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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 : May 16, 2022
Sponsor:
Information provided by (Responsible Party):
SQZ Biotechnologies

Study Description
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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

Study Design
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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


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1 Monotherapy Dose Escalation Phase

In Part 1, SQZ-PBMC-HPV as a monotherapy is administered on Day 1 of every 3 week cycles for up to a year. In Cohort 3 (double-priming), SQZ-PBMC-HPV is also administered on Day 2 of Cycle 1. There are at least 3 groups ("Cohorts") in this Phase as follows:

  • Cohort 1: specified dose SQZ-PBMC-HPV
  • Cohort 2: specified dose SQZ-PBMC-HPV
  • Cohort 3: specified 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


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0 [ Time Frame: Through 6 weeks after the patient's last dose of investigational product ]
    For SQZ-PBMC-HPV as a single agent (Part 1 and Part 3) and in combination with immune checkpoint inhibitors (Part 2)

  2. Number of participants with dose-limiting toxicity (DLT) [ Time Frame: Up to 1 year after LPFV ]
    For SQZ-PBMC-HPV as a single agent (Part 1 and Part 3) and in combination with immune checkpoint inhibitors (Part 2)

  3. Objective response rate (ORR) [Part 3] [ Time Frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product ]
    Proportion of patients with best response of complete response [CR] and/or partial response [PR] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 3 only)

  4. Best overall response (BoR) [Part 3] [ Time Frame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product] ]
    Evaluation of the BoR defined as CR, PR, Stable Disease [SD], Progressive Disease [PD] or Not Evaluable [NE] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 3 only)

  5. Progression-free survival (PFS) [Part 3] [ Time Frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product ]
    Defined as the time from first dose of study treatment to first overall response of PD by RECIST v 1.1 or to death by any cause. This will be censored at the last RECIST v1.1 assessment if PD/death is not observed. For SQZ-PBMC-HPV as a single agent (Part 3 only)

  6. Duration of Response (DoR) [Part 3] [ Time Frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product ]
    Defined as the time from overall response of CR or PR to first overall response of PD by RECIST v1.1 or to death by any cause. This is defined only for patients who have a CR or PR and will be censored at the last RECIST v1.1 assessment if PD/Death is not observed. For SQZ-PBMC-HPV as a single agent (Part 3 only)

  7. Disease-control rate (DCR) [Part 3] [ Time Frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product ]
    Proportion of patients with best response of CR or PR or SD as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 3 only)

  8. Overall survival (OS) [Part 3] [ Time Frame: Through study completion, up to 2 years ]
    Defined as the time from first dose of study treatment to death by any cause. This will be censored at the last date patient is known to be alive if death is not observed. For SQZ-PBMC-HPV as a single agent (Part 3 only)


Secondary Outcome Measures :
  1. Objective response rate (ORR) [Part 1 and 2] [ Time Frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product ]
    Proportion of patients with best response of complete response [CR] and/or partial response [PR] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

  2. Best overall response (BoR) [Part 1 and 2] [ Time Frame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product] ]
    Evaluation of the BoR defined as CR, PR, Stable Disease [SD], Progressive Disease [PD] or Not Evaluable [NE] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

  3. Progression-free survival (PFS) [Part 1 and 2] [ Time Frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product ]
    Defined as the time from first dose of study treatment to first overall response of PD by RECIST v 1.1 or to death by any cause. This will be censored at the last RECIST v1.1 assessment if PD/death is not observed. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

  4. Duration of Response (DoR) [Part 1 and 2] [ Time Frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product ]
    Defined as the time from overall response of CR or PR to first overall response of PD by RECIST v1.1 or to death by any cause. This is defined only for patients who have a CR or PR and will be censored at the last RECIST v1.1 assessment if PD/Death is not observed. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

  5. Disease-control rate (DCR) [Part 1 and 2] [ Time Frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product ]
    Proportion of patients with best response of CR or PR or SD as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

  6. Overall survival (OS) [Part 1 and 2] [ Time Frame: Through study completion, up to 2 years ]
    For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

  7. Amount of investigational product (IP) from individual patient blood collection [Part 1] [ Time Frame: From leukapheresis through manufacture, a maximum of 28 days ]
    To determine manufacturing feasibility (Part 1 only)


Eligibility Criteria
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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 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
Contacts and Locations
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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 patientadvocacy@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: Jazmin Garcia       Jazmin.Garcia@cshs.org   
Contact: Sabrina Mir       Sabrina.Mir@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, Minnesota
The Masonic Cancer Center University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Cancer Information Nurse Line    612-624-2620    ccinfo@umn.edu   
Principal Investigator: Naomi Fujioka, 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, Oklahoma
OU Health Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Silas Day    405-271-8001    Silas-Day@ouhsc.edu   
Principal Investigator: Adam Asch, MD         
United States, Oregon
Providence Cancer Institute Active, not recruiting
Portland, Oregon, United States, 97213
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         
Germany
University Hospital Cologne, Clinic I for Internal Medicine Recruiting
Cologne, Germany, 50937
Contact: Josette Mc Kenzie    +49 221 478-76636    josette.mc-kenzie@uk-koeln.de   
Principal Investigator: Udo Holtick, MD         
Sponsors and Collaborators
SQZ Biotechnologies
More Information
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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: May 16, 2022
Last Verified: May 2022

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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:
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
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