PERCIST 1.0.
Time frame: Change from Baseline through study completion, an average of 5 months.
To determine overall survival.
Overall survival presented in Kaplan-Meier plot.
Time frame: Change from Baseline through study completion, an average of 5 months.
Correlation between immune activation in peripheral blood and tumor mass and clinical outcome.
Correlation between immune activation (immunological variables) in peripheral blood and tumor mass and clinical outcome (ORR, OS).
Time frame: Change from Baseline through study completion, an average of 5 months.
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