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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04892043
Recruitment Status : Recruiting
First Posted : May 19, 2021
Last Update Posted : August 15, 2022
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: high dose SQZ-AAC-HPV
  • Cohort 1c: higher or lower 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 participants with treatment-emergent adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0 [ Time Frame: Up to 1 year after LPFV (Last Patient, First Visit) ]
    For SQZ-AAC-HPV administered as monotherapy, and in combination with immune checkpoint inhibitors (Part 1 and Part 2, respectively)

  2. Number of participants with dose-limiting toxicity (DLT) [ Time Frame: Through Day 28 ]
    For SQZ-AAC-HPV as a monotherapy (Part 1)

  3. Number of participants with DLT [ Time Frame: Through Day 28 ]
    For SQC-AAC-HPV in combination with immune checkpoint inhibitors (Part 2)


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Through start of a new anticancer therapy, up to 2 years after the 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-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  2. Overall survival (OS) [ Time Frame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product ]
    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-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  3. Objective response rate (ORR) [ 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-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  4. Duration of Response (DoR) [ Time Frame: Through start of a new anticancer therapy, up to 2 years after the 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-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  5. Best overall Response (BoR) [ 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-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  6. Disease-control rate (DCR) [ Time Frame: Through start of a new anticancer therapy, up to 2 years after the 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-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  7. Amount of investigational product (IP) from individual patient blood collection - batch yield [ Time Frame: From leukapheresis through manufacture, a maximum of 28 days ]
    To determine manufacturing feasibility as assessed by batch yield (number of manufacturing runs) (Part 1)

  8. Amount of investigational product (IP) from individual patient blood collection - product failures [ Time Frame: From leukapheresis through manufacture, a maximum of 28 days ]
    To determine manufacturing feasibility as assessed by number of product failures (Part 1)



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 collection for manufacture of autologous blood product 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 of blood collection for manufacture of autologous blood product

Exclusion Criteria:

  • Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to blood collection for manufacture of autologous blood product. 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 collection for manufacture of autologous blood product, 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 collection for manufacture of autologous blood product

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 patientadvocacy@sqzbiotech.com

Locations
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United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Victoria M Villaflor, MD    877-467-3411    vvillaflor@coh.org   
Principal Investigator: Victoria M Villaflor, MD         
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         
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Alexandra VanSlembrouck, BS, CCRP    313-576-9236    vanslema@karmanos.org   
Principal Investigator: Anthony Shields, MD, PhD         
United States, New York
Roswell Park Comprehensive Cancer Center Recruiting
Buffalo, New York, United States, 14263
Contact: Emese Zsiros, MD, PhD       emese.zsiros@roswellpark.org   
Principal Investigator: Emese Zsiros, MD, PhD         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Clinical Trials Information Line    503-494-1080    trials@ohsu.edu   
Principal Investigator: Richard T Maziarz, MD         
Spain
Clínica Universidad de Navarra Recruiting
Pamplona, Spain, 31008
Contact: Leyre R Eraul    948 25 54 00 ext 2732    leyreresano@unav.es   
Principal Investigator: Mariano Ponz Sarvise, MD, PhD         
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: August 15, 2022
Last Verified: August 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:
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
recurrent cancer
advanced solid tumor
Additional relevant MeSH terms:
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Neoplasms
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action