This is a Phase 1/2a, open-label, study to evaluate the safety and preliminary efficacy of intratumoral T3011 given alone and in combination with intravenous pembrolizumab in partients with advanced or metastatic solid tumors.
This is a Phase 1/2a, open-label, first-in-human study of T3011 given via intratumoral (IT) injection as a single agent and in combination with IV pembrolizumab in participants with advanced or metastatic solid tumors. The Phase 1 portion of the study is a single agent dose escalation which will use a 3+3 design to evaluate escalating doses of T3011. Total enrollment will depend on the toxicities and/or activity observed, with approximately 15 to 30 evaluable participants enrolled. Once the RP2D is established Phase 2a Part 1 will enroll approximately 10 participants with locally recurrent or metastatic melanoma (in Arm A) 23 to 53 participants with HNSCC in Arm B, 40 to 80 participants with sarcoma in Arm C and 10 participants with cSCC in Arm D. During Phase 2a Part 1 the safety, tolerability, and preliminary efficacy of T3011 as a single agent will be evaluated. Phase 2a Part 2 will enroll in parallel to Phase 2a Part 1 once the RP2D is established. The safety, tolerability, and preliminary efficacy of IT T3011 given in combination with IV pembrolizumab will be evaluated in 15 participants with histologically or pathologically confirmed metastatic NSCLC (Arm E). A rollover arm is also included in this study to allow participants who have documented progression on T3011 alone to receive T3011 in combination with pembrolizumab if considered eligible.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
T3011 will be administered up to 4mL as an intratumoral injection given Q2W.
T3011 will be administered up to 4mL as an intratumoral injection in combination with intravenous pembrolizumab given Q3W.
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
COMPLETEDMassachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGDana Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGUniversity of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
RECRUITINGMary Crowley Cancer Research
Dallas, Texas, United States
RECRUITINGVirginia Cancer Specialists
Fairfax, Virginia, United States
RECRUITINGSouthern Oncology
Bedford Park, Australia
RECRUITINGPeninsula & South Eastern Haematology and Oncology Group
Frankston, Australia
RECRUITINGThe Alfred
Melbourne, Australia
RECRUITINGSafety and tolerability of escalating doses T3011
Number of participants in dose escalating cohorts with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.
Time frame: Up to 2 years from first dose of T3011
To determine the dose(s) of T3011 to be examined in Phase 2a
Incidence of DLTs
Time frame: Through the first two T3011 injections (approximately 28 days)
Safety and tolerability of T3011 dose(s) selected from Phase 1 in disease specific cohorts
Number of participants with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.
Time frame: Up to 2 years from first dose of T3011
Characterize the safety and tolerability of T3011 in combination with pembrolizumab
Number of participants with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.
Time frame: Up to 2 years from first dose of T3011
Characterize the safety and tolerability of T3011 in combination with pembrolizumab in participants who progress on T3011 alone
Number of participants with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.
Time frame: Up to 2 years from first dose of T3011
Overall response rate (ORR)
ORR is defined as the proportion of participants who have a partial response (PR) or complete response (CR) to intervention, based on assessments by RECIST v1.1 and iRECIST.
Time frame: Up to 2 years from first dose of T3011
Disease control rate (DCR)
DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments by RECIST v1.1 and iRECIST.
Time frame: Up to 2 years from first dose of T3011
Duration of response (DOR)
DOR is defined as the time from the first met CR or PR until disease progression or death due to any cause, whichever occurs first.
Time frame: Up to 2 years from first dose of T3011
Durable response (DR)
DR is defined as objective response (CR or PR) according to RECIST v1.1 and iRECIST.
Time frame: Up to 2 years from first dose of T3011
Progression-free survival (PFS)
PFS is defined as the time from enrollment to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first per RECIST v1.1 and iRECIST.
Time frame: Up to 2 years from first dose of T3011
Overall Survival (OS)
OS is defined as the time from enrollment to death from any cause.
Time frame: Up to 1 year after last dose of T3011
Presence of neutralizing antibodies of anti-PD-1 antibody for antidrug antibodies (ADAs) development
To evaluate the immunogenicity of anti-PD-1 antibody expressed by T3011 given as single agent and in combination with pembrolizumab post injection.
Time frame: Up to 2 years from first dose of T3011
Presence and frequency of T3011 in injection site swab, saliva, and urine
To evaluate the virus shedding of T3011 following intratumoral injection
Time frame: Up to 2 years from first dose of T3011
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