Cutaneous T-cell lymphoma (CTCL) presents as a rare form of non-Hodgkin’s lymphoma, with Mycosis Fungoides (MF) representing the majority of cases at 50-60%, followed by Sezary Syndrome, accounting for 2-5% of cases. Unfortunately, advanced-stage MF patients face limited therapeutic options. Lacutamab, a pioneering anti-KIR3DL2 humanized cytotoxicity-inducing antibody currently under clinical investigation for CTCL and peripheral T cell lymphoma (PTCL). In a landscape where effective treatments are scarce, Lacutamab offers hope, showcasing impressive efficacy and outstanding tolerability in heavily treated patients.

Exciting developments unfolded in January 2024 when Innate Pharma announced the lifting of the partial clinical hold on Lacutamab's investigational new drug (IND) application by the US FDA. This decision, following a comprehensive review of a fatal case, deemed the event unrelated to Lacutamab, marking a significant step forward. However, on October 5, 2023, Innate Pharma faced a setback when the Lacutamab IND was temporarily placed on partial clinical hold by the FDA due to a patient death in the TELLOMAK study. Despite this, Lacutamab holds promise as a potential breakthrough in mycosis fungoides treatment, ongoing vigilance and regulatory cooperation remain crucial in ensuring its safe and effective use. The results presented at ASCO 2024 were the following:

Efficacy outcomes 

As of October 13, 2023, data cutoff, MF patients received a median of 4 prior systemic therapies and had a median follow-up of 11.8 months. The data demonstrate that treatment with lacutamab resulted in meaningful antitumor activity, regardless of the KIR3DL2 baseline expression, and an overall favorable safety profile. The global objective response rate (ORR) was 16.8% (Olsen 2011) and 22.4% (Olsen 2022), including 2 complete responses (CR) and 16 partial responses (PR). In patients expressing a baseline KIR3DL2 ≥ 1%, the ORR was 20.8% (Olsen 2011) and 29.2% (Olsen 2022). Median progression-free survival was 10.2 months for all MF patients and 12.0 months in the KIR3DL2 ≥ 1% group. Time to response was 1.0 months.

Safety result: 

• Promising clinical activity of lacutamab regardless of KIR3DL2 expression, with a favorable safety and tolerability profile

• The most common TR TEAEs were fatigue, nausea, asthenia, and arthralgia.

KOL insights

“The anti-tumor activity observed in the Phase II TELLOMAK trial confirms that treatment with lacutamab achieves clinically meaningful outcomes for heavily pretreated patients with mycosis fungoides regardless of baseline KIR3DL2 expression level.” –Chief Medical Officer.

“Mycosis fungoides patients have few efficacious and safe therapeutic options at advanced stages. It is promising to see lacutamab achieving remarkable efficacy along with excellent tolerability in this heavily pre-treated population.”–Professor at Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation.

Conclusion- 

In the TELLOMAK study, data from a heavily pre-treated population with Mycosis Fungoides (MF) affirms the promising clinical activity of Lacutamab, irrespective of KIR3DL2 expression, while maintaining a favorable safety and tolerability profile. These findings strongly advocate for the continued development of Lacutamab, aiming to provide enhanced therapeutic options for patients with Cutaneous T-cell lymphomas (CTCL). The significant anti-tumor activity observed in the Phase II TELLOMAK trial underscores Lacutamab's ability to deliver clinically meaningful outcomes for heavily pretreated MF patients, regardless of their baseline KIR3DL2 expression levels. Consequently, these results provide solid support for the ongoing advancement of Lacutamab towards delivering improved treatments for individuals with CTCL.