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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Adult Solid Tumor

Intervention / Treatment
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* Biological: SQZ-eAPC-HPV
* Biological: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A Monotherapy Dose Escalation Phase<br>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<br>* Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.<br>|
| Experimental: Part 1B Combination Phase<br>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<br>* Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.<br>Biological: Pembrolizumab<br>* programmed cell death 1 (PD-1) blocking antibody<br>|
| Experimental: Part 2 Lead-in Combination Phase<br>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<br>* Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.<br>Biological: Pembrolizumab<br>* programmed cell death 1 (PD-1) blocking antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | 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). | 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) | 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). | Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product | 
| Progression-free survival (PFS) | 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). | 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) | 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). | 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) | 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). | Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product | 
| Overall survival (OS) | 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). | Through study completion, up to 2 years | 
| Amount of investigational product (IP) from individual patient blood collection - batch yield | To determine manufacturing feasibility as assessed by batch yield (number of manufacturing runs) | From leukapheresis through manufacture, a maximum of 28 days | 
| Amount of investigational product (IP) from individual patient blood collection - product failures | To determine manufacturing feasibility as assessed by number of product failures | From leukapheresis through manufacture, a maximum of 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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