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

SQZ Biotechnologies30 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Adult Solid Tumor

Interventions

SQZ-PBMC-HPVBIOLOGICAL

antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16

AtezolizumabDRUG

programmed cell death ligand 1 (PD-L1) blocking antibody

IpilimumabDRUG

cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (12)

HonorHealth

Scottsdale, Arizona, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

University of Colorado Anschutz Cancer Pavillion

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Number of participants with treatment-related adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0

For SQZ-PBMC-HPV as a single agent (Part 1 and Part 3) and in combination with immune checkpoint inhibitors (Part 2)

Time frame: Through 6 weeks after the patient's last dose of investigational product

Number of participants with dose-limiting toxicity (DLT)

For SQZ-PBMC-HPV as a single agent (Part 1 and Part 3) and in combination with immune checkpoint inhibitors (Part 2)

Time frame: Up to 1 year after LPFV

Objective response rate (ORR) [Part 3]

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)

Time frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product

Best overall response (BoR) [Part 3]

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)

Time frame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product]

Progression-free survival (PFS) [Part 3]

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)

Time frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product

Duration of Response (DoR) [Part 3]

Data from ClinicalTrials.gov

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Secondary Outcomes

Objective response rate (ORR) [Part 1 and 2]

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)

Time frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product

Best overall response (BoR) [Part 1 and 2]

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)

Time frame: Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product]

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

Duration of Response (DoR) [Part 1 and 2]

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)

Time frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product

Disease-control rate (DCR) [Part 1 and 2]

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)

Time frame: Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product

Overall survival (OS) [Part 1 and 2]

For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

Time frame: Through study completion, up to 2 years

Amount of investigational product (IP) from individual patient blood collection [Part 1]

To determine manufacturing feasibility (Part 1 only)

Time frame: From leukapheresis through manufacture, a maximum of 28 days