IRX-2 Immunotherapy Misses EFS End Point in Newly Diagnosed Head and Neck Cancer

Roger Sidhu, MD

The multi-cytokine biologic immunotherapy IRX-2 (citoplurikin) failed to demonstrate a statistically significant improvement in event-free survival (EFS) as neoadjuvant therapy compared with standard of care in patients with newly diagnosed, stage II, III, or IVA squamous cell carcinoma of the oral cavity, missing the primary end point of the phase 2 INSPIRE trial (NCT02609386).^1,2

Topline findings from the trial showed that at 2 years of follow-up in the intention-to-treat population (n = 105), the median EFS was 48.3 months with IRX-2 and was not reached in the control arm (HR, 1.10; 95% CI, 0.6-2.1; P = .62).

The full results from the study will be presented at an upcoming medical meeting.

“We thank the patients and their families for their participation in this trial,” Roger Sidhu, MD, chief medical officer of Brooklyn ImmunoTherapeutics, stated in a press release. “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.”

IRX-2 is a primary cell-derived multi-cytokine biologic immunotherapy in development across solid tumors. The agent is designed to activate T cells to produce antitumor activity and is administered by subcutaneous injection

“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 represent a novel combination immunotherapy strategy to explore in patients that may not be eligible for or require intensive adjuvant treatment,” Sidhu added.

INSPIRE was an open-label, randomized phase 2 trial that enrolled patients with newly diagnosed, untreated, surgically resectable squamous cell cancer of the oral cavity.

Patients were randomized 2:1 to IRX-2 plus cyclophosphamide, indomethacin, zinc, omeprazole, or cyclophosphamide, indomethacin, zinc, and omeprazole.

The primary end point of the study was the estimated 2-year EFS rate, with key secondary end points of overall survival and safety.

Additional results demonstrated favorable outcomes with IRX-2 across prespecified subgroups defined by stage and type of adjuvant treatment. Patients in these subgroups were less likely to experience an EFS event in the IRX-2 arm vs control.

The estimated 2-year EFS rate in patients with stage III and IV disease favored the use of IRX-2 at 57.2% (95% CI, 40.3%-70.9%) vs 49.4% (95% CI, 28.3%-67.4%) with control. In patients that received radiation only in the adjuvant setting, the estimated 2-year EFS rates were 76.4% (95% CI, 52.2%-89.4%) and 60.6% (95% CI, 29.4%-81.4%), respectively.

Additionally, no new safety signals occurred with IRX-2, although treatment-related adverse effects were higher in the investigational arm compared with the control arm, at 55.9% and 40%, respectively, and were driven largely by injection-site reactions and fatigue.

“The INSPIRE study achieved its primary objective of identifying patient populations that may benefit from IRX-2 in the neoadjuvant setting,” Matt Angel, PhD, chief executive officer of Brooklyn ImmunoTherapeutics, said.

“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,” Angel concluded.

References

1. Brooklyn ImmunoTherapeutics announces results of phase 2 study of IRX-2 in head and neck cancer. News release. Brooklyn ImmunoTherapeutics. July 26, 2022. Accessed July 27, 2022. https://yhoo.it/3BiggFW
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