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

NCT04892043 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: SQZ-AAC-HPV-101
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Adult Solid Tumor

Keywords

solid tumors cancer; metastatic; locally advanced; cancer; cervical; head and neck; anal; penile; SQZ-AAC-HPV; HPV16; AAC; cell therapy; ipilimumab; nivolumab; checkpoint inhibitors; immunotherapy; solid tumor; HLA-A*02; therapeutic vaccine; recurrent cancer; advanced solid tumor

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Progression-free survival (PFS)

  Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product

• Overall survival (OS)

  Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product

• Objective response rate (ORR)

  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)

  Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product

• Best overall Response (BoR)

  Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product

Study Arms (2)

Part 1 Monotherapy Dose Escalation Phase

EXPERIMENTAL

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

Part 2 Combination Safety Phase

EXPERIMENTAL

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; Drug: Ipilimumab; Drug: Nivolumab

Interventions

SQZ-AAC-HPV BIOLOGICAL

Activating antigen carriers (AACs) cell therapy; therapeutic vaccine engineered from red blood cells manufactured with immunogenic epitopes of HPV16

Part 1 Monotherapy Dose Escalation Phase; Part 2 Combination Safety Phase

Ipilimumab DRUG

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody

Part 2 Combination Safety Phase

Nivolumab DRUG

Programmed cell death 1 (PD-1) blocking antibody

Part 2 Combination Safety Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• SQZ Biotechnologies: lead

Study Sites (6)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms; Recurrence

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: May 19, 2021
• Study Start: August 19, 2021
• Primary Completion: November 2, 2023
• Study Completion: November 2, 2023
• Last Updated: February 23, 2024

Record last verified: 2024-02

Locations

US (6)