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

• Sponsor: SQZ Biotechnologies (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05357898
• Collaborator: (none)
• Enrollment: 60
• Locations: 3
• Arms: 3
• Anticipated Duration (Months): 24
• Patients Per Site: 20
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adult Solid Tumor	Biological: SQZ-eAPC-HPV; Biological: Pembrolizumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, First-in-Human, Multicenter, Open-Label Study of SQZ-eAPC-HPV as Monotherapy and in Combination With Immune Checkpoint Inhibitor(s) in Patients With HPV16+ Recurrent, Locally Advanced, or Metastatic Solid Tumors
• Actual Study Start Date: Mar 24, 2022
• Anticipated Primary Completion Date: Mar 24, 2024
• Anticipated Study Completion Date: Mar 24, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: SQZ-eAPC-HPV; Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.
Experimental: 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.	Biological: SQZ-eAPC-HPV; Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.; Biological: Pembrolizumab; programmed cell death 1 (PD-1) blocking antibody
Experimental: 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.	Biological: SQZ-eAPC-HPV; Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.; Biological: Pembrolizumab; programmed cell death 1 (PD-1) blocking antibody

Outcome Measures

Primary Outcome Measures

1. Number of participants with treatment-emergent adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0 [Through 6 weeks after the patient's last dose of investigational product]

   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).

2. Number of participants with dose-limiting toxicity (DLT) [Through Day 28]

   For SQZ-eAPC-HPV as a monotherapy (Part 1A).

3. Number of participants with dose-limiting toxicity (DLT) [Through Day 42]

   For SQZ-eAPC-HPV in combination with pembrolizumab (Part 1B).

Secondary Outcome Measures

1. 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]

   Proportion of patients with best response of complete response [CR] and/or partial response [PR] as defined by RECIST v1.1 criteria. 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).

2. Best overall response (BoR) [Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product]

   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-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).

3. 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]

   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-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).

4. 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]

   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-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).

5. 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]

   Proportion of patients with best response of CR or PR or SD as defined by RECIST v1.1 criteria. 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).

6. Overall survival (OS) [Through study completion, up to 2 years]

   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-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).

7. Amount of investigational product (IP) from individual patient blood collection - batch yield [From leukapheresis through manufacture, a maximum of 28 days]

   To determine manufacturing feasibility as assessed by batch yield (number of manufacturing runs)

8. Amount of investigational product (IP) from individual patient blood collection - product failures [From leukapheresis through manufacture, a maximum of 28 days]

   To determine manufacturing feasibility as assessed by number of product failures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria - All Patients:

• Male or female patients ≥18 years of age

• Histologically confirmed incurable or metastatic solid tumors that are HPV16+

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Honor Health Research Institute	Scottsdale	Arizona	United States	85258
2	University of Colorado Anschutz Cancer Pavillion	Aurora	Colorado	United States	80045
3	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• SQZ Biotechnologies

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: SQZ Biotechnologies
• ClinicalTrials.gov Identifier: NCT05357898
• Other Study ID Numbers: COMMANDER-001
• First Posted: May 3, 2022
• Last Update Posted: Jun 3, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by SQZ Biotechnologies: 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
• Additional relevant MeSH terms: Neoplasms; Pembrolizumab

Study Results

No Results Posted as of Jun 3, 2022