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

SQZ Biotechnologies

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Adult Solid Tumor

Treatments: Biological: Pembrolizumab; Biological: SQZ-eAPC-HPV

Study type: Interventional

Funder types: Industry

Identifiers

NCT05357898

COMMANDER-001

Details and patient eligibility

About

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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria - All Patients:

• 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

Inclusion Criteria - Part 2:

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

Exclusion Criteria - All Patients:

• 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

Exclusion Criteria - Part 1B:

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

Exclusion Criteria - Part 2:

• Prior treatment with an immune check-point inhibitor

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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20 participants in 3 patient groups

Part 1A Monotherapy Dose Escalation Phase

Experimental group

Description:

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.

Treatment:

Biological: SQZ-eAPC-HPV

Part 1B Combination Phase

Experimental group

Description:

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.

Treatment:

Biological: SQZ-eAPC-HPV

Biological: Pembrolizumab

Part 2 Lead-in Combination Phase

Experimental group

Description:

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.

Treatment:

Biological: SQZ-eAPC-HPV

Biological: Pembrolizumab