Adult Solid Tumor
Conditions
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
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.
Interventions
BIOLOGICALSQZ-eAPC-HPV
Enhanced antigen presenting cells (eAPC) cell therapy; therapeutic vaccine engineered from autologous peripheral blood mononuclear cells (PBMCs) by incorporating 5 mRNAs.
BIOLOGICALPembrolizumab
programmed cell death 1 (PD-1) blocking antibody
Sponsors
SQZ Biotechnologies
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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+ (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| Number of participants with dose-limiting toxicity (DLT) | Through Day 28 | For SQZ-eAPC-HPV as a monotherapy (Part 1A). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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). |
| 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). |
| 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) |
| 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 |
| 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). |
| 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). |
Countries
United States
Outcome results
None listed