Phase 2 INSPIRE Trial of IRX-2 Misses EFS End Point in Head and Neck Cancer

The phase 2 INSPIRE trial (NCT02609386) evaluating IRX-2 in patients with newly diagnosed stage II, III, or IVA squamous cell carcinoma of the oral cavity failed to meet its primary end point of event-free survival (EFS), according to Brooklyn ImmunoTherapeutics.¹

However, the study met its key objective of identifying patient populations that may benefit from the agent in the neoadjuvant setting. Data showed that at 2 years of follow-up in the intention-to-treat population, which consisted of 105 patients, the median EFS was 48.3 months. In the control arm, median EFS was not reached (HR 1.10; 95% CI, 0.6-2.1; P=0.62).

IRX-2 is a multi-cytokine biologic immunotherapy currently in development for treatment in multiple solid tumor indications. The primary cell-derived immunotherapy is administered locally by subcutaneous injection and aims to activate T cells and to generate an anti-tumor response.

“IRX-2 immunotherapy treatment was administered as a local subcutaneous injection and was well tolerated in this patient population with squamous cell head and neck cancer of the oral cavity in the neoadjuvant setting,” said Roger Sidhu, MD, chief medical officer of Brooklyn ImmunoTherapeutics, INC, in the press release. “We observed compelling trends in favor of IRX-2 in patients with higher stage disease and those that did not receive chemotherapy as part of adjuvant treatment, representing patient populations with high unmet need and who comprise a significant proportion of patients with head and neck cancer. The mechanism of action of IRX-2 and prior preclinical and translational studies of IRX-2 suggest potential synergy with checkpoint inhibitors and represents a novel combination immunotherapy strategy to explore in patients that may not be eligible for or require intensive adjuvant treatment.”

In the open-label, phase 2 INSPIRE study, patients are randomized in a 2:1 ratio to receive either IRX-2 or control in order to compare IRX-2 to the standard-of-care in patients with newly diagnosed stage II, III, or IVA squamous cell carcinoma of the oral cavity.²

A total of 150 patients enrolled in the study with 105 in the intention-to-treat population. Patients in the experimental arm received the IRX regimen with IRX-2, cyclophosphamide, indomethacin, zinc-containing multivitamin, and omeprazole as neoadjuvant and adjuvant therapy while those in the active comparator arm received the same regimen without IRX-2.

Enrollment in the study was open to patients aged 18 years and older with pathologically confirmed clinical stage II, III, or IVA squamous cell cancer of the oral cavity, which excluded disease in the lip.

Other eligibility criteria consisted of having disease that was surgically resectable with curative intent, hematological function, hepatic function, prothrombin time and partial thromboplastin time < 1.4x the ULN, calculated creatinine clearance > 50 mL/minute, a negative urine/serum pregnancy test, and a Karnofsky performance status of 70% or greater. For females of childbearing potential, one must use a highly effective form of pregnancy prevention from the time of screening, during the study, and 30 days after the last dose of study regimen while males must use condoms with spermicide for the same amount of time.

The primary end point of the trial was to estimate EFS at 2 years with key secondary end points including overall survival (OS), and safety of IRX-2.

Key pre-specified subgroups were defined by stage and type of adjuvant treatment, findings revealed that outcomes favored the regimen which included IRX-2. In these subgroups, patients were less likely to experience an EFS event in the IRX-2 arm compared to control.

The trends in EFS rates showed that at 2 years of follow-up in patients with stage III and IV disease favored IRX-2 with rates of 57.2 (40.3-70.9) vs 49.4 (28.3- 67.4). Patients that did not receive chemotherapy as part of their adjuvant treatment demonstrated an EFS estimate at 2 years of follow-up of 76.4 (52.2-89.4) vs 60.6 (29.4-81.4), also in favor of IRX-2.

In regard to safety, no new safety signals were identified with IRX-2. Adverse events (AE) related that were found to be related to the study treatment were higher in the IRX-2 arm than the control arm (55.9% vs 40%). These AEs were primarily caused by injection site reactions and fatigue.

These results of the INSPIRE study are expected to be presented at a scientific conference later in 2022.

“The INSPIRE study achieved its primary objective of identifying patient populations that may benefit from IRX-2 in the neoadjuvant setting,” said Matt Angel, PhD, chief executive officer of Brooklyn ImmunoTherapeutics, Inc, in the press release. “These encouraging results are a testament to the design of the INSPIRE study and provide a clear path forward for testing in patient populations that may benefit from treatment with IRX-2 in combination with checkpoint inhibitors. The potential to offer an effective, well-tolerated treatment to patients with advanced head and neck cancer who are ineligible for chemotherapy is particularly exciting.”

References:

1. Brooklyn immunotherapeutics announces results of phase 2 study of IRX-2 in head and neck cancer. News release. Brooklyn ImmunoTherapeutics, Inc. July 26, 2022. Accessed July 27, 2022. https://bit.ly/3JaMPHV

2. IRX-2 regimen in patients with newly diagnosed stage II, III, or IVA squamous cell carcinoma of the oral cavity (INSPIRE). ClinicalTrials.gov. Updated August 12, 2022. Accessed July 27, 2022. https://clinicaltrials.gov/ct2/show/NCT02609386