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

A Phase 1, Multicenter, Open-Label Study of SQZ-AAC-HPV as Monotherapy and in Combination With Immune Checkpoint Inhibitors in HLA-A*02+ Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors

This is a Phase 1 open-label, multicenter study of the safety and tolerability, immunogenic effects, antitumor activity, and pharmacodynamics of SQZ-AAC-HPV as monotherapy and in combination with 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 Overview

• Status: Terminated
• Conditions: Adult Solid Tumor
• Intervention / Treatment: Biological: SQZ-AAC-HPV; Drug: Ipilimumab; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

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

Description

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 blood collection for manufacture of autologous blood product 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 of blood collection for manufacture of autologous blood product

Exclusion Criteria:

• Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to blood collection for manufacture of autologous blood product. For prior therapies with a half-life longer than 3 days, discontinuation of the therapy must have occurred at least 28 days prior to Cycle 1 Day 1
• Systemic treatment with either corticosteroids (>10 mg of prednisone or the equivalent per day) or other immunosuppressive medications within 14 days prior to Cycle 1 Day 1
• 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 blood collection for manufacture of autologous blood product, except Grade 2 alopecia
• Known active hepatitis B or hepatitis C, or active mycobacterium tuberculosis infection
• History of any Grade 4 immune-related AE (irAE) from prior immunotherapy
• Has known active central nervous system metastases
• History of interstitial lung disease requiring steroids
• Significant acute or chronic illness
• Major surgery within 2 weeks of blood collection for manufacture of autologous blood product

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Monotherapy Dose Escalation Phase; In Part 1, SQZ-AAC-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 1a: low dose SQZ-AAC-HPV; Cohort 1b: high dose SQZ-AAC-HPV; Cohort 1c: higher or lower dose SQZ-AAC-HPV	Biological: SQZ-AAC-HPV; Activating antigen carriers (AACs) cell therapy; therapeutic vaccine engineered from red blood cells manufactured with immunogenic epitopes of HPV16
Experimental: Part 2 Combination Safety Phase; In Part 2, SQZ-AAC-HPV in combination with immune checkpoint inhibitors (1) ipilimumab, (2) nivolumab, or (3) nivolumab plus ipilimumab is administered every 3 weeks up to a year, but the immune checkpoint inhibitors may be administered up to 2 years. There are 3 groups ("Cohorts") in this Phase as follows: Cohort 2a: SQZ-AAC-HPV RP2D (Recommended Phase 2 Dose) plus ipilimumab; Cohort 2b: SQZ-AAC-HPV RP2D plus nivolumab; Cohort 2c: SQZ-AAC-HPV RP2D plus nivolumab and ipilimumab	Biological: SQZ-AAC-HPV; Activating antigen carriers (AACs) cell therapy; therapeutic vaccine engineered from red blood cells manufactured with immunogenic epitopes of HPV16; Drug: Ipilimumab; Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody; Drug: Nivolumab; 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-AAC-HPV administered as monotherapy, and in combination with immune checkpoint inhibitors (Part 1 and Part 2, respectively)	Up to 1 year after LPFV (Last Patient, First Visit)
Number of participants with dose-limiting toxicity (DLT)	For SQZ-AAC-HPV as a monotherapy (Part 1)	Through Day 28
Number of participants with DLT	For SQC-AAC-HPV in combination with immune checkpoint inhibitors (Part 2)	Through Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).	Through start of a new anticancer therapy, up to 2 years after the 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-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).	Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
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-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, 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-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).	Through start of a new anticancer therapy, up to 2 years after the 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-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).	Through start of a new anticancer therapy, up to 2 years after the 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-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).	Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product
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) (Part 1)	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 (Part 1)	From leukapheresis through manufacture, a maximum of 28 days

Collaborators and Investigators

• Sponsor: SQZ Biotechnologies

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2021
• Primary Completion (Actual): November 2, 2023
• Study Completion (Actual): November 2, 2023

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: May 13, 2021
• First Posted (Actual): May 19, 2021

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; solid tumor; metastatic; nivolumab; advanced solid tumor; HPV16; head and neck; checkpoint inhibitors; ipilimumab; recurrent cancer; locally advanced; cervical; penile; therapeutic vaccine; anal; HLA-A*02; AAC; solid tumors cancer; SQZ-AAC-HPV
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: SQZ-AAC-HPV-101

Drug and device information, study documents

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