IRX-2 Regimen + Durvalumab for Squamous Cell Carcinoma

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining two treatments, IRX-2 and Durvalumab (an immunotherapy drug), can safely enhance the immune response in tumors of individuals with squamous cell carcinoma, a cancer affecting areas like the mouth and throat. The trial targets those whose cancer has returned or spread and cannot be cured with surgery or radiation. Suitable candidates have been diagnosed with this specific cancer type and are experiencing a recurrence or metastasis. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that the IRX-2 treatment was well-tolerated by patients with head and neck squamous cell carcinoma (HNSCC) who did not respond to surgery or radiation. Most patients handled the treatment without severe side effects. Another study supported these findings, showing that the IRX-2 treatment was safe for patients with untreated squamous cell cancer.

The FDA has already approved durvalumab for treating other cancers, such as bladder cancer and non-small cell lung cancer. In these cases, patients have generally tolerated it well. Some may experience side effects, but they are usually manageable.

Both IRX-2 and durvalumab have shown promising safety results in previous research, suggesting they could be safe for use in this new trial for squamous cell carcinoma. However, since this is a phase 1 trial, the main goal is to ensure the treatment is safe for humans, so researchers will closely monitor participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the IRX-2 regimen combined with Durvalumab for squamous cell carcinoma because it introduces a novel approach to immunotherapy. Unlike standard treatments like chemotherapy or radiation, IRX-2 is a cytokine-based therapy that boosts the immune system's response to cancer cells. Durvalumab, an immune checkpoint inhibitor, works by blocking the PD-L1 protein, allowing T-cells to attack cancer more effectively. This combination aims to enhance the body's natural defenses against cancer, potentially offering a more targeted and effective treatment than traditional methods.

What evidence suggests that the IRX-2 regimen and Durvalumab could be effective for squamous cell carcinoma?

Research has shown that the IRX-2 treatment, studied in this trial, can enhance the immune system in cancer patients, but past studies have not clearly demonstrated longer survival. Some patients experienced changes in their tumors and immune system, but these did not result in extended survival. In contrast, durvalumab, another treatment option in this trial, has shown promise in treating various cancers, including head and neck cancer. Previous studies have indicated that durvalumab led to lasting reductions in tumor size for some patients. Overall, while IRX-2 may boost the immune system, durvalumab has more consistently reduced tumor size in similar cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Christine Chung, M.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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, 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01693562

NCT01693562 | A Phase 1/2 Study to Evaluate MEDI4736 Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort. Eur J Cancer. 2019 Mar ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0959804919300073

Safety and efficacy of durvalumab in patients with head ... Durvalumab monotherapy was safe in previously treated recurrent/metastatic head and neck squamous cell carcinoma. Durable antitumour responses were observed.

4. researchgate.net researchgate.net/publication/313341968_Updated_safety_and_efficacy_of_durvalumab_MEDI4736_an_anti-PD-L_1_antibody_in_patients_from_a_squamous_cell_carcinoma_of_the_head_and_neck_SCCHN_expansion_cohort

Updated safety and efficacy of durvalumab (MEDI4736), an ... In a phase 1/2 study to evaluate durvalumab, 11 an ORR of 11% was achieved with durvalumab monotherapy; in the Phase II Study of Durvalumab ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10342070/

A Phase Ib Study of Durvalumab (MEDI4736) in ... Even in patients with tumor diameters > 6 cm, we have shown a five-year LC rate of 70% for cervical squamous cell carcinoma [13]. Wakatsuki et al. reported a ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20539208/

A phase 1 safety study of an IRX-2 regimen in patients with ... Conclusions: The IRX-2 regimen was tolerated in patients with advanced HNSCC who failed surgery and/or radiation therapy. The safety and antitumor activity ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00210470

A Phase 2 Clinical Trial of the Safety and Effects of IRX-2 in ... This was a Phase 2a trial to investigate the safety and biological activity of the RIX-2 Regimen in patients with untreated, resectable squamous cell cancer of ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2772906024005521

Neoadjuvant cytokine (IRX-2) immunotherapy for ... The safety and preliminary efficacy of this neoadjuvant IRX-2 regimen in patients with HNSCC has been documented in small Phase I and Phase II clinical trials ...

9. patlynk.com patlynk.com/trial/NCT00210470

A Phase 2 Clinical Trial of the Safety and Effects of IRX ... This was a Phase 2a trial to investigate the safety and biological activity of the RIX-2 Regimen in patients with untreated, resectable squamous cell cancer ...

10. targetedonc.com targetedonc.com/view/phase-2-inspire-trial-of-irx-2-misses-efs-end-point-in-head-and-neck-cancer

Phase 2 INSPIRE Trial of IRX-2 Misses EFS End Point in ... IRX-2 did not demonstrate a statistically significant improvement in event-free survival as neoadjuvant therapy vs standard of care in patients ...