What is the mechanism of action of this treatment?

Common treatments for solid tumors, particularly those involving therapeutic vaccines and cell-based therapies like SQZ-AAC-HPV, work by stimulating the body's immune system to recognize and attack cancer cells. Therapeutic vaccines introduce specific antigens, such as HPV16, to prompt an immune response against tumor cells expressing these antigens. Cell-based therapies involve modifying a patient's own immune cells to enhance their ability to target and destroy cancer cells. These approaches are significant for solid tumor patients as they offer a targeted treatment option that can potentially reduce tumor growth and spread while minimizing damage to healthy tissues.

What side effects are associated with this type of intervention?

Common side effects of therapeutic vaccines and cell-based therapies targeting HPV16+ cancer cells include flu-like symptoms (fever, chills, fatigue), injection site reactions (redness, swelling, pain), and gastrointestinal issues (nausea, vomiting, diarrhea). More severe but less common side effects may involve immune-related adverse events, such as inflammation of organs (e.g., colitis, hepatitis, pneumonitis) due to an overactive immune response.

What prior FDA approvals exist?

The FDA has approved several immunotherapies and checkpoint inhibitors for the treatment of solid tumors. Pembrolizumab, an immune checkpoint inhibitor targeting PD-1, has been approved for various solid tumors, including advanced melanoma, non-small cell lung cancer, and head and neck squamous cell carcinoma. Avelumab, another checkpoint inhibitor targeting PD-L1, has been approved for metastatic Merkel cell carcinoma. These treatments enhance the body's immune response against cancer cells, similar to the investigational SQZ-AAC-HPV, which is a cell-based therapy targeting HPV16+ cancer cells. While specific therapeutic vaccines targeting HPV16+ solid tumors are still under investigation, these approved immunotherapies represent significant advancements in the treatment of solid tumors.

What other types of research exist?

Promising alternatives to SQZ-AAC-HPV for HPV16+ solid tumors include: 1) Pembrolizumab, an anti-PD-1 therapy, which has shown efficacy in various HPV-associated cancers. 2) Nivolumab, another anti-PD-1 therapy, often used in combination with other agents for enhanced effect. 3) Tisotumab vedotin, an antibody-drug conjugate, which has demonstrated efficacy in recurrent or metastatic cervical cancer. These therapies are notable for their potential to improve outcomes in patients with HPV16+ solid tumors.

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Checkpoint Inhibitor

SQZ-AAC-HPV for Solid Tumors

Phase 1

Waitlist Available

Research Sponsored by SQZ Biotechnologies

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1

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)

Must not have

Has known active central nervous system metastases

History of interstitial lung disease requiring steroids

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 1 year after lpfv (last patient, first visit)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new therapy called SQZ-AAC-HPV, alone and with other immune-boosting drugs, in patients with advanced cancers caused by HPV16. The goal is to enhance the immune system's ability to fight these cancers. ADXS11-001 is a similar immunotherapy currently being tested for HPV-positive cancers.

Who is the study for?

This trial is for adults with HPV16+ solid tumors that have returned or spread, and who are HLA-A*02+. They should be relatively healthy (ECOG 0-1), have at least one measurable tumor lesion, and acceptable organ function. Participants must have tried standard treatments without success or cannot tolerate them. Those with autoimmune diseases, recent immunosuppressive treatments, unresolved severe side effects from past cancer therapies, or active infections like hepatitis B/C are excluded.

What is being tested?

The study tests SQZ-AAC-HPV alone and combined with immune checkpoint inhibitors Ipilimumab and Nivolumab in patients with various cancers including anal, cervical, head/neck cancers. It's a Phase 1 trial to assess safety, immune response enhancement capabilities of the treatment(s), their effectiveness against the tumors, and how they affect the body.

What are the potential side effects?

Potential side effects may include typical reactions to immunotherapies such as fatigue, skin reactions (rash), digestive issues (diarrhea), hormonal imbalances (thyroid disorders) due to Ipilimumab/Nivolumab; specific side effects related to SQZ-AAC-HPV will also be monitored given its investigational nature.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am 18 or older and have HLA-A*02 positive status.

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My cancer is incurable or has spread, and tests show it's HPV16+.

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I agree to have two biopsies for my condition with acceptable risk.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have cancer that has spread to my brain.

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I have a lung condition treated with steroids.

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I haven't taken high-dose steroids or immunosuppressants in the last 14 days.

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I have not had major surgery within 2 weeks before giving blood for a personalized treatment.

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I do not have active hepatitis B, hepatitis C, or tuberculosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 1 year after lpfv

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 1 year after lpfv

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 1 year after lpfv for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of participants with DLT

Number of participants with dose-limiting toxicity (DLT)

Number of participants with treatment-emergent adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0

Secondary study objectives

Amount of investigational product (IP) from individual patient blood collection - batch yield

Amount of investigational product (IP) from individual patient blood collection - product failures

Best overall Response (BoR)

+5 more

Other study objectives

Changes in T cell infiltration in the tumor micro-environment as assessed by paired biopsy

Changes in cytokine levels compared with baseline

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Part 2 Combination Safety PhaseExperimental Treatment3 Interventions

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

Group II: Part 1 Monotherapy Dose Escalation PhaseExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ipilimumab

2015

Completed Phase 3

~3070

Nivolumab

2015

Completed Phase 3

~4010

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for solid tumors, particularly those involving therapeutic vaccines and cell-based therapies like SQZ-AAC-HPV, work by stimulating the body's immune system to recognize and attack cancer cells. Therapeutic vaccines introduce specific antigens, such as HPV16, to prompt an immune response against tumor cells expressing these antigens. Cell-based therapies involve modifying a patient's own immune cells to enhance their ability to target and destroy cancer cells. These approaches are significant for solid tumor patients as they offer a targeted treatment option that can potentially reduce tumor growth and spread while minimizing damage to healthy tissues.

Emerging and mechanism-based therapies for recurrent or metastatic Merkel cell carcinoma.