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

NCT ID: NCT05357898

Last Updated: 2024-02-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-24
• Study Completion Date: 2023-11-27

Brief 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.

Conditions

Adult Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

SQZ-eAPC-HPV

Intervention Type: BIOLOGICAL

Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.

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.

Group Type: EXPERIMENTAL

SQZ-eAPC-HPV

Intervention Type: BIOLOGICAL

Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.

Pembrolizumab

Intervention Type: BIOLOGICAL

programmed cell death 1 (PD-1) blocking antibody

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.

Group Type: EXPERIMENTAL

SQZ-eAPC-HPV

Intervention Type: BIOLOGICAL

Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.

Pembrolizumab

Intervention Type: BIOLOGICAL

programmed cell death 1 (PD-1) blocking antibody

Interventions

SQZ-eAPC-HPV

Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.

Intervention Type: BIOLOGICAL

Pembrolizumab

programmed cell death 1 (PD-1) blocking antibody

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

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

Exclusion Criteria

• 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

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

• Prior treatment with an immune check-point inhibitor

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SQZ Biotechnologies

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Honor Health Research Institute

Scottsdale, Arizona, United States

City of Hope Medical Center

Duarte, California, United States

University of Colorado Anschutz Cancer Pavillion

Aurora, Colorado, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

COMMANDER-001

Identifier Type: -

Identifier Source: org_study_id