IRX-2 Regimen + Durvalumab for Squamous Cell Carcinoma

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Autoimmune disorders, Active infection, Cardiopulmonary disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

19 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use immunosuppressive medications within 14 days before starting the trial, and certain anticoagulants or platelet inhibitors must be safely stopped. It's best to discuss your specific medications with the study team.

Is the combination of IRX-2 Regimen and Durvalumab safe for humans?

Durvalumab, also known as Imfinzi, has been shown to have a manageable safety profile in treating various cancers, but it can cause side effects like lung issues, which sometimes lead to stopping the treatment. It's important to weigh these risks when considering participation in a clinical trial. ^{1 2 3 4 5}

What makes the IRX-2 Regimen + Durvalumab treatment unique for squamous cell carcinoma?

The IRX-2 Regimen combined with Durvalumab is unique because it involves a novel combination of an immune-boosting regimen (IRX-2) with Durvalumab, a monoclonal antibody that enhances the immune system's ability to fight cancer by blocking a protein called PD-L1. This combination aims to improve the body's immune response against squamous cell carcinoma, potentially offering a new treatment option where standard therapies may be limited. ^{1 3 6 7 8}

What is the purpose of this trial?

This trial is testing a combination of treatments that boost the immune system and help it attack cancer cells. It targets patients with specific types of head and neck cancers that cannot be cured with standard treatments. The goal is to see if these treatments are safe and effective in improving the body's ability to fight cancer.

Research Team

Christine Chung, M.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria

Adults with squamous cell carcinoma in areas like the mouth, throat, or larynx that can't be cured by surgery or radiation. They must have a tumor that can be measured and biopsied, weigh over 30 Kg, and have an ECOG score of 0-2 indicating they are relatively active. Women must not be pregnant and all participants should agree to use birth control.

Inclusion Criteria

Participants must be willing and able to give informed consent and adhere to protocol therapy

Participants must have measurable disease as per RECIST version 1.1

My cancer is confirmed as squamous cell carcinoma in the specified areas.

Exclusion Criteria

I have no medical conditions or past treatments that would prevent me from receiving certain cancer therapies.

Known infection with specific viruses

Allergy to specific medications

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 - Dose Escalation

Participants receive IRX-2 regimen and durvalumab with dose escalation based on safety profile

6 weeks

Weekly visits for dose escalation monitoring

Phase 2 - Dose Expansion

Participants receive the recommended dose level from the dose finding phase

Up to 12 months

Regular visits for tumor sample collection and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months post treatment

Treatment Details

Interventions

• Durvalumab
• IRX-2 Regimen

Trial Overview The trial is testing if combining the IRX-2 regimen with Durvalumab improves immune response within tumors compared to before treatment. The safety profile of this combination will also be assessed for people with incurable head and neck squamous cell carcinoma.

Participant Groups

Group I: Phase 2 - Dose Expansion Experimental Treatment 2 Interventions

14 patients will be enrolled at the recommended dose level from the dose finding phase for a total enrollment of 20 patients; however, investigators will replace patients with any missing tumor sample collection and continue enrollment until there are at least 20 pre- and post-treatment paired tumors (i.e. minimum 2 of 3 tumors per patient). The 6 patients treated at the recommended dose in the dose finding phase of the study will be counted as a part of the dose expansion patient population,

Group II: Phase 1 - Dose Escalation Experimental Treatment 2 Interventions

Six patients will be enrolled at Dose Level 1 with IRX-2 230 units/day in combination with cyclophosphamide and durvalumab and treated sequentially at least 1 week apart. If less than 2 out of 6 patients have DLTs in Dose Level 1, the dose will be escalated to administration of IRX-2 460 Units/day in combination with cyclophosphamide and durvalumab as Dose Level 2. If 2 of 6 patients have DLTs, stop accrual and re-evaluate. In the next safety phase, six patients at IRX-2 460 Units/day in combination with cyclophosphamide and durvalumab will be enrolled and treated sequentially (at least 1 week apart). If DLT occurs in less than 2 of 6 patients during the first 6 weeks of treatment, enrollment can continue in the dose expansion phase at Dose Level 2. If DLT is observed in 2 of 6 patients, accrual will be stopped and Dose Level 1 will resume in the dose expansion phase.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Brooklyn ImmunoTherapeutics, LLC

Industry Sponsor

Trials

8

Recruited

5,500+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

Evaluation of Durvalumab-induced Lung Toxicity Using a Spontaneous Reporting Database. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Comparison of 2-Weekly Versus 4-Weekly Durvalumab Consolidation for Locally Advanced NSCLC Treated With Chemoradiotherapy: A Brief Report. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Durvalumab Treatment Patterns for Patients with Unresectable Stage III Non-Small Cell Lung Cancer in the Veterans Health Administration (VHA): A Nationwide, Real-World Study. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable, locally advanced NSCLC patients. [2022]