Study of SQZ-PBMC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04084951 |
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Recruitment Status :
Completed
First Posted : September 10, 2019
Last Update Posted : April 14, 2023
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Sponsor:
SQZ Biotechnologies
Information provided by (Responsible Party):
SQZ Biotechnologies
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Adult Solid Tumor | Biological: SQZ-PBMC-HPV Drug: Atezolizumab Drug: Ipilimumab Drug: Nivolumab | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 30 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of SQZ-PBMC-HPV as Monotherapy and in Combination With Atezolizumab or Other Immune Checkpoint Inhibitors in HLA-A*02+ Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors |
| Actual Study Start Date : | January 28, 2020 |
| Actual Primary Completion Date : | February 9, 2023 |
| Actual Study Completion Date : | February 9, 2023 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Atezolizumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part 1 Monotherapy Dose Escalation Phase
In Part 1, SQZ-PBMC-HPV as a monotherapy is administered on Day 1 of every 3 week cycles for up to a year. In Cohort 3 (double-priming), SQZ-PBMC-HPV is also administered on Day 2 of Cycle 1. There are at least 3 groups ("Cohorts") in this Phase as follows:
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Biological: SQZ-PBMC-HPV
antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16 |
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Experimental: Part 2 Combination Safety Phase
In Part 2, SQZ-PBMC-HPV in combination with immune checkpoint inhibitors (1) atezolizumab, (2) ipilimumab, (3) nivolumab, or (4) nivolumab and ipilimumab, is administered every 3 weeks for up to a year except atezolizumab may be given up to 2 years; and ipilimumab will be administered four times (in a timeframe less than a year) if safety allows. There are 4 groups ("Cohorts") in this Phase as follows:
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Biological: SQZ-PBMC-HPV
antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16 Drug: Atezolizumab programmed cell death ligand 1 (PD-L1) blocking antibody Drug: Ipilimumab cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody Drug: Nivolumab programmed cell death 1 (PD-1) blocking antibody |
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Experimental: Part 3 Monotherapy Dose Expansion Phase
In Part 3, SQZ-PBMC-HPV is administered at the RP2D to patients enrolled in HPV16+ cancer-type specific cohorts. There are 4 groups ("Cohorts") in this Phase as follows:
|
Biological: SQZ-PBMC-HPV
antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16 |
Primary Outcome Measures :
- Number of participants with treatment-related adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0 [ Time Frame: 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) [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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)
- Overall survival (OS) [Part 3] [ Time Frame: 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)
Secondary Outcome Measures :
- Objective response rate (ORR) [Part 1 and 2] [ Time Frame: 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)
- Best overall response (BoR) [Part 1 and 2] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: From leukapheresis through manufacture, a maximum of 28 days ]To determine manufacturing feasibility (Part 1 only)
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04084951
Locations
| United States, Arizona | |
| HonorHealth | |
| Scottsdale, Arizona, United States, 85258 | |
| United States, California | |
| Cedars-Sinai Medical Center | |
| Los Angeles, California, United States, 90048 | |
| United States, Colorado | |
| University of Colorado Anschutz Cancer Pavillion | |
| Aurora, Colorado, United States, 80045 | |
| United States, Kansas | |
| University of Kansas Cancer Center | |
| Kansas City, Kansas, United States, 66160 | |
| United States, Massachusetts | |
| Massachusetts General Hospital | |
| Boston, Massachusetts, United States, 02114 | |
| United States, Minnesota | |
| The Masonic Cancer Center University of Minnesota | |
| Minneapolis, Minnesota, United States, 55455 | |
| United States, Nebraska | |
| University of Nebraska Medical Center | |
| Omaha, Nebraska, United States, 68198-6840 | |
| United States, Oklahoma | |
| OU Health Stephenson Cancer Center | |
| Oklahoma City, Oklahoma, United States, 73104 | |
| United States, Oregon | |
| Providence Cancer Institute | |
| Portland, Oregon, United States, 97213 | |
| United States, Tennessee | |
| Vanderbilt University Medical Center | |
| Nashville, Tennessee, United States, 37212 | |
| Canada, Ontario | |
| Princess Margaret Cancer Centre | |
| Toronto, Ontario, Canada, M5G 2C1 | |
| Germany | |
| University Hospital Cologne, Clinic I for Internal Medicine | |
| Cologne, Germany, 50937 | |
Sponsors and Collaborators
SQZ Biotechnologies
| Responsible Party: | SQZ Biotechnologies |
| ClinicalTrials.gov Identifier: | NCT04084951 |
| Other Study ID Numbers: |
SQZ-PBMC-HPV-101 |
| First Posted: | September 10, 2019 Key Record Dates |
| Last Update Posted: | April 14, 2023 |
| Last Verified: | April 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by SQZ Biotechnologies:
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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 |
Additional relevant MeSH terms:
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Neoplasms Nivolumab Ipilimumab Atezolizumab |
Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |