FDA Places Partial Clinical Hold on Lacutamab Lymphoma IND Application

The FDA previously placed a partial clinical hold on the TELLOMAK trial due to inadequate Good Manufacturing Practice (GMP) procedures at the developer’s manufacturing subcontractor site in January 2020.

The FDA has placed a partial clinical hold an investigational new drug application for lacutamab as a treatment option for patients with cutaneous T-cell lymphoma (CTCL), resulting in an enrollment pause for the phase 2 TELLOMAK trial (NCT03902184) and phase 1b IPH4102-102 trial (NCT05321147) in those with peripheral T-cell lymphoma (PTCL), according to a press release from Innate Pharma.¹

The regulatory agency placed a hold on these trials following a report of a fatal incidence of hemophagocytic lymphohistiocytosis. Patients who are already deriving benefit from lacutamab are eligible to continue therapy in these trials after reconsenting.

Investigators previously reached a full enrollment of 170 patients for the TELLOMAK trial in the second quarter of 2023. Additionally, 20 patients have enrolled on the initial cohort of the phase 1b IPH4102-102 trial, which will proceed to the next stage of assessment following a futility interim analysis. Final data from the TELLOMAK trial and preliminary findings from the phase 1b IPH4102-102 trial are expected to be shared in the fourth quarter of 2023.

“Patient safety is of paramount importance to us, and we are currently undertaking efforts to address the FDA requests, which include incorporation of risk mitigation and management strategies for hemophagocytic lymphohistiocytosis in ongoing lacutamab studies,” Mondher Mahjoubi, chief executive officer at Innate Pharma, said in the press release. “Additionally, with all patients recruited into the phase 2 TELLOMAK study, we do not currently anticipate any delay for the TELLOMAK phase 2 final data due shortly.”

Developers designed lacutamab as an anti-KIR3DL2 antibody for the management of CTCL and PTCL. According to the press release, KIR3DL2 is expressed in approximately 65% of patients across all CTCL subtypes and up to 90% with aggressive CTCL subtypes including Sézary syndrome.

Investigators of the international, open-label phase 2 TELLOMAK trial are assessing lacutamab as a treatment for patients with CTCL across 4 cohorts. The trial is evaluating lacutamab monotherapy in approximately 60 patients with Sézary syndrome previously treated with 2 previous lines of therapy, in those with mycosis fungoides that express KIR3DL2, in those with mycosis fungoides that do not express KIR3DL2, and in all-comers. All patients have been receiving lacutamab at a flat dose of 750 mg.

The TELLOMAK trial’s primary end point is objective response rate. Secondary end points include treatment-emergent adverse effects, quality of life, overall survival, duration of response, and pharmacokinetics.

In the phase 1b trial, investigators are evaluating treatment with lacutamab alone in patients with relapsed/refractory PTCL expressing KIR3DL2 previously treated with 1 or more lines of systemic therapy. Patients will receive lacutamab intravenously at 750 mg every week for 5 weeks then every 2 weeks for 10 doses followed by every 4 weeks until disease progression or unacceptable toxicity.

The trial’s primary outcome is safety. Investigators are also assessing clinical outcomes, immunogenicity, and pharmacokinetics.

The FDA previously placed a partial clinical hold on the TELLOMAK trial due to inadequate Good Manufacturing Practice (GMP) procedures at the developer’s manufacturing subcontractor site in January 2020.² Following a review of a new GMP-certified batch of lacutamab, the regulatory agency lifted the partial clinical hold in June 2020.³

References

1. Innate Pharma provides update on lacutamab clinical program. News release. Innate Pharma. October 5, 2023. Accessed October 6, 2023. https://bit.ly/3LOxwa3
2. Innate Pharma provides update from regulatory agencies on lacutamab TELLOMAK trial. News release. Innate Pharma. January 9, 2020. Accessed October 6, 2023. https://shorturl.at/eBKS7
3. U.S Food and Drug Administration lifts partial clinical hold on lacutamab TELLOMAK trial in advanced T-cell lymphomas. News release. Innate Pharma. June 24, 2020. Accessed October 6, 2023. https://shorturl.at/bvyW8