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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 9, 2023

Interventions

  • 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

Arms, Groups and Cohorts

  • 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
  • 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
  • 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

Clinical Trial Outcome Measures

Primary Measures

  • 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)

Secondary Measures

  • 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)

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • SQZ Biotechnologies
  • Provider of Information About this Clinical Study
    • Sponsor

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