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

SQZ Biotechnologies

Status and phase: Completed; Phase 1

Conditions: Adult Solid Tumor

Treatments: Drug: Ipilimumab; Drug: Nivolumab; Drug: Atezolizumab; Biological: SQZ-PBMC-HPV

Study type: Interventional

Funder types: Industry

Identifiers

NCT04084951

SQZ-PBMC-HPV-101

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Part 1 Monotherapy Dose Escalation Phase

Experimental group

Description:

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: * Cohort 1: specified dose SQZ-PBMC-HPV * Cohort 2: specified dose SQZ-PBMC-HPV * Cohort 3: specified dose SQZ-PBMC-HPV double-priming

Treatment:

Biological: SQZ-PBMC-HPV

Part 2 Combination Safety Phase

Experimental group

Description:

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

Treatment:

Drug: Ipilimumab

Drug: Atezolizumab

Biological: SQZ-PBMC-HPV

Drug: Nivolumab

Part 3 Monotherapy Dose Expansion Phase

Experimental group

Description:

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

Treatment:

Biological: SQZ-PBMC-HPV