KIR3DL2

Innate announced the decision to not reopen the trial’s recruitment in its full-year earnings report. Image credit: Shutterstock/CI Photos. Innate has dropped plans to evaluate lacutamab as a monotherapy in KIR3DL2-expressing refractory/relapsing peripheral T cell lymphoma (r/r PTCL) following disappointing data from a Phase Ib trial. The French biotech, which has both PTCL and cutaneous T cell lymphoma (CTCL) programmes for its anti-KIR3DL2 antibody, highlighted the “prespecified threshold for meaningful activity not being reached” as the reason for the trial’s (NCT05321147) termination. Innate announced the decision to not reopen the trial’s recruitment in its full-year earnings report released on 21 March. Lacutamab has had a bumpy clinical journey. The US Food and Drug Administration (FDA) placed a partial clinical hold on the drug’s trials in December 2023, following a death from a rare haematologic disorder in one of Innate’s CTCL trials evaluating lacutamab. The hold was lifted a month later after an analysis found that Innate’s compound was not to blame. Whilst it is the end of the road for lacutamab as a monotherapy in PTCL, Innate is still investigating its potential use in the cancer type as a combination with the chemotherapy GEMOX – gemcitabine in combination with oxaliplatin. The Phase II KILT trial (NCT04984837) is being led by the Lymphoma Study Association (LYSA). See Also: AnGes files patent for crispr-based method for modifying mutant lRRK2 gene in cells Cellectis files patent for engineered T-cells for immunotherapy with inhibited B2M expression Innate will also press ahead with its CTCL programme as planned. In December 2023, the biotech reported positive final data for its Phase II TELLOMAK study (NCT03902184) in patients with Sézary syndrome, a type of CTCL. The results included a 37.5% objective response rate in patients treated with a median of five prior lines of therapy. Innate has also reported positive interim data from a Phase I trial investigating the drug in patients with mycosis fungoides (MF), also a type of CTCL. The company expects to present topline results from the study later this year. In the financial results release, Innate’s CEO Hervé Brailly also pointed towards recent successes in its natural killer (NK) cell engager programme. Innate has become somewhat of a specialist in NK cell engagers through its ANKET platform. The biotech has a range of NK-targeting therapies in clinical trials being tested as cancer treatments via a collaboration with Sanofi . The big pharma has licensed four NK cell engagers from Innate through a €400m ($437.5m) initial deal and a €15m ($16.4m) expansion . With a view to Innate’s plans for 2024, Brailly said: “We expect notable milestones including final results from the TELLOMAK Phase II trial with lacutamab in mycosis fungoides, and progressing our first proprietary ADC programme, IPH45 towards an IND filing.”

Plus, news about Evommune, Maruho and Nouscom: Innate Pharma gives up on Phase 1b trial for cancer drug: The company was evaluating lacutamab as a monotherapy in KIR3DL2-expressing refractory/relapsing peripheral T cell lymphoma. Innate said it’s not planning to restart recruitment in the trial after a clinical hold was put into place for studies assessing the drug in PTCL and cutaneous T cell lymphoma after a patient death was reported in the latter. It cited a lack of “meaningful clinical activity” for lacutamab in the PTCL study evaluating the drug as a monotherapy. It is still being studied in combination with chemo in a Phase 2 trial in PTCL. — Katherine Lewin

Innate Pharma disclosed Thursday that it is ending its pursuit of lacutamab as monotherapy in peripheral T-cell lymphoma (PTCL) after the anti-KIR3DL2 antibody fell short in a Phase Ib trial. The setback has prompted the company to refocus its efforts on evaluating lacutamab in combination regimens for this indication.The move comes over two months after the FDA lifted a partial clinical hold on studies of the drug following a patient death in the Phase II TELLOMAK study. That trial is investigating lacutamab in patients with cutaneous T-cell lymphoma (CTCL), including both Sézary syndrome and mycosis fungoides. A review by the FDA subsequently determined that the fatal case was tied to aggressive disease progression and was unrelated to lacutamab, according to Innate.The company noted that "despite objective responses observed" in the monotherapy trial of patients with KIR3DL2-expressing refractory/relapsing PTCL, it will "not be reopened to recruitment as the prespecified threshold for meaningful clinical activity was not reached."Innate suggested it is nevertheless forging ahead with a combination strategy for lacutamab in this indication. The investigator-sponsored Phase II KILT trial is ongoing testing the drug in combination with chemotherapy, versus chemotherapy alone, in patients with KIR3DL2-expressing relapsed/refractory PTCL.Innate highlighted preclinical data presented at last year's American Society of Hematology (ASH) congress pointing to a "synergistic effect" between lacutamab and chemotherapy in preclinical models of PTCL, supporting the rationale for moving forward with a combination strategy.At ASH, Innate also reported final data from the TELLOMAK study, where lacutamab was associated with a global confirmed objective response rate (ORR) of 37.5% in a heavily pre-treated population of patients with Sézary Syndrome. ORRs in the skin and blood were 46.4% and 48.2%, respectively, with median progression-free survival of 8 months.Innate said top-line results from TELLOMAK in mycosis fungoides will be reported at a medical conference this year.