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

Adult Solid Tumor Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT04084951
• Other study ID #: SQZ-PBMC-HPV-101
• Status: Completed
• Phase: Phase 1
• Start date: January 28, 2020
• Est. completion date: February 9, 2023

Study information

• Verified date: April 2023
• Source: SQZ Biotechnologies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 9, 2023
• Est. primary completion date: February 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adult Solid Tumor
• Neoplasms

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
• Ipilimumab
cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody
• Nivolumab
programmed cell death 1 (PD-1) blocking antibody

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Germany	University Hospital Cologne, Clinic I for Internal Medicine	Cologne
United States	University of Colorado Anschutz Cancer Pavillion	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	The Masonic Cancer Center University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Providence Cancer Institute	Portland	Oregon
United States	HonorHealth	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
SQZ Biotechnologies

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Through 6 weeks after the patient's last dose of investigational product
Primary	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)	Up to 1 year after LPFV
Primary	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)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Primary	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)	Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product]
Primary	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)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Primary	Duration of Response (DoR) [Part 3]	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)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Primary	Disease-control rate (DCR) [Part 3]	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)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Primary	Overall survival (OS) [Part 3]	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)	Through study completion, up to 2 years
Secondary	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)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Secondary	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)	Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product]
Secondary	Progression-free survival (PFS) [Part 1 and 2]	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)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Secondary	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)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Secondary	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)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Secondary	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)	Through study completion, up to 2 years
Secondary	Amount of investigational product (IP) from individual patient blood collection [Part 1]	To determine manufacturing feasibility (Part 1 only)	From leukapheresis through manufacture, a maximum of 28 days