Trial | NCT04084951  Report issue

Title

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

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    30
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.
Study Started
Jan 28
2020
Primary Completion
Feb 09
2023
Study Completion
Feb 09
2023
Last Update
Apr 14
2023

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

Part 1 Monotherapy Dose Escalation Phase Experimental

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

Part 2 Combination Safety Phase Experimental

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

Part 3 Monotherapy Dose Expansion Phase Experimental

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

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
No Results Posted