How Immutep’s LAG-3 Trials Are Reshaping Lung and Head & Neck Cancer Treatment

Immutep’s Clinical Momentum in Oncology

Immutep Limited (ASX – IMM; NASDAQ – IMMP) continues to build momentum in its clinical-stage immunotherapy programs, reporting significant progress in the quarter ended June 30, 2025. The company’s pivotal TACTI-004 Phase III trial, evaluating eftilagimod alfa (efti) combined with KEYTRUDA® and chemotherapy in first-line non-small cell lung cancer (NSCLC), is expanding rapidly with 78 activated sites across 23 countries. This global trial aims to enroll approximately 756 patients, positioning Immutep to potentially secure marketing approval in one of oncology’s largest indications.

Complementing this, the investigator-initiated INSIGHT-003 Phase I trial in non-squamous NSCLC reported a compelling 60.8% response rate and 90.2% disease control rate among 51 patients. Notably, patients with tumor proportion score (TPS) below 50%, representing a majority of the NSCLC population, achieved a 59.6% response rate, significantly higher than historical controls of 40.8% with KEYTRUDA® and chemotherapy alone. Safety profiles remain favorable, with no new concerns emerging.

Advances in Head and Neck and Soft Tissue Sarcoma Trials

In head and neck squamous cell carcinoma (HNSCC), the TACTI-003 Phase IIb trial’s Cohort B demonstrated a median overall survival of 17.6 months in patients with low PD-L1 expression (CPS <1). This outcome compares favorably to current standard-of-care therapies, which typically yield median survivals between 7.9 and 11.3 months. Immutep has proactively engaged the U.S. FDA to discuss regulatory pathways, signaling confidence in these data.

Meanwhile, the EFTISARC-NEO Phase II trial in resectable soft tissue sarcoma met its primary endpoint, showing a significant increase in tumor hyalinization and fibrosis when efti was combined with radiotherapy and KEYTRUDA®. This investigator-initiated study, supported by the Polish Medical Research Agency, underscores Immutep’s expanding footprint in diverse oncology indications.

Progress in Autoimmune Disease and Intellectual Property

Beyond oncology, Immutep’s autoimmune candidate IMP761, a first-in-class LAG-3 agonist antibody, reported encouraging initial pharmacological data from its Phase I trial. At the highest dosing level tested (0.9 mg/kg), IMP761 achieved 80% inhibition of T cell infiltration in skin following neoantigen rechallenge, with no treatment-related adverse events observed. These findings highlight the therapeutic potential of modulating immune checkpoints to treat autoimmune diseases.

Intellectual property protection was bolstered with four new patents granted across multiple jurisdictions, including New Zealand, the Philippines, and Korea, covering both efti and IMP761. This strengthens Immutep’s competitive position as it advances its pipeline.

Financial Health and Corporate Developments

Immutep reported a strong cash position of approximately A$129.69 million, combining cash, equivalents, and term deposits. This robust funding base supports an expected cash runway through to the end of calendar year 2026, enabling continued investment in clinical programs without immediate capital raises. Operating cash outflows increased in line with intensified trial activity, with research and development expenses rising to A$15.66 million in the quarter.

On the corporate front, Stephan Winckels M.D., Ph.D., was appointed permanent Chief Medical Officer, bringing over 15 years of oncology drug development experience and continuity in overseeing efti trials. Additionally, the company eliminated convertible debt and warrants following a cashless exercise by Ridgeback Capital Investments, simplifying its capital structure.