Phase 1, non-randomized, open label dose escalation clinical trial evaluating the safety of GEN2 in participants with primary \& metastatic liver tumors.
This clinical trial will be divided into two phases: Phase IA in which the dose, route, and schedule of the GEN2 administration is determined and Phase IB which is designed to explore the activity of GEN2 in patients of a defined or several defined tumor types and stages based on the Phase IA data of GEN2. Phase IA is divided into three routes of administration: (a) Phase 1A.1 which explores peripheral IV infusion; (b) Phase IA.2 which investigates hepatic arterial infusion and (c) Phase IA.3 which examines intratumoral delivery.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
61
GEN2 is an investigational drug combining cytotoxic and immunotherapy.
Makati Medical Center
Makati City, Philippines
The Medical City
Pasig, Philippines
National Kidney and Transplant Institute
Quezon City, Philippines
St. Luke's Medical Center
Quezon City, Philippines
Maximum Tolerated Dose (MTD)
The MTD is the defined as the highest dose level at which, at most, one patient experiences a DLT.
Time frame: First 3 weeks of GEN2 Administration
Dose Limiting Toxicity (DLT)
* Grade 4 neutropenia * Grade 4 thrombocytopenia; * Grade 3 or greater nausea and/or vomiting despite the use of adequate/maximal medical intervention and/or prophylaxis; * Any Grade 3 or greater non-hematological toxicity (except Grade 3 injection site reaction, alopecia, fatigue); * Retreatment delay of more than 3 weeks due to delayed recovery from a toxicity related to treatment with GEN2; * Grade 3 or greater allergic (hypersensitivity) reaction despite the appropriate use of premedications (defined within the CTC as "Prolonged" (e.g., not rapidly reponsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates).
Time frame: First 3 weeks of GEN2 Administration
Recommended Phase 2 Dose (RP2D)
The RP2D will be administered for Phase 1B. It is determined when the accelerated phase ends for Phase IA and the dose assignment for a new patient in the standard dose escalation will follow a modified Fibonacci scheme. If a modified Fibonacci has already been used, the RP2D will be explored from the remaining intervals between the dose which had no DLTs and the Maximum Administered Dose (MAD).
Time frame: First 3 weeks of GEN2 Administration
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Each Adverse Event is to be classified by the Investigator as serious or non-serious. The classification of the gravity of the event determines the reporting procedures to be followed.
Time frame: Treatment Initiation until 30 days after last dose of GEN2
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Plasma pharmacokinetics of GEN2
GEN2 PK Cmax is dose proportional.
Time frame: During Week 1 of Cycle 1, Cycle 2 & Cycle 6 (each cycle is 28 days)
HSV-TK-m2 protein expression from GEN2 via serial [18F]FHBG PET and/or SPECT imaging
Identify number of participants with positive \[18F\] FHBG scan
Time frame: Day 3-8 of GEN2 Treatment
Preliminary Evidence of anti-tumor activity of GEN2
Measure of anti-tumor efficacy based on objective tumor assessments made according to the irRECIST 1.1
Time frame: Week 9 and every 6 weeks thereafter through study completion, an average of 8 months.
Clinical research testing for antibodies to retrovector gp70 env, replication-competent retrovirus in peripheral blood lymphocytes (PBLs); vector integration into genomic DNA of PBLs, and circulating hGM-CSF protein
No replication-competent retrovirus. No vector integration into genomic DNA of PBLS. No GM-CSF detectable in patients after GEN2 administration
Time frame: Cycle 1, Cycle 2, Cycle 6, after 6th month on treatment, annually thereafter