Study launches of eftilagimod alpha plus avelumab in urothelial cancer

The first patient has been treated in the phase 1 INSIGHT-005 trial, which is evaluating the efficacy and safety of the combination of the investigational agent eftilagimod alpha and the PD-L1 inhibitor avelumab (Bavencio) in patients with metastatic urothelial cancer.¹

The study is being conducted by investigators at the Institute of Clinical Cancer Research IKF at Krankenhaus Nordwest in Frankfurt and other German cancer centers.

According to Immutep, the developer of the treatment, eftilagimod alpha is a “soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer.”¹

The open-label INSIGHT-005 trial has an enrollment goal of up to 30 patients. The study is being conducted by investigators at the Institute of Clinical Cancer Research IKF at Krankenhaus Nordwest in Frankfurt and other German cancer centers.

“Immunotherapy has made great strides in improving clinical outcomes for patients with bladder cancer, including avelumab that has set a new standard of care for many metastatic urothelial carcinoma patients, and we are pleased to commence patient enrollment in the INSIGHT-005 study that we hope will build upon this progress. The chemotherapy-free IO combination utilizing eftilagimod alpha and avelumab has already generated encouraging efficacy and safety in difficult-to-treat advanced solid tumors, and this trial will help further elucidate how eftilagimod alpha’s unique immune system activation may complement and enhance the ability of immune checkpoint inhibitors like avelumab to fight cancer,” Immutep CSO, Frédéric Triebel, MD, PhD, stated in a press release.¹

Previously released data from the phase 1 INSIGHT-004 study showed promising efficacy signals and a manageable safety profile for the combination in patients with advanced solid tumors.² In the small study population of 12 patients, the combination induced a response or stable disease in half of the patients. Of note, the investigators reported responses in patients with low and negative tumor expression levels of PD-L1.

The INSIGHT-005 trial is an investigator-initiated study that is being jointly funded by Immutep and Merck KGaA, Darmstadt.

Eftilagimod alpha was previously granted FDA Fast Track Designations for use in combination with pembrolizumab (Keytruda) for the treatment of patients with non–small cell lung cancer and the treatment of patients with head and neck squamous cell carcinoma.³

Avelumab has multiple FDA-approved indications for urothelial carcinoma.⁴ The PD-L1 inhibitor is approved for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Avelumab is also approved as a maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.

References

1. First Patient Dosed in Trial Evaluating Efti and the Anti-PD-L1 Therapy BAVENCIO® in Metastatic Urothelial Cancer. Published online January 4, 2023. Accessed January 5, 2023. https://www.immutep.com/detail/first-patient-dosed-in-trial-evaluating-efti-and-the-anti-pd-l1-therapy-bavencio-r-in-metastatic-urothelial-cancer.html

2. Goetze TO, Daniel MW, Rafiyan M-R, et al. Advanced safety and efficacy data from stratum D of the phase I INSIGHT platform trial evaluating feasibility and safety of eftilagimod alpha combined with avelumab in advanced solid tumors. Presented at: 2021 Congress of the European Society for Medical Oncology. September 16 – September 21, 2021. Lugano, Switzerland. doi.org/10.1016/j.annonc.2021.08.1369

3. Immutep Receives FDA Fast Track Designation for LAG-3 Therapeutic Eftilagimod Alpha for First Line Non-Small Cell Lung Cancer. Published online October 4, 2022. Accessed January 5, 2023. https://www.globenewswire.com/news-release/2022/10/04/2527727/0/en/Immutep-Receives-FDA-Fast-Track-Designation-for-LAG-3-Therapeutic-Eftilagimod-Alpha-for-First-Line-Non-Small-Cell-Lung-Cancer.html

4. BAVENCIO® (avelumab) injection, for intravenous use Initial U.S. Approval: 2017. Highlights of prescribing information. https://www.emdserono.com/us-en/pi/bavencio-pi.pdf