Clinical trial NCT04892043: Study of SQZ-AAC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors
Official title: A Phase 1, Multicenter, Open-Label Study of SQZ-AAC-HPV as Monotherapy and in Combination With Immune Checkpoint Inhibitors in HLA-A*02+ Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Adult Solid Tumor
Keywords: solid tumors cancer
metastatic
locally advanced
cancer
cervical
head and neck
anal
penile
SQZ-AAC-HPV
HPV16
AAC
cell therapy
ipilimumab
nivolumab
checkpoint inhibitors
immunotherapy
solid tumor
HLA-A*02
therapeutic vaccine
recurrent cancer
advanced solid tumor
Lead sponsor: SQZ Biotechnologies
Sponsor class: INDUSTRY
First posted: 2021-05-19
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Key Inclusion Criteria:

* Male or female patients ≥18 years of age who are HLA-A\*02+ (performed during screening locally or centrally, or based on documented historic test results)
* Histologically confirmed incurable or metastatic solid tumors that are HPV16+ (performed during screening locally or centrally, or based on documented historic test results)
* Cancer must have progressed after at least 1 available standard therapy for incurable disease, or the patient is intolerant to or refuses standard therapy(ies) or has a tumor for which no standard therapy(ies) exist
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
* At least 1 measurable lesion according to RECIST 1.1
* Must have a lesion that can be biopsied with acceptable clinical risk and agree to have a fresh biopsy at Baseline and on Cycle 2 Day 8 (+/- 3 days)
* Patients must agree to venous access for the blood collection for manufacture of autologous blood product and be willing to have a central line inserted if venous access is an issue
* Adequate organ function and bone marrow reserve performed within 14 days of blood collection for manufacture of autologous blood product

Exclusion Criteria:

* Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to blood collection for manufacture of autologous blood product. For prior therapies with a half-life longer than 3 days, discontinuation of the therapy must have occurred at least 28 days prior to Cycle 1 Day 1
* Systemic treatment with either corticosteroids (\>10 mg of prednisone or the equivalent per day) or other immunosuppressive medications within 14 days prior to Cycle 1 Day 1
* Patients treated with non-corticosteroid based immunosuppressive agents within the last 6 months may not be eligible and should be discussed with the Sponsor
* Patients with active, known, or suspected autoimmune disease may not be eligible and should be discussed with the Sponsor
* Patients with \>Grade 1 AEs related to previous treatment with anticancer or investigational therapy that do not resolve at least 2 weeks prior to blood collection for manufacture of autologous blood product, except Grade 2 alopecia
* Known active hepatitis B or hepatitis C, or active mycobacterium tuberculosis infection
* History of any Grade 4 immune-related AE (irAE) from prior immunotherapy
* Has known active central nervous system metastases
* History of interstitial lung disease requiring steroids
* Significant acute or chronic illness
* Major surgery within 2 weeks of blood collection for manufacture of autologous blood product

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0
timeFrame: Up to 1 year after LPFV (Last Patient, First Visit)
measure: Number of participants with dose-limiting toxicity (DLT)
timeFrame: Through Day 28
measure: Number of participants with DLT
timeFrame: Through Day 28
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
measure: Overall survival (OS)
timeFrame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
measure: Objective response rate (ORR)
timeFrame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
measure: Duration of Response (DoR)
timeFrame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
measure: Best overall Response (BoR)
timeFrame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
measure: Disease-control rate (DCR)
timeFrame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
measure: Amount of investigational product (IP) from individual patient blood collection - batch yield
timeFrame: From leukapheresis through manufacture, a maximum of 28 days
measure: Amount of investigational product (IP) from individual patient blood collection - product failures
timeFrame: From leukapheresis through manufacture, a maximum of 28 days
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
References: