Study of SQZ-AAC-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 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04892043
• Other study ID #: SQZ-AAC-HPV-101
• Status: Terminated
• Phase: Phase 1
• Start date: August 19, 2021
• Est. completion date: November 2, 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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: November 2, 2023
• Est. primary completion date: November 2, 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 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

Related Conditions & MeSH terms

• Adult Solid Tumor
• Neoplasms

Intervention

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
• Nivolumab
Programmed cell death 1 (PD-1) blocking antibody

Locations

Country	Name	City	State
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Medical Center	Duarte	California
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Oregon Health & Science University	Portland	Oregon

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-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)
Primary	Number of participants with dose-limiting toxicity (DLT)	For SQZ-AAC-HPV as a monotherapy (Part 1)	Through Day 28
Primary	Number of participants with DLT	For SQC-AAC-HPV in combination with immune checkpoint inhibitors (Part 2)	Through Day 28
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-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
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-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
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-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
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-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
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-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
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-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
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) (Part 1)	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 (Part 1)	From leukapheresis through manufacture, a maximum of 28 days