New Immunotherapy Combination Effective in Head and Neck Cancer

Head and neck cancer image: © CLIPAREA.com- stock.adobe.com

Eftilagimod alpha (efti), a soluble LAG-3 fusion protein, in combination with pembrolizumab (Keytruda) led to positive efficacy and disease control findings in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with negative PD-L1 expression, according to findings presented at the European Society for Medical Oncology (ESMO) Virtual Plenary on July 11, 2024.¹

An overall response rate (ORR) of 35.5% (n = 11) was observed in patients in cohort B of the TACTI-003 (KEYNOTE-PNC-34) phase 2b trial (NCT04811027), with a complete response (CR) rate of 9.7% (n = 2). A disease control rate (DCR) of 58.1% was also reported. These compared favorably to historic controls of 5.4% ORR, 0% CR rate, and 32.4% DCR with anti-PD-1 monotherapy.

“This is really significant for patients with head and neck squamous cell carcinomas who have a CPS less than one and for whom chemotherapy is the current first line treatment. Achieving complete responses in this group bodes well for this immunotherapy combination's future potential, especially given the positive trend in response durability. The clinically meaningful response rate and high unmet medical need warrant further investigation of eftilagimod plus pembrolizumab in this patient population,” said Robert Metcalf, MD, PhD, The Christie NHS Foundation Trust, in a presentation of the data.

Regarding safety, the combination appears tolerable, and no new safety signals have been identified.

Immutep, the manufacturer of efti, will present these findings to regulatory authorities. Efti previously received FDA fast track designation for the first-line treatment of HNSCC regardless of PD-L1 expression.

About the Phase 2b TACTI-003 Study

The TACTI-003 has enrolled 171 patients across centers in the US, Europe, and Australia.² Patients with a combined positive score (CPS) of 1 or lower are randomized to receive pembrolizumab at 400 mg every 6 weeks for up to 18 cycles plus efti at 30 mg every 2 weeks for the first 4 cycles, followed by every 3 weeks for up to 18 cycles or pembrolizumab alone at 400 mg every 6 weeks for up to 18 cycles. Patients with a CPS over 1 receive pembrolizumab plus efti in the same dosing schedule.

The primary end point of the study is ORR, and secondary end points include overall survival, time to and duration of responses, DCR, progression-free survival, occurrence of anti-efti-specific antibodies, adverse events, and quality of life. PD-L1 expression, circulating level of TH1 biomarker, and correlation of biomarkers with efficacy and safety end points serve as exploratory outcome measures.

Patients are eligible for enrollment if they have histologically or cytologically confirmed recurrent HNSCC that is not amenable to curative treatment and an ECOG performance status of 0 to 1. Those with active central nervous system metastases or receiving continuous treatment with immunosuppressive agents or corticosteroids are not eligible for enrollment in the study. Patients also cannot have received prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 agents.

REFERENCES:

1. Immutep reports positive results in first line head and neck squamous cell carcinoma in patients with negative PD-L1 expression. News release. Immutep. July 12, 2024. Accessed July 12, 2024. https://tinyurl.com/33ajjfen

2. Combination study with eftilagimod alpha (a soluble LAG-3 fusion protein) and pembrolizumab in patients with recurrent or metastatic HNSCC (TACTI-003). ClincalTrials.gov. Updated July 3, 2024. Accessed July 12, 2024. https://clinicaltrials.gov/study/NCT04811027