First-Line Keytruda Combo Elicits OS Results in Head and Neck Cancers

Keytruda plus Efti led to 17.6-month overall survival in patients with head and neck squamous cell carcinoma and a PD-L1 score less than one.

First-line treatment of Keytruda (pembrolizumab) plus eftilagimod alfa (Efti) elicited an overall survival (OS) of 17.6 months in patients with recurrent/metastatic head and neck squamous cell carcinoma and a PD-L1 expression below one (combined positive score [CPS] less than 1).

These data were derived from cohort B the phase 2b TACTI-003 (KEYNOTE-C34) trial, which were shared in a news release from Immutep Limited.

“We are excited to see this strong survival benefit for head and neck cancer patients with such cold tumors. Combining these two complementary immunotherapies has led to a 7-fold increase in response rates and a more than doubling of median overall survival as compared to historical results from anti-PD-1 monotherapy. Driving durable responses that translate into clinically meaningful survival holds tremendous promise for these patients in need of more tolerable and efficacious therapies,” said Marc Voigt, CEO of Immutep.

Moreover, the combination continues to be well-tolerated, with no new safety concerns observed. The safety profile and mature overall survival data support the high overall response rate, including several complete responses, seen with this combination in patients with first-line head and neck squamous cell carcinoma with a combined positive score less than one.

Treatment with the therapeutic combination was evaluated in a group of 31 patients and demonstrated favorable outcomes when compared with historical data from the two-current standard-of-care treatments for first-line head and neck squamous cell carcinoma patients with a CPS less than one. For example, treatment with Erbitux (cetuximab) plus chemotherapy elicited a 10.7-months overall survival. Moreover, other anti-PD-1 therapies in combination with chemotherapy elicited data of 11.3-months and anti-PD-1 monotherapy treatment showed an overall survival of 7.9-months.

Importantly, patients with CPS of less than one who are being treated for their head and neck squamous cell carcinoma in the first-line are a patient population with high unmet medical need. For example, anti-PD-1 therapy, when given alone (without chemotherapy), is only approved for patients who express PD-L1/have a CPS of more than one, leaving these patients without reliable treatment considerations, as all available treatment options for patients within this population include chemotherapy.

“There is a high unmet need in 1L HNSCC patients with cold tumors and PD-L1 CPS less than 1, due to the lack of an approved immunotherapy-only treatment regimen and a lack of competitor trials with chemotherapy-free approaches targeting this patient population. Given the strength of the efficacy and safety results generated to date with Efti in combination with pembrolizumab, we will meet with regulators to discuss next steps and potential paths to approval,” Voigt added.

What is Eftilagimod Alfa?

Efti, developed by Immutep, is an agonist that stimulates both innate and adaptive immunity for the treatment of cancer. The agent, after binding to major histocompatibility complex Class II molecules, then leads to the activation and increase of the number of key immune cells — such as T cells, dendritic cells, natural killer cells, and monocytes — which, in turn, work to identify and destroy cancer cells. The agent also upregulates the expression of key biological molecules, which further strengthen the immune system’s capacity to combat cancer.

This agent is under investigation for the treatment of a variety of solid tumors, according to the news release. This includes solid tumors such as non–small cell lung cancer, head and neck squamous cell carcinoma and metastatic breast cancer. Its favorable safety profile supports its use in various combination regimens, including with other immunotherapy agents, like Keytruda, or even other chemotherapy agents.

The United States Food and Drug Administration (FDA) has granted Efti fast track designation for the agents' use in first-line treatment of both head and neck squamous cell carcinoma and non–small cell lung cancer.

Furthermore, Immutep shared that they have requested a meeting with the regulatory agency to discuss next steps. According to the news release, these next steps include a potential path to approval for this therapy in the first-line treatment of patients with head and neck squamous cell carcinoma who have a PD-L1 CPS of less than one.

Finally, patient follow up, data collection, cleaning and analysis will be continuing for the TACTI-003 ahead of further updates later this year from the Company.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.