Description:
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.
Title
- Brief Title: Study of SQZ-PBMC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors
- 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
Clinical Trial IDs
- ORG STUDY ID:
SQZ-PBMC-HPV-101
- NCT ID:
NCT04084951
Conditions
Interventions
Drug | Synonyms | Arms |
---|
SQZ-PBMC-HPV | | Part 1 Monotherapy Dose Escalation Phase |
Atezolizumab | | Part 2 Combination Safety Phase |
Ipilimumab | | Part 2 Combination Safety Phase |
Nivolumab | | Part 2 Combination Safety Phase |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Part 1 Monotherapy Dose Escalation Phase | Experimental | In Part 1, SQZ-PBMC-HPV as a monotherapy is administered every 3 weeks for up to a year. There are at least 3 groups ("Cohorts") in this Phase as follows:
Cohort 1: low dose SQZ-PBMC-HPV
Cohort 2: high dose SQZ-PBMC-HPV
Cohort 3: high dose SQZ-PBMC-HPV double-priming | |
Part 2 Combination Safety Phase | Experimental | 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:
Cohort 4: SQZ-PBMC-HPV RP2D (Recommended Phase 2 Dose) plus atezolizumab
Cohort 5: SQZ-PBMC-HPV RP2D plus ipilimumab
Cohort 6: SQZ-PBMC-HPV RP2D plus nivolumab
Cohort 7: SQZ-PBMC-HPV RP2D plus nivolumab and ipilimumab | - SQZ-PBMC-HPV
- Atezolizumab
- Ipilimumab
- Nivolumab
|
Part 3 Monotherapy Dose Expansion Phase | Experimental | 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:
Cohort 8: SQZ-PBMC-HPV RP2D in HPV16+ head and neck cancer patients
Cohort 9: SQZ-PBMC-HPV RP2D in HPV16+ cervical cancer patients
Cohort 10: SQZ-PBMC-HPV RP2D in HPV16+ anal cancer patients
Cohort 11: SQZ-PBMC-HPV RP2D in other HPV16+ cancer patients | |
Eligibility Criteria
Key Inclusion Criteria:
- Male or female patients ≥18 years of age who are HLA-A*02+
- Histologically confirmed incurable or metastatic solid tumors that are HPV16+
- 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 Grade 2 alopecia
- Known active hepatitis B or hepatitis C, or active mycobacterium tuberculosis
infection
- History of any Grade 4 immune-related AE (irAE) from prior immunotherapy
- Has known active central nervous system metastases
- History of interstitial lung disease requiring steroids
- Significant acute or chronic illness
- Major surgery within 2 weeks of leukapheresis
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0 |
Time Frame: | Up to 1 year after LPFV (Last Patient, First Visit) |
Safety Issue: | |
Description: | For SQZ-PBMC-HPV as a single agent and in combination with immune checkpoint inhibitors |
Secondary Outcome Measures
Measure: | Antitumor activity (Parts 1 and 2) |
Time Frame: | Up to 1 year after LPFV |
Safety Issue: | |
Description: | Tumor assessments using RECIST 1.1 of SQZ PBMC-HPV monotherapy and in combination with immune checkpoint inhibitors |
Measure: | Manufacturing feasibility (Part 1 only) |
Time Frame: | Up to 3 months after LPFV |
Safety Issue: | |
Description: | Individual patient batch yields |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | SQZ Biotechnologies |
Trial Keywords
- Solid tumors 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
Last Updated
July 23, 2021