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

Conditions

Adult Solid Tumor

Keywords

recurrent cancer, metastatic, locally advanced, cancer, cervical, head and neck, anal, penile, SQZ-PBMC-HPV, atezolizumab, HPV16, APC, cell therapy, ipilimumab, nivolumab, checkpoint inhibitors, immunotherapy, solid tumor, HLA-A*02, therapeutic vaccine, advanced solid tumor, rectal, vulvar, vaginal, PBMC, human papillomavirus strain 16, peripheral blood mononuclear cells, antigen presenting cells

Brief summary

This is a Phase 1 open-label, multicenter study of the safety and tolerability, immunogenic effects, antitumor activity, and pharmacodynamics of SQZ-PBMC-HPV as monotherapy and in combination with atezolizumab or other immune checkpoint inhibitors in HLA-A\*02+ patients with recurrent, locally advanced or metastatic human papillomavirus strain 16 positive (HPV16+) solid tumors. The study includes patients with anal, rectal, cervical, head and neck, penile, vulvar, or vaginal cancer.

Alice N. Weaver, Wade T. Iams, Jong Chul Park, Monica Mita, Udo Holtick et al. (19 authors)

Molecular Carcinogenesis2024-05-025 citations

10.1002/mc.23738

594 SQZ-PBMC-HPV-101: Increased overall survival in a subset of patients with recurrent, locally advanced, or metastatic HPV16<sup>+</sup>tumors treated with cell-based vaccine, SQZ-PBMC-HPV

Antonio Jimeno, Wade T. Iams, Jong‐Chul Park, Monica MitaSc, Udo Holtick et al. (16 authors)

Regular and Young Investigator Award Abstracts2023-10-31

10.1136/jitc-2023-sitc2023.0594

183P COMMANDER-001: Initial safety data from a phase I/II dose escalation/expansion study of SQZ-eAPC-HPV, a cell-based mRNA therapeutic cancer vaccine for HPV16+ solid tumors

Justin C. Moser, M. Pelster, A. Jimeno, J.C. Park, W.T. Iams et al. (15 authors)

Immuno-Oncology Technology2022-12-012 citations

10.1016/j.iotech.2022.100295

Initial results of a first-in-human, dose escalation study of a cell-based vaccine in HLA A*02+ patients (pts) with recurrent, locally advanced or metastatic HPV16+ solid tumors: SQZ-PBMC-HPV-101.

Antonio Jimeno, Joaquina Baranda, Monica Mita, Michael S. Gordon, Matthew H. Taylor et al. (14 authors)

Journal of Clinical Oncology2021-05-206 citations

10.1200/jco.2021.39.15_suppl.2536

418 A phase 1, dose escalation and dose expansion study of SQZ PBMC HPV as monotherapy and in combination with atezolizumab in HLA-A*02+ Patients with HPV16+ recurrent, or metastatic solid tumors

Cathy Eng, Joaquina Baranda, Matthew Taylor, Michael S. Gordon, Ursula A. Matulonis et al. (11 authors)

Regular and Young Investigator Award Abstracts2020-11-01

10.1136/jitc-2020-sitc2020.0418

Interventions

BIOLOGICALSQZ-PBMC-HPV

antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16

DRUGAtezolizumab

programmed cell death ligand 1 (PD-L1) blocking antibody

DRUGIpilimumab

cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody

DRUGNivolumab

programmed cell death 1 (PD-1) blocking antibody

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

Key Inclusion Criteria: * Male or female patients ≥18 years of age who are HLA-A\*02+ (performed during screening locally or centrally, or based on documented historic test results) * Histologically confirmed incurable or metastatic solid tumors that are HPV16+ (performed during screening locally or centrally, or based on documented historic test results) * Cancer must have progressed after at least 1 available standard therapy for incurable disease, or the patient is intolerant to or refuses standard therapy(ies) or has a tumor for which no standard therapy(ies) exist * 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 Baseline and on Cycle 2 Day 8 (+/- 3 days) * Patients must agree to venous access for the 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 the leukapheresis

Exclusion criteria

* Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to leukapheresis. For prior therapies with a half-life longer than 3 days, discontinuation of the therapy must have occurred at least 28 days 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 may not be eligible and should be discussed with the Sponsor * 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 neuropathy, ototoxicity, mucositis, fatigue, alopecia, or endocrine disorders managed with hormone replacement * Known active hepatitis B or hepatitis C, or active mycobacterium tuberculosis infection * History of any Grade 3 immune-related AE (irAE) from prior immunotherapy * Has known active central nervous system metastases * History of interstitial lung disease requiring steroids * Major surgery within 2 weeks of leukapheresis

Design outcomes

Primary

Measure	Time frame	Description
Overall survival (OS) [Part 3]	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-PBMC-HPV as a single agent (Part 3 only)
Number of participants with treatment-related 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-PBMC-HPV as a single agent (Part 1 and Part 3) and in combination with immune checkpoint inhibitors (Part 2)
Number of participants with dose-limiting toxicity (DLT)	Up to 1 year after LPFV	For SQZ-PBMC-HPV as a single agent (Part 1 and Part 3) and in combination with immune checkpoint inhibitors (Part 2)
Objective response rate (ORR) [Part 3]	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-PBMC-HPV as a single agent (Part 3 only)
Best overall response (BoR) [Part 3]	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-PBMC-HPV as a single agent (Part 3 only)
Progression-free survival (PFS) [Part 3]	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-PBMC-HPV as a single agent (Part 3 only)
Duration of Response (DoR) [Part 3]	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-PBMC-HPV as a single agent (Part 3 only)
Disease-control rate (DCR) [Part 3]	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-PBMC-HPV as a single agent (Part 3 only)

Secondary

Measure	Time frame	Description
Best overall response (BoR) [Part 1 and 2]	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-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)
Progression-free survival (PFS) [Part 1 and 2]	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-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)
Duration of Response (DoR) [Part 1 and 2]	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-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)
Disease-control rate (DCR) [Part 1 and 2]	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-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)
Overall survival (OS) [Part 1 and 2]	Through study completion, up to 2 years	For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)
Amount of investigational product (IP) from individual patient blood collection [Part 1]	From leukapheresis through manufacture, a maximum of 28 days	To determine manufacturing feasibility (Part 1 only)
Objective response rate (ORR) [Part 1 and 2]	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-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

Countries

Canada, Germany, United States

Outcome results

None listed