This is a Phase 1 open-label, multicenter study of the safety and tolerability, immunogenic effects, antitumor activity, and pharmacodynamics of SQZ-AAC-HPV as monotherapy and in combination with immune checkpoint inhibitors in HLA-A\*02+ patients with recurrent, locally advanced or metastatic human papillomavirus strain 16 positive (HPV16+) solid tumors. The study includes patients with anal, rectal, cervical, head and neck, penile, vulvar, or vaginal cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Activating antigen carriers (AACs) cell therapy; therapeutic vaccine engineered from red blood cells manufactured with immunogenic epitopes of HPV16
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody
Programmed cell death 1 (PD-1) blocking antibody
City of Hope Medical Center
Duarte, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States
Number of participants with treatment-emergent adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0
For SQZ-AAC-HPV administered as monotherapy, and in combination with immune checkpoint inhibitors (Part 1 and Part 2, respectively)
Time frame: Up to 1 year after LPFV (Last Patient, First Visit)
Number of participants with dose-limiting toxicity (DLT)
For SQZ-AAC-HPV as a monotherapy (Part 1)
Time frame: Through Day 28
Number of participants with DLT
For SQC-AAC-HPV in combination with immune checkpoint inhibitors (Part 2)
Time frame: Through Day 28
Progression-free survival (PFS)
Defined as the time from first dose of study treatment to first overall response of PD by RECIST v 1.1 or to death by any cause. This will be censored at the last RECIST v1.1 assessment if PD/death is not observed. For SQZ-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).
Time frame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
Overall survival (OS)
Defined as the time from first dose of study treatment to death by any cause. This will be censored at the last date patient is known to be alive if death is not observed. For SQZ-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).
Time frame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
Objective response rate (ORR)
Proportion of patients with best response of complete response \[CR\] and/or partial response \[PR\] as defined by RECIST v1.1 criteria. For SQZ-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).
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Icahn School of Medicine at Mount Sinai
New York, New York, United States
Oregon Health & Science University
Portland, Oregon, United States
Time frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Duration of Response (DoR)
Defined as the time from overall response of CR or PR to first overall response of PD by RECIST v1.1 or to death by any cause. This is defined only for patients who have a CR or PR and will be censored at the last RECIST v1.1 assessment if PD/Death is not observed. For SQZ-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).
Time frame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
Best overall Response (BoR)
Evaluation of the BoR defined as CR, PR, Stable Disease \[SD\], Progressive Disease \[PD\] or Not Evaluable \[NE\] as defined by RECIST v1.1 criteria. For SQZ-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).
Time frame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
Disease-control rate (DCR)
Proportion of patients with best response of CR or PR or SD as defined by RECIST v1.1 criteria. For SQZ-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).
Time frame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
Amount of investigational product (IP) from individual patient blood collection - batch yield
To determine manufacturing feasibility as assessed by batch yield (number of manufacturing runs) (Part 1)
Time frame: From leukapheresis through manufacture, a maximum of 28 days
Amount of investigational product (IP) from individual patient blood collection - product failures
To determine manufacturing feasibility as assessed by number of product failures (Part 1)
Time frame: From leukapheresis through manufacture, a maximum of 28 days