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

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

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.

Study Overview

• Status: Terminated
• Conditions: Adult Solid Tumor
• Intervention / Treatment: Biological: SQZ-eAPC-HPV; Biological: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Honor Health Research Institute
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Cancer Pavillion
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6840
      • University of Nebraska Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A Monotherapy Dose Escalation Phase; In Part 1A, SQZ-eAPC-HPV as a monotherapy is administered every 3 weeks for up to a year. There are 3 groups ("Cohorts") in this Phase as follows: Cohort 1: low dose SQZ-eAPC-HPV; Cohort 2: intermediate dose SQZ-eAPC-HPV; Cohort 3: high dose SQZ-eAPC-HPV Additional provisional cohorts may be opened prior to starting Part 1B.	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.
Experimental: Part 1B Combination Phase; In Part 1B, SQZ-eAPC-HPV is administered in combination with immune checkpoint inhibitor pembrolizumab. SQZ-eAPC-HPV will be administered on Day 1 of Cycle 1 and 200 mg of pembrolizumab will be administered on Day 8 of Cycle 1. In future cycles, patients will be first administered SQZ-eAPC-HPV and then pembrolizumab on the first day of each cycle, every 3 weeks for a maximum of 1 year for SQZ-eAPC-HPV, and 2 years for pembrolizumab.	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.; Biological: Pembrolizumab; programmed cell death 1 (PD-1) blocking antibody
Experimental: Part 2 Lead-in Combination Phase; In Part 2, SQZ-eAPC-HPV will be administered on Day 1 of each treatment cycle. Treatment with 200 mg of pembrolizumab will begin in Cycle 3. Starting at Cycle 3, patients will be administered SQZ-eAPC-HPV and then pembrolizumab every 3 weeks for a maximum of 1 year for SQZ-eAPC-HPV, and 2 years for pembrolizumab.	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.; Biological: Pembrolizumab; programmed cell death 1 (PD-1) blocking antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Number of participants with dose-limiting toxicity (DLT)	For SQZ-eAPC-HPV as a monotherapy (Part 1A).	Through Day 28
Number of participants with dose-limiting toxicity (DLT)	For SQZ-eAPC-HPV in combination with pembrolizumab (Part 1B).	Through Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: SQZ Biotechnologies

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2022
• Primary Completion (Actual): November 27, 2023
• Study Completion (Actual): November 27, 2023

Study Registration Dates

• First Submitted: April 18, 2022
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (Actual): May 3, 2022

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; cancer; cell therapy; head and neck cancer; solid tumor; metastatic; pembrolizumab; advanced solid tumor; HPV16; checkpoint inhibitors; vulvar; recurrent cancer; locally advanced; cervical; penile; therapeutic vaccine; anal; SQZ-eAPC-HPV; human papillomavirus 16; eAPC; enhanced antigen presenting cells; throat cancer
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: COMMANDER-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No