Eftilagimod Alfa/Pembrolizumab May Improve OS in HNSCC With CPS < 1

New data from the TACT-003 trial show a promising OS of 17.6 months.

The addition of eftilagimod alfa (efti) to pembrolizumab (Keytruda) showed promising overall survival (OS) outcomes as a frontline therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and a PD-L1 Combined Positive Score (CPS) lower than 1, according to an announcement from the drug’s developer, Immutep Limited.¹

The press release highlighted findings from cohort B of the phase 2b TACTI-003 trial (NCT04811027), which is evaluating the safety and efficacy of the drug combination. Mature data with a cut-off of March 31, 2025, showed a median OS of 17.6 months in the 31 evaluable patients assigned to the pembrolizumab/efti regimen.

“We are excited to see this strong survival benefit for head and neck cancer patients with such cold tumors,” said Marc Voigt, the CEO of Immutep Limited, in the release. “Combining these 2 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.”

According to the release, historical data show a 10.7-month OS with standard-of-care (SOC) cetuximab plus chemotherapy, 11.3-month OS with SOC anti-PD-1 therapy plus chemotherapy, and 7.9-month OS with SOC anti-PD-1 monotherapy. The release noted that treatment options for those with HNSCC and a CPS less than 1, who comprise 20% of patients with HNSCC, all include chemotherapy.

Additionally, data from the phase 4 KEYNOTE-B10 study (NCT04489888) showed that first-line treatment with pembrolizumab plus chemotherapy yielded promising response results in patients with HNSCC and a PD-L1 CPS less than 1. Specifically, the confirmed objective response rate (ORR) in those with a PD-L1 CPS less than 1 was 65% (95% CI, 40.8%-84.6%).²

“Driving durable responses that translate into clinically meaningful survival holds tremendous promise for these patients in need of more tolerable and efficacious therapies,” noted Voigt on the OS development.

Prior Efficacy Results

Data presented in a poster at the 2024 ESMO Immuno-Oncology Annual Congress showed that the drug combination had on ORR of 35.5% (95% CI, 19.2%-54.6%) using RECIST 1.1 and 38.7% (95% CI, 21.8%-57.8%) using iRECIST criteria.³ Responses were confirmed in 91% of cases, with a confirmed ORR by RECIST 1.1 criteria of 32.3% (95% CI, 16.7%-51.4%). Four patients had complete response.

The median time to response was 2.1 months. A median progression-free survival (PFS) of 5.8 months was observed at a median follow-up of 16.4 months. Likewise, the 6-month PFS rate was 48.4%. Patients experienced a median 9.3-month duration of response (DOR).

Associated Adverse Events

The release stated that the drug combination was well tolerated and presented no new safety signals.¹

In the findings previously presented, the most common adverse events (AEs) of any grade were fatigue (21.2%), nausea (21.2%), weight loss (18.2%), hypothyroidism (18.2%), constipation (18.2%), pyrexia (15.2%), arthralgia (15.2%), gamma-glutamyltransfterase increase (15.2%), diarrhea (15.2%), and anemia (15.2%).³

No fatal AEs or serious AEs were observed. Grade 3 or higher AEs occurred in 15.2% of patients, and AEs leading to treatment discontinuation occurred in 9.1% of patients.

Treatment was discontinued in 25 patients, due to disease progression (92.0%), AEs (3.2%), and physician decision (3.2%).

Path To Approval

The treatment previously received FDA fast track designation, and according to the release, Immutep has requested a meeting with the FDA in order to determine possible steps toward approval for the combination. Patient follow-up, data collection, cleaning, and analysis are not yet complete in the TACTI-003 trial. Further updates are expected within the year.

“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,” said Voigt in the news release. “There is a high unmet need in [firstline] 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.”

References

1. Immutep’s efti in combination with Keytruda® (pembrolizumab) drives strong overall survival in head and neck cancer with CPS <1. Immutep Limited. May 5, 2025. Accessed May 5, 2025. https://www.globenewswire.com/news-release/2025/05/05/3074011/0/en/Immutep-s-Efti-in-Combination-with-KEYTRUDA-pembrolizumab-Drives-Strong-Overall-Survival-in-Head-and-Neck-Cancer-with-CPS-1.html
2. Dzienis M, Cundom J, Fuentes CS, et al. Pembrolizumab plus carboplatin and paclitaxel as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (KEYNOTE-B10): a single-arm phase IV trial. J Clin Oncol. Published online July 22, 2024. doi:10.1200/JCO.23.02625
3. Forster M, Laban S, Metcald R, et al. TACTI-003 cohort B: eftilagimod alpha (soluble LAG-3) and pembrolizumab in first-line recurrent or metastatic head & neck squamous cell carcinoma with CPS <1. Presented at: ESMO Immuno-Oncology Annual Congress; December 11-13, 2024; Geneva, Switzerland. Abstract 620.