Amid Setbacks, Lacutamab Cleared to Advance in CTCL Phase 3 Trial by FDA

The FDA has reviewed and cleared the protocol for a confirmatory phase 3 trial of lacutamab (IPH4102) in cutaneous T-cell lymphomas (CTCL), including Sézary syndrome and mycosis fungoides, a group of rare non-Hodgkin lymphomas.¹

The imminent phase 3 TELLOMAK 3 trial is anticipated to launch in the first half of 2026 as a confirmatory follow-up to the phase 2 TELLOMAK trial (NCT03902184), which demonstrated durable activity, favorable safety, and quality of life improvement in patients with CTCL.

Per Innate Pharma, the sponsor, the trial will be assessing the primary end point of progression-free survival (PFS) per blinded central review. The study will include 2 independent cohorts undergoing separate randomization schemes. The first cohort will include patients with Sézary syndrome who previously received mogamulizumab (Poteligeo); here, patients will be randomized 1:1 to receive either lacutamab or romidepsin (Istodax). In the second cohort consisting of patients with mycosis fungoides, patients will be randomly assigned 1:1 to receive either lacutamab or mogamulizumab.

“We are pleased to reach this important milestone for the lacutamab program as we prepare to initiate the confirmatory phase 3 study, TELLOMAK 3,” said Sonia Quaratino, chief medical officer of Innate Pharma, in a news release.¹ “The efficacy and safety data from the TELLOMAK phase 2 trial suggest that lacutamab has the potential to be a game changer in the treatment of CTCL, an orphan disease with a high unmet medical need. Our expert clinical team looks forward to collaborating with CTCL investigators and regulators to start the phase 3 trial in due time.”

Furthermore, positive feedback from the FDA suggested potential for accelerated approval, toward which sponsors intend to progress throughout the phase 3 trial.

“Building on robust phase 2 data from TELLOMAK, this milestone brings us [1] step closer to our next goal, submitting for accelerated approval in Sézary syndrome once the phase 3 trial is underway. We remain deeply committed to advancing this differentiated therapy for patients with CTCL,” added Jonathan Dickinson, CEO of Innate Pharma, in the news release.¹

About Lacutamab

Lacutamab is an anti-KIR3DL2 cytotoxicity-inducing monoclonal antibody in clinical development for the treatment of CTCL and peripheral T-cell lymphoma (PTCL).¹ The FDA has recognized its therapeutic potential in lymphoma through both an orphan drug designation for CTCL and breakthrough therapy designation for Sézary syndrome.¹

However, the agent experienced a setback in its development cycle. In October 2023, the FDA placed a clinical hold on the agent’s investigational new drug (IND) due to a fatal adverse event (AE) of hemphagocytic lymphohistiocytosis, temporarily halting the phase 2 TELLOMAK trial as well as the phase 1b study in PTCL (NCT05321147). The hold was lifted 3 months later.

About the Phase 2 TELLOMAK Trial

The phase 2 TELLOMAK trial is a nonrandomized, open-label, multicenter, multicohort study assessing lacutamab’s clinical activity and safety in relapsed/refractory CTCL.² It has a key primary end point of objective response rate (ORR) and secondary end points of safety, quality of life, PFS, overall survival, pharmacokinetics, immunogenicity, and duration of response.

The study has enrolled 170 heavily pretreated patients who have been included in either a Sézary syndrome cohort (cohort 1) or a mycosis fungoides cohort (cohort 2) as well as cohorts according to KIR3DL2 expression status. All patients have received a 750-mg dose of lacutamab via intravenous infusion every week for 5 weeks, followed by 2 weeks for 10 administrations, then every 4 weeks until disease progression or unacceptable toxicities.

About a year after its launch in May 2019, the trial encountered a roadblock in the first half of 2020 when the FDA placed a partial clinical hold, citing Good Manufacturing Practice deficiencies at a subcontractor manufacturing site. No safety concerns were reported by the FDA in relation to the agent, and the hold was lifted in June 2020.

An early readout of data revealed clinical benefits by lacutamab regardless of KIR3DL2 status. With a median follow-up of 11.8 months, a 16.8% ORR (95% CI, 10.9%-25.0%) was reported for the overall population.³ Longer-term follow-up data of cohort 1 revealed an even higher confirmed ORR of 42.9% (95% CI, 31.4%–55.1%) at a median follow-up of 25.1 months.⁴

Regarding safety, the most common treatment-related treatment-emergent AEs observed in the overall population included fatigue (11.2%), nausea (11.2%), asthenia (10.3%), and arthralgia (10.3%).³

Amidst setbacks in phase 2, the recent clearance for the imminent phase 3 trial marks a strong step forward for lacutamab, reflecting the sponsor’s commitment to ensuring patient safety and delivering the novel agent to patients, as well as the FDA’s belief in the promise of the agent to revolutionize CTCL treatment. Results of the confirmatory trial will be required to definitively establish lacutamab’s potential to drive a long-awaited shift in the CTCL treatment paradigm.

REFERENCES

1. Innate Pharma announces FDA clearance to proceed with TELLOMAK 3, a confirmatory phase 3 trial of lacutamab in CTCL. News release. Innate Pharma. November 10, 2025. Accessed November 11, 2025. https://tinyurl.com/yphn9zvb

2. IPH4102 alone or in combination with chemotherapy in patients with advanced T cell lymphoma (TELLOMAK). ClinicalTrials.gov. Updated November 8, 2024. Accessed November 11, 2025. https://clinicaltrials.gov/study/NCT03902184

3. Porcu P, Bagot M, Ram-Wolff C, et al. Lacutamab in patients with relapsed and/or refractory mycosis fungoides: Results from the TELLOMAK phase 2 trial. J Clin Oncol. 2024;42(suppl 16):7082. doi:10.1200/jco.2024.42.16_suppl.7082

4. Porcu P, Bagot M, Kim YH, et al. Lacutamab in patients with relapsed and refractory Sézary syndrome: Long term follow-up from the TELLOMAK phase 2 trial. J Clin Oncol. 2025;43(suppl 16):2522. doi:10.1200/jco.2025.43.16_suppl.2522