Study of SQZ-PBMC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors

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

  • Adult Solid Tumor

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

Vanderbilt University Medical Center
Nashville, Tennessee 37212
Contact:
Clinical Trials Information Program
800-811-8480
CIP@vumc.org

More Details

Status
Recruiting
Sponsor
SQZ Biotechnologies

Study Contact

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