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

NCT05357898 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: COMMANDER-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 9

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

Keywords

recurrent cancer; metastatic; locally advanced; cancer; head and neck cancer; cervical; anal; vulvar; penile; SQZ-eAPC-HPV; HPV16; human papillomavirus 16; eAPC; enhanced antigen presenting cells; cell therapy; pembrolizumab; checkpoint inhibitors; immunotherapy; solid tumor; therapeutic vaccine; advanced solid tumor; throat cancer

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-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 Outcomes (8)

• 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

• Best overall response (BoR)

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

• Progression-free survival (PFS)

  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 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)

  Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product

Study Arms (3)

Part 1A Monotherapy Dose Escalation Phase

EXPERIMENTAL

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

Part 1B Combination Phase

EXPERIMENTAL

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; Biological: Pembrolizumab

Part 2 Lead-in Combination Phase

EXPERIMENTAL

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; Biological: Pembrolizumab

Interventions

SQZ-eAPC-HPV BIOLOGICAL

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

Part 1A Monotherapy Dose Escalation Phase; Part 1B Combination Phase; Part 2 Lead-in Combination Phase

Pembrolizumab BIOLOGICAL

programmed cell death 1 (PD-1) blocking antibody

Part 1B Combination Phase; Part 2 Lead-in Combination 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• SQZ Biotechnologies: lead

Study Sites (9)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of Colorado Anschutz Cancer Pavillion

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-6840, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

MeSH Terms

Conditions

Recurrence; Neoplasm Metastasis; Neoplasms; Head and Neck Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

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 18, 2022
• First Posted: May 3, 2022
• Study Start: March 24, 2022
• Primary Completion: November 27, 2023
• Study Completion: November 27, 2023
• Last Updated: February 23, 2024

Record last verified: 2024-02

Locations

US (9)