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

Sponsor
SQZ Biotechnologies (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04892043
Collaborator
(none)
72
6
2
31.9
12
0.4

Study Details

Study Description

Brief Summary

This is a Phase 1 open-label, multicenter study of the safety and tolerability, immunogenic effects, antitumor activity, and pharmacodynamics of SQZ-AAC-HPV as monotherapy and in combination with 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
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
72 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Multicenter, Open-Label Study of SQZ-AAC-HPV as Monotherapy and in Combination With Immune Checkpoint Inhibitors in HLA-A*02+ Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors
Actual Study Start Date :
Aug 19, 2021
Anticipated Primary Completion Date :
Apr 15, 2024
Anticipated Study Completion Date :
Apr 15, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1 Monotherapy Dose Escalation Phase

In Part 1, SQZ-AAC-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 1a: low dose SQZ-AAC-HPV Cohort 1b: high dose SQZ-AAC-HPV Cohort 1c: higher or lower dose SQZ-AAC-HPV

Biological: SQZ-AAC-HPV
Activating antigen carriers (AACs) cell therapy; therapeutic vaccine engineered from red blood cells manufactured with immunogenic epitopes of HPV16

Experimental: Part 2 Combination Safety Phase

In Part 2, SQZ-AAC-HPV in combination with immune checkpoint inhibitors (1) ipilimumab, (2) nivolumab, or (3) nivolumab plus ipilimumab is administered every 3 weeks up to a year, but the immune checkpoint inhibitors may be administered up to 2 years. There are 3 groups ("Cohorts") in this Phase as follows: Cohort 2a: SQZ-AAC-HPV RP2D (Recommended Phase 2 Dose) plus ipilimumab Cohort 2b: SQZ-AAC-HPV RP2D plus nivolumab Cohort 2c: SQZ-AAC-HPV RP2D plus nivolumab and ipilimumab

Biological: SQZ-AAC-HPV
Activating antigen carriers (AACs) cell therapy; therapeutic vaccine engineered from red blood cells manufactured with immunogenic epitopes of HPV16

Drug: Ipilimumab
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody

Drug: Nivolumab
Programmed cell death 1 (PD-1) blocking antibody

Outcome Measures

Primary Outcome Measures

  1. Number of participants with treatment-emergent adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0 [Up to 1 year after LPFV (Last Patient, First Visit)]

    For SQZ-AAC-HPV administered as monotherapy, and in combination with immune checkpoint inhibitors (Part 1 and Part 2, respectively)

  2. Number of participants with dose-limiting toxicity (DLT) [Through Day 28]

    For SQZ-AAC-HPV as a monotherapy (Part 1)

  3. Number of participants with DLT [Through Day 28]

    For SQC-AAC-HPV in combination with immune checkpoint inhibitors (Part 2)

Secondary Outcome Measures

  1. Progression-free survival (PFS) [Through start of a new anticancer therapy, up to 2 years after the 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-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  2. Overall survival (OS) [Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product]

    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-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  3. 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-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  4. Duration of Response (DoR) [Through start of a new anticancer therapy, up to 2 years after the 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-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  5. 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-AAC-HPV as a monotherapy, in combination with immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  6. Disease-control rate (DCR) [Through start of a new anticancer therapy, up to 2 years after the 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-AAC-HPV as a monotherapy, in combination immune checkpoint inhibitors (Part 1, and Part 2, respectively).

  7. 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) (Part 1)

  8. 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 (Part 1)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 blood collection for manufacture of autologous blood product 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 of blood collection for manufacture of autologous blood product

Exclusion Criteria:
  • Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to blood collection for manufacture of autologous blood product. For prior therapies with a half-life longer than 3 days, discontinuation of the therapy must have occurred at least 28 days prior to Cycle 1 Day 1

  • Systemic treatment with either corticosteroids (>10 mg of prednisone or the equivalent per day) or other immunosuppressive medications within 14 days prior to Cycle 1 Day 1

  • 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 blood collection for manufacture of autologous blood product, 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 blood collection for manufacture of autologous blood product

Contacts and Locations

Locations

Site City State Country Postal Code
1 City of Hope Medical Center Duarte California United States 91010
2 UC San Diego Moores Cancer Center La Jolla California United States 92093
3 Barbara Ann Karmanos Cancer Institute Detroit Michigan United States 48201
4 Roswell Park Comprehensive Cancer Center Buffalo New York United States 14263
5 Oregon Health & Science University Portland Oregon United States 97239
6 Clínica Universidad de Navarra Pamplona Spain 31008

Sponsors and Collaborators

  • SQZ Biotechnologies

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
SQZ Biotechnologies
ClinicalTrials.gov Identifier:
NCT04892043
Other Study ID Numbers:
  • SQZ-AAC-HPV-101
First Posted:
May 19, 2021
Last Update Posted:
Aug 15, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by SQZ Biotechnologies
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 15, 2022