Clinical Trials /

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

NCT04084951

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: SQZ-PBMC-HPV-101
  • NCT ID: NCT04084951

Conditions

  • Adult Solid Tumor

Interventions

DrugSynonymsArms
SQZ-PBMC-HPVPart 1 Monotherapy Dose Escalation Phase
AtezolizumabPart 2 Combination Safety Phase
IpilimumabPart 2 Combination Safety Phase
NivolumabPart 2 Combination Safety Phase

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part 1 Monotherapy Dose Escalation PhaseExperimentalIn Part 1, SQZ-PBMC-HPV as a monotherapy is administered every 3 weeks for up to a year. There are at least 3 groups ("Cohorts") in this Phase as follows: Cohort 1: low dose SQZ-PBMC-HPV Cohort 2: high dose SQZ-PBMC-HPV Cohort 3: high dose SQZ-PBMC-HPV double-priming
  • SQZ-PBMC-HPV
Part 2 Combination Safety PhaseExperimentalIn 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
  • SQZ-PBMC-HPV
  • Atezolizumab
  • Ipilimumab
  • Nivolumab
Part 3 Monotherapy Dose Expansion PhaseExperimentalIn 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
  • SQZ-PBMC-HPV

Eligibility 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 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 leukapheresis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0
Time Frame:Up to 1 year after LPFV (Last Patient, First Visit)
Safety Issue:
Description:For SQZ-PBMC-HPV as a single agent and in combination with immune checkpoint inhibitors

Secondary Outcome Measures

Measure:Antitumor activity (Parts 1 and 2)
Time Frame:Up to 1 year after LPFV
Safety Issue:
Description:Tumor assessments using RECIST 1.1 of SQZ PBMC-HPV monotherapy and in combination with immune checkpoint inhibitors
Measure:Manufacturing feasibility (Part 1 only)
Time Frame:Up to 3 months after LPFV
Safety Issue:
Description:Individual patient batch yields

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:SQZ Biotechnologies

Trial Keywords

  • Solid tumors 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

Last Updated

July 23, 2021