Immutep's Dosage Optimization in Lung Cancer Immunotherapy: A Catalyst for Accelerated Growth

The landscape of lung cancer treatment is undergoing a transformative shift, driven by advancements in immunotherapy. Among the most promising developments is Immutep's eftilagimod alfa (efti), a first-in-class MHC Class II agonist, which has demonstrated significant potential in optimizing immunotherapy regimens. Recent clinical and regulatory milestones suggest that dosage optimization of efti could serve as a critical catalyst for accelerating both clinical validation and commercial adoption.

A Strategic Dose: The 30 mg Milestone

Immutep's TACTI-004 Phase III trial, initiated in March 2025, marks a pivotal step in the company's lung cancer strategy. The trial evaluates a 30 mg subcutaneous dose of efti in combination with Merck's KEYTRUDA® (pembrolizumab) and chemotherapy for first-line non-small cell lung cancer (1L NSCLC), as described in FDA feedback (https://www.cancernetwork.com/view/fda-gives-positive-feedback-on-phase-3-eftilagimod-alfa-nsclc-trial-design). This dosage was selected based on prior studies and regulatory feedback, including confirmation from the FDA in October 2025 that 30 mg represents the optimal biological dose under Project Optimus. The decision to standardize this dose reflects a balance between efficacy and safety, as evidenced by favorable outcomes in earlier trials like INSIGHT-003, where the triple combination achieved a 60.8% response rate and 90.2% disease control rate in 1L NSCLC patients according to the INSIGHT-003 results.

The 30 mg dose also aligns with the broader goal of addressing PD-L1-negative or low-expressing populations, a subgroup with limited treatment options. Regulatory bodies, including the FDA and the Paul-Ehrlich-Institut (PEI), have provided constructive feedback on the TACTI-004 design, supporting enrollment of approximately 750 patients regardless of PD-L1 status, according to constructive regulatory feedback (https://www.biospace.com/immutep-receives-constructive-regulatory-feedback-on-tacti-004-registrational-trial-in-metastatic-non-small-cell-lung-cancer). This inclusive approach not only broadens the potential market but also strengthens the statistical power of the trial, which has dual primary endpoints of progression-free survival (PFS) and overall survival (OS), as previously reported by the Cancer Network.

Regulatory Momentum and Strategic Pathways

Regulatory engagement has been instrumental in shaping Immutep's clinical strategy. The FDA's endorsement of the 30 mg dose under Project Optimus-a program aimed at streamlining drug development-positions efti for expedited pathways, including potential accelerated approval, as noted in the Stocktitan announcement. Similarly, the PEI's feedback in December 2023 validated the trial's design flexibility, allowing for both chemotherapy-free and triple-combination regimens, as outlined in the Biospace report. These interactions underscore the growing confidence in efti's safety profile, particularly when combined with anti-PD-1 therapies, and highlight the regulatory feasibility of a streamlined biologics license application (BLA) process.

The TACTI-004 trial's design, confirmed by the FDA in July 2024, includes a pre-specified futility boundary and interim analysis, further enhancing its robustness, as reported by the Cancer Network. Such features are critical for attracting investor confidence, as they reduce the risk of late-stage failures and provide early signals of efficacy.

Early Data and Market Implications

Early-phase data from the INSIGHT-003 and TACTI-003 trials have already demonstrated efti's potential to disrupt the lung cancer space. In TACTI-003, the combination of efti with KEYTRUDA® in head and neck squamous cell carcinoma (HNSCC) showed improved overall response rates (ORRs) across all PD-L1 expression levels, including in PD-L1-negative patients, as reported by the Cancer Network. While this trial focused on a different indication, it reinforces the hypothesis that efti can enhance immunotherapy outcomes in populations traditionally resistant to checkpoint inhibitors.

For NSCLC, the 60.8% response rate observed in INSIGHT-003 is particularly compelling, given the standard of care's limitations in advanced-stage disease. If TACTI-004 replicates or exceeds these results, efti could emerge as a cornerstone of first-line treatment, particularly for patients who do not respond to PD-1/PD-L1 inhibitors alone. The global lung cancer market, projected to exceed $25 billion by 2030, offers a vast commercial opportunity for a therapy that addresses unmet needs in PD-L1-negative cohorts .

Conclusion: A Convergence of Science and Strategy

Immutep's progress in lung cancer immunotherapy exemplifies the power of dosage optimization as a catalyst for innovation. By securing regulatory alignment on the 30 mg dose and demonstrating robust early efficacy, the company has positioned itself to accelerate clinical validation and commercialization. The TACTI-004 trial, with its global scale and inclusive design, represents not just a scientific milestone but a strategic inflection point for Immutep. Investors should closely monitor interim results and regulatory updates, as these could redefine the competitive landscape for lung cancer immunotherapy in the coming years.