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

Adult Solid Tumor Clinical Trial

Official title:

A Phase 1/2, First-in-Human, Multicenter, Open-Label Study of SQZ-eAPC-HPV as Monotherapy and in Combination With Immune Checkpoint Inhibitor(s) in Patients With HPV16+ Recurrent, Locally Advanced, or Metastatic Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05357898
• Other study ID #: COMMANDER-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 24, 2022
• Est. completion date: November 27, 2023

Study information

• Verified date: February 2024
• Source: SQZ Biotechnologies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/2, first-in-human, open label, multicenter study to assess safety and tolerability, antitumor activity, and immunogenic and pharmacodynamic effects of SQZ-eAPC-HPV as monotherapy and in combination with pembrolizumab in patients with recurrent, locally advanced, or metastatic HPV16+ solid tumors. The study includes patients with head and neck, cervical, anal, vulvar, or penile cancer.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: November 27, 2023
• Est. primary completion date: November 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria - All Patients:

• Male or female patients =18 years of age
• Histologically confirmed incurable or metastatic solid tumors that are HPV16+ (performed during screening locally or centrally, or based on documented historic test results)
• 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 Screening and on Cycle 2 Day 8 (+/- 2 days)
• Patients must agree to venous access for 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 leukapheresis

Inclusion Criteria - Part 2:

• Patients must not have been treated with immune check-point inhibitors

Exclusion Criteria - All Patients:

• Treatment with anticancer therapy, including investigational therapy, within 2 weeks 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 prior to leukapheresis
• 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 neuropathy, ototoxicity, mucositis, fatigue, alopecia, or endocrine disorders managed with hormone replacement
• Known HIV infection, active hepatitis B or hepatitis C, or active mycobacterium tuberculosis infection
• Has known active central nervous system metastases
• Have active interstitial lung disease and any history of myocarditis
• Major surgery within 2 weeks of leukapheresis

Exclusion Criteria - Part 1B:

• Known hypersensitivity to pembrolizumab
• History of any Grade 3 immune-related AE (irAE) from prior immunotherapy

Exclusion Criteria - Part 2:

• Prior treatment with an immune check-point inhibitor

Related Conditions & MeSH terms

• Adult Solid Tumor
• Neoplasms

Intervention

Biological:
• SQZ-eAPC-HPV
Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.
• Pembrolizumab
programmed cell death 1 (PD-1) blocking antibody

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Cancer Pavillion	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	City of Hope Medical Center	Duarte	California
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Honor Health Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
SQZ Biotechnologies

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-emergent adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0	For SQZ-eAPC-HPV as a monotherapy, in combination with pembrolizumab, and as a monotherapy lead-in with pembrolizumab (Part 1A, Part 1B, and Part 2, respectively).	Through 6 weeks after the patient's last dose of investigational product
Primary	Number of participants with dose-limiting toxicity (DLT)	For SQZ-eAPC-HPV as a monotherapy (Part 1A).	Through Day 28
Primary	Number of participants with dose-limiting toxicity (DLT)	For SQZ-eAPC-HPV in combination with pembrolizumab (Part 1B).	Through Day 42
Secondary	Objective response rate (ORR)	Proportion of patients with best response of complete response [CR] and/or partial response [PR] as defined by RECIST v1.1 criteria. For SQZ-eAPC-HPV as a monotherapy, in combination with pembrolizumab, and as a monotherapy lead-in with pembrolizumab (Part 1A, Part 1B, and Part 2, respectively).	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)	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-eAPC-HPV as a monotherapy, in combination with pembrolizumab, and as a monotherapy lead-in with pembrolizumab (Part 1A, Part 1B, and Part 2, respectively).	Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
Secondary	Progression-free survival (PFS)	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-eAPC-HPV as a monotherapy, in combination with pembrolizumab, and as a monotherapy lead-in with pembrolizumab (Part 1A, Part 1B, and Part 2, respectively).	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)	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-eAPC-HPV as a monotherapy, in combination with pembrolizumab, and as a monotherapy lead-in with pembrolizumab (Part 1A, Part 1B, and Part 2, respectively).	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)	Proportion of patients with best response of CR or PR or SD as defined by RECIST v1.1 criteria. For SQZ-eAPC-HPV as a monotherapy, in combination with pembrolizumab, and as a monotherapy lead-in with pembrolizumab (Part 1A, Part 1B, and Part 2, respectively).	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)	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-eAPC-HPV as a monotherapy, in combination with pembrolizumab, and as a monotherapy lead-in with pembrolizumab (Part 1A, Part 1B, and Part 2, respectively).	Through study completion, up to 2 years
Secondary	Amount of investigational product (IP) from individual patient blood collection - batch yield	To determine manufacturing feasibility as assessed by batch yield (number of manufacturing runs)	From leukapheresis through manufacture, a maximum of 28 days
Secondary	Amount of investigational product (IP) from individual patient blood collection - product failures	To determine manufacturing feasibility as assessed by number of product failures	From leukapheresis through manufacture, a maximum of 28 days