Immutep Limited has received positive and constructive feedback from the US Food and Drug Administration regarding the future clinical development of its first-in-class MHC Class II agonist, eftilagimod alfa (efti), for first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma patients with PD-L1 expression below 1 (Combined Positive Score [CPS] <1).
FDA Supports Combination Therapy Development
Based on its review of encouraging data from the TACTI-003 (KEYNOTE-C34) Phase IIb trial evaluating efti in combination with MSD's anti-PD-1 KEYTRUDA (pembrolizumab), the FDA agreed on the potential of the combination to address the high unmet need in this CPS <1 patient segment and is supportive of the combination's further development.
The FDA outlined paths for future clinical development and potential accelerated approval in light of the FDA's Project FrontRunner initiative. These include a randomized registrational trial evaluating efti in combination with KEYTRUDA against standard-of-care therapy, or alternatively a smaller single-arm study with 70-90 patients using safety, response rate, and duration of response as key endpoints, followed by a confirmatory randomized study that builds on existing data.
Addressing Significant Unmet Medical Need
Patients with CPS <1 in first-line HNSCC represent a treatment population with high unmet medical need. Up to 20% of first-line HNSCC patients have CPS <1, and despite immunotherapy's progress in fighting cancer, anti-PD-1 therapy alone (without chemotherapy) is only approved for patients who express PD-L1 (CPS >1). All currently available treatment options for patients with PD-L1 CPS <1 include chemotherapy.
"We are pleased with the FDA's feedback and guidance that underscores the high unmet need of head and neck cancer patients whose PD-L1 expression level is below one," said Marc Voigt, CEO of Immutep. "The FDA feedback positions Immutep to evaluate options for future collaborative clinical development paths to bring a new, effective and safe treatment option to this underserved patient population."
Strategic Focus and Future Development
While acknowledging the positive feedback for head and neck cancer development, Voigt emphasized that the company's primary focus remains the pivotal TACTI-004 Phase III trial evaluating efti as first-line therapy for non-small cell lung cancer. "This focus and additional considerations will be reviewed internally and discussed with stakeholders and potential strategic partners in regards to forward paths in head and neck cancer," he added.
Project FrontRunner Initiative
Project FrontRunner is an FDA Oncology Center of Excellence initiative designed to encourage drug sponsors to consider developing and seeking approval of cancer drugs for advanced/metastatic disease in earlier clinical settings, rather than the usual approach of developing treatments for patients who have received numerous prior therapies or exhausted available treatment options. In this setting, advancing new effective therapies has the greatest potential to significantly improve quantity and quality of patients' lives.
Immutep is a late-stage biotechnology company developing novel immunotherapies for cancer and autoimmune disease, pioneering the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3). The company's diversified product portfolio harnesses LAG-3's ability to stimulate or suppress the immune response.
