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

• ClinicalTrials.gov Identifier: NCT04084951
• Recruitment Status: Completed
• First Posted: September 10, 2019
• Last Update Posted: April 14, 2023
• Sponsor: SQZ Biotechnologies
• Information provided by (Responsible Party): SQZ Biotechnologies

Tracking Information

• First Submitted Date: September 1, 2019
• First Posted Date: September 10, 2019
• Last Update Posted Date: April 14, 2023
• Actual Study Start Date: January 28, 2020
• Actual Primary Completion Date: February 9, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 29, 2022)

• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)

Original Primary Outcome Measures (submitted: September 7, 2019)

• Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0 [ Time Frame: approximately 10 months ]
  For SQZ-PBMC-HPV as a single agent and in combination with atezolizumab
• Maximum tolerated dose (MTD) [ Time Frame: approximately 6 weeks ]
  MTD of SQZ-PBMC-HPV as a single agent and in combination with atezolizumab
• Recommended Phase 2 dose (RP2D) [ Time Frame: approximately 10 months ]
  RP2D of SQZ-PBMC-HPV as a single agent and in combination with atezolizumab

Current Secondary Outcome Measures (submitted: April 29, 2022)

• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)

Original Secondary Outcome Measures (submitted: September 7, 2019)

• Number of patients with development of endogenous immune responses via ELISPOT in CD8 T cells [ Time Frame: Up to 1 year ]
  Immunogenic effects on peripheral blood cells of SQZ-PBMC-HPV as a single agent and in combination with atezolizumab
• Antitumor activity [ Time Frame: Up to 1 year ]
  Tumor assessments using RECIST 1.1 of SQZ PBMC-HPV monotherapy and in combination with atezolizumab
• Number of patients with change in blood cytokine levels [ Time Frame: Up to 1 year ]
  SQZ-PBMC-HPV as a single agent and in combination with atezolizumab

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of SQZ-PBMC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Adult Solid Tumor

Intervention

• 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

Study Arms

• 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
  Intervention: Biological: SQZ-PBMC-HPV
• 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
  Interventions:

  • Biological: SQZ-PBMC-HPV
  • Drug: Atezolizumab
  • Drug: Ipilimumab
  • Drug: Nivolumab
• 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
  Intervention: Biological: SQZ-PBMC-HPV

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 12, 2023): 30
• Original Estimated Enrollment (submitted: September 7, 2019): 200
• Actual Study Completion Date: February 9, 2023
• Actual Primary Completion Date: February 9, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Male or female patients ≥18 years of age who are HLA-A*02+ (performed during screening locally or centrally, or based on documented historic test results)
• Histologically confirmed incurable or metastatic solid tumors that are HPV16+ (performed during screening locally or centrally, or based on documented historic test results)
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, United States

Administrative Information

• NCT Number: NCT04084951
• Other Study ID Numbers: SQZ-PBMC-HPV-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: SQZ Biotechnologies
• Original Responsible Party: Same as current
• Current Study Sponsor: SQZ Biotechnologies
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: SQZ Biotechnologies
• Verification Date: April 2023