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

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ClinicalTrials.gov Identifier: NCT04084951
Recruitment Status : Recruiting
First Posted : September 10, 2019
Last Update Posted : November 4, 2021
Sponsor:
Information provided by (Responsible Party):
SQZ Biotechnologies

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.

Condition or disease Intervention/treatment Phase
Adult Solid Tumor Biological: SQZ-PBMC-HPV Drug: Atezolizumab Drug: Ipilimumab Drug: Nivolumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 28, 2020
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0 [ Time Frame: Up to 1 year after LPFV (Last Patient, First Visit) ]
    For SQZ-PBMC-HPV as a single agent and in combination with immune checkpoint inhibitors

  2. Recommended Phase 2 dose (RP2D) [ Time Frame: Up to 1 year after LPFV ]
    RP2D of SQZ-PBMC-HPV as a single agent and in combination with immune checkpoint inhibitors

  3. Antitumor activity (Part 3 only) [ Time Frame: Up to 1 year after LPFV ]
    Tumor assessments using RECIST 1.1 of SQZ PBMC-HPV monotherapy


Secondary Outcome Measures :
  1. Antitumor activity (Parts 1 and 2) [ Time Frame: Up to 1 year after LPFV ]
    Tumor assessments using RECIST 1.1 of SQZ PBMC-HPV monotherapy and in combination with immune checkpoint inhibitors

  2. Manufacturing feasibility (Part 1 only) [ Time Frame: Up to 3 months after LPFV ]
    Individual patient batch yields


Other Outcome Measures:
  1. Number of patients with change in blood cytokine levels [ Time Frame: Up to 1 year after LPFV ]
    SQZ-PBMC-HPV as a single agent and in combination with immune checkpoint inhibitors

  2. Number of patients with development of endogenous immune responses as assessed by functional assay in CD8 T cells [ Time Frame: Up to 1 year after LPFV ]
    Immunogenic effects on peripheral blood cells of SQZ-PBMC-HPV as a single agent and in combination with immune checkpoint inhibitors



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04084951


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

Locations
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United States, Arizona
HonorHealth Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Joyce Schaffer    480-323-1364    clinicaltrials@honorhealth.com   
Principal Investigator: Michael S Gordon, MD         
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Kari Kayser, BSN, RN,CCRP    310-967-0694    kari.kayser@cshs.org   
Principal Investigator: Monica Mita, MD         
United States, Colorado
University of Colorado Anschutz Cancer Pavillion Recruiting
Aurora, Colorado, United States, 80045
Contact: Ana Nguyen    720-848-4394    ana.nguyen@cuanschutz.edu   
Principal Investigator: Antonio Jimeno, MD, PhD         
United States, Kansas
University of Kansas Cancer Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Jeff Roesgen    913-945-8679    jroesgen@kumc.edu   
Principal Investigator: Joaquina Baranda, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Betsy Valles, RN       bvalles@partners.org   
Principal Investigator: Jong Chul Park, MD         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-6840
Contact: Pamela Nielsen       pnielsen@nebraskamed.com   
Principal Investigator: Kerry Rodabaugh, MD         
United States, Oregon
Providence Cancer Institute Recruiting
Portland, Oregon, United States, 97213
Contact: Research Office    503-215-2614    canrsrchstudies@providence.org   
Principal Investigator: Matthew H Taylor, MD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37212
Contact: Clinical Trials Information Program    800-811-8480    CIP@vumc.org   
Principal Investigator: Wade Thomas Iams, MD         
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2C1
Contact: New Patient Referral Centre (NPRC)    416-946-4575      
Principal Investigator: Neesha Dhani, MD         
Sponsors and Collaborators
SQZ Biotechnologies
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Responsible Party: SQZ Biotechnologies
ClinicalTrials.gov Identifier: NCT04084951    
Other Study ID Numbers: SQZ-PBMC-HPV-101
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: November 4, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by SQZ Biotechnologies:
Solid tumors 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
Additional relevant MeSH terms:
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Neoplasms
Nivolumab
Ipilimumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action