Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Male or female patients ≥18 years of age who are HLA-A*02+ - Histologically confirmed incurable or metastatic solid tumors that are HPV16+ - 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 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 leukapheresis

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1 Monotherapy Dose Escalation Phase
In Part 1, SQZ-PBMC-HPV as a monotherapy is administered every 3 weeks for up to a year. There are at least 3 groups ("Cohorts") in this Phase as follows: Cohort 1: low dose SQZ-PBMC-HPV Cohort 2: high dose SQZ-PBMC-HPV Cohort 3: high dose SQZ-PBMC-HPV double-priming
  • Biological: SQZ-PBMC-HPV
    antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16
Experimental
Part 2 Combination Safety Phase
In Part 2, SQZ-PBMC-HPV in combination with immune checkpoint inhibitors (1) atezolizumab, (2) ipilimumab, (3) nivolumab, or (4) nivolumab and ipilimumab, is administered every 3 weeks for up to a year except atezolizumab may be given up to 2 years; and ipilimumab will be administered four times (in a timeframe less than a year) if safety allows. There are 4 groups ("Cohorts") in this Phase as follows: Cohort 4: SQZ-PBMC-HPV RP2D (Recommended Phase 2 Dose) plus atezolizumab Cohort 5: SQZ-PBMC-HPV RP2D plus ipilimumab Cohort 6: SQZ-PBMC-HPV RP2D plus nivolumab Cohort 7: SQZ-PBMC-HPV RP2D plus nivolumab and ipilimumab
  • Biological: SQZ-PBMC-HPV
    antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16
  • Drug: Atezolizumab
    programmed cell death ligand 1 (PD-L1) blocking antibody
  • Drug: Ipilimumab
    cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody
  • Drug: Nivolumab
    programmed cell death 1 (PD-1) blocking antibody
Experimental
Part 3 Monotherapy Dose Expansion Phase
In Part 3, SQZ-PBMC-HPV is administered at the RP2D to patients enrolled in HPV16+ cancer-type specific cohorts. There are 4 groups ("Cohorts") in this Phase as follows: Cohort 8: SQZ-PBMC-HPV RP2D in HPV16+ head and neck cancer patients Cohort 9: SQZ-PBMC-HPV RP2D in HPV16+ cervical cancer patients Cohort 10: SQZ-PBMC-HPV RP2D in HPV16+ anal cancer patients Cohort 11: SQZ-PBMC-HPV RP2D in other HPV16+ cancer patients
  • Biological: SQZ-PBMC-HPV
    antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16

Recruiting Locations

University of Kansas Cancer Center
Kansas City, Kansas 66160
Contact:
Jeff Roesgen
913-945-8679
jroesgen@kumc.edu

More Details

Status
Recruiting
Sponsor
SQZ Biotechnologies

Study Contact

Ricardo F. Zwirtes, MD
203-506-7253
PBMC-HPV-101@sqzbiotech.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.