Clinical trial NCT04084951: Study of SQZ-PBMC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors
Official title: A Phase 1, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of SQZ-PBMC-HPV as Monotherapy and in Combination With Atezolizumab or Other Immune Checkpoint Inhibitors in HLA-A*02+ Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adult Solid Tumor
Keywords: recurrent cancer
metastatic
locally advanced
cancer
cervical
head and neck
anal
penile
SQZ-PBMC-HPV
atezolizumab
HPV16
APC
cell therapy
ipilimumab
nivolumab
checkpoint inhibitors
immunotherapy
solid tumor
HLA-A*02
therapeutic vaccine
advanced solid tumor
rectal
vulvar
vaginal
PBMC
human papillomavirus strain 16
peripheral blood mononuclear cells
antigen presenting cells
Lead sponsor: SQZ Biotechnologies
Sponsor class: INDUSTRY
First posted: 2019-09-10
Enrollment: 30
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-PBMC-HPV as monotherapy and in combination with atezolizumab or other 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 leukapheresis 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 prior to the leukapheresis

Exclusion Criteria:

* Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to leukapheresis. For prior therapies with a half-life longer than 3 days, discontinuation of the therapy must have occurred at least 28 days prior to leukapheresis
* Systemic treatment with either corticosteroids (\>10 mg of prednisone or the equivalent per day) or other immunosuppressive medications within 14 days prior to leukapheresis
* 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 leukapheresis, except neuropathy, ototoxicity, mucositis, fatigue, alopecia, or endocrine disorders managed with hormone replacement
* Known active hepatitis B or hepatitis C, or active mycobacterium tuberculosis infection
* History of any Grade 3 immune-related AE (irAE) from prior immunotherapy
* Has known active central nervous system metastases
* History of interstitial lung disease requiring steroids
* Major surgery within 2 weeks of leukapheresis

Primary outcomes:
measure: Number of participants with treatment-related adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0
timeFrame: Through 6 weeks after the patient's last dose of investigational product
measure: Number of participants with dose-limiting toxicity (DLT)
timeFrame: Up to 1 year after LPFV
measure: Objective response rate (ORR) [Part 3]
timeFrame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
measure: Best overall response (BoR) [Part 3]
timeFrame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product]
measure: Progression-free survival (PFS) [Part 3]
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) [Part 3]
timeFrame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
measure: Disease-control rate (DCR) [Part 3]
timeFrame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
measure: Overall survival (OS) [Part 3]
timeFrame: Through study completion, up to 2 years
Secondary outcomes:
measure: Objective response rate (ORR) [Part 1 and 2]
timeFrame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
measure: Best overall response (BoR) [Part 1 and 2]
timeFrame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product]
measure: Progression-free survival (PFS) [Part 1 and 2]
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) [Part 1 and 2]
timeFrame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
measure: Disease-control rate (DCR) [Part 1 and 2]
timeFrame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
measure: Overall survival (OS) [Part 1 and 2]
timeFrame: Through study completion, up to 2 years
measure: Amount of investigational product (IP) from individual patient blood collection [Part 1]
timeFrame: From leukapheresis through manufacture, a maximum of 28 days
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Cancer Pavillion
state: Colorado
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: The Masonic Cancer Center University of Minnesota
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Cologne
country: Germany
facility: University Hospital Cologne, Clinic I for Internal Medicine
Study officials:
References: