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

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ClinicalTrials.gov Identifier: NCT04892043
Recruitment Status : Recruiting
First Posted : May 19, 2021
Last Update Posted : September 1, 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-AAC-HPV as monotherapy and in combination with 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-AAC-HPV Drug: Ipilimumab Drug: Nivolumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Open-Label Study of SQZ-AAC-HPV as Monotherapy and in Combination With Immune Checkpoint Inhibitors in HLA-A*02+ Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors
Actual Study Start Date : August 19, 2021
Estimated Primary Completion Date : April 15, 2024
Estimated Study Completion Date : April 15, 2024

Resource links provided by the National Library of Medicine


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

In Part 1, SQZ-AAC-HPV as a monotherapy is administered every 3 weeks for up to a year.

There are 3 groups ("Cohorts") in this Phase as follows:

  • Cohort 1a: low dose SQZ-AAC-HPV
  • Cohort 1b: intermediate dose SQZ-AAC-HPV
  • Cohort 1c: high dose SQZ-AAC-HPV
Biological: SQZ-AAC-HPV
activating antigen carriers (AACs) cell therapy; therapeutic vaccine engineered from red blood cells manufactured with immunogenic epitopes of HPV16

Experimental: Part 2 Combination Safety Phase

In Part 2, SQZ-AAC-HPV in combination with immune checkpoint inhibitors (1) ipilimumab, (2) nivolumab, or (3) nivolumab plus ipilimumab is administered every 3 weeks up to a year, but the immune checkpoint inhibitors may be administered up to 2 years. There are 3 groups ("Cohorts") in this Phase as follows:

  • Cohort 2a: SQZ-AAC-HPV RP2D (Recommended Phase 2 Dose) plus ipilimumab
  • Cohort 2b: SQZ-AAC-HPV RP2D plus nivolumab
  • Cohort 2c: SQZ-AAC-HPV RP2D plus nivolumab and ipilimumab
Biological: SQZ-AAC-HPV
activating antigen carriers (AACs) cell therapy; therapeutic vaccine engineered from red blood cells manufactured with immunogenic epitopes of HPV16

Drug: Ipilimumab
cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody

Drug: Nivolumab
programmed cell death 1 (PD-1) blocking antibody




Primary Outcome Measures :
  1. Number of patients with treatment-related adverse events according to NCI CTCAE version 5.0 [ Time Frame: Up to 1 year after LPFV (Last Patient, First Visit) ]
    To determine the RP2D and to characterize the safety and tolerability of SQZ-AAC-HPV administered as monotherapy (Part 1), and in combination with checkpoint inhibitors (Part 2)


Secondary Outcome Measures :
  1. Change in tumor size compared with baseline using RECIST 1.1 and iRECIST [ Time Frame: Up to 1 year after LPFV ]
    To determine antitumor activity (Part 1 and 2) of SQZ-AAC-HPV monotherapy and in combination with checkpoint inhibitors

  2. Number of potential doses from individual patient blood collection [ Time Frame: Up to 3 months after LPFV ]
    To determine manufacturing feasibility (Part 1 only)


Other Outcome Measures:
  1. Changes in cytokine levels compared with baseline [ Time Frame: Up to 1 year after LPFV ]
    To explore changes in blood cytokines after treatment with SQZ-AAC-HPV (Part 1 and 2)

  2. Changes in T cell infiltration in the tumor micro-environment as assessed by paired biopsy [ Time Frame: Up to 1 year after LPFV ]
    To characterize the immunogenic and pharmacodynamic effects (on selected pharmacodynamic parameters) and duration of pharmacodynamic response following SQZ-AAC-HPV administration (Part 1 and 2)



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 blood draw 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 blood draw

Exclusion Criteria:

  • Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to blood draw. For prior therapies with a half-life longer than 3 days, discontinuation of the therapy must have occurred at least 28 days prior to Cycle 1 Day 1
  • Systemic treatment with either corticosteroids (>10 mg of prednisone or the equivalent per day) or other immunosuppressive medications within 14 days prior to Cycle 1 Day 1
  • 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 blood draw, 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 blood draw

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): NCT04892043


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

Locations
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United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Jessica Guido    858-534-0254    jeguido@health.ucsd.edu   
Principal Investigator: Sandip Patel, MD         
Sponsors and Collaborators
SQZ Biotechnologies
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Responsible Party: SQZ Biotechnologies
ClinicalTrials.gov Identifier: NCT04892043    
Other Study ID Numbers: SQZ-AAC-HPV-101
First Posted: May 19, 2021    Key Record Dates
Last Update Posted: September 1, 2021
Last Verified: August 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-AAC-HPV
HPV16
AAC
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
Antineoplastic Agents, Immunological
Antineoplastic Agents