Clinical Trials

Date: 2018-09-29

Type of information: Presentation of results at a congress

phase: 1

Announcement: presentation of results at the EORTC Cutaneous Lymphoma Group meeting

Company: Innate Pharma (France)

Product: IPH4102

Action mechanism:

  • monoclonal antibody.  KIR3DL2 is an inhibitory receptor of the KIR family, normally expressed on a subset of normal NK cells and specifically expressed in most subtypes of the orphan indication of CTCL. CTCL is a group of rare cutaneous lymphomas of T lymphocytes with poor prognosis and few therapeutic options at advanced stages, such as the Sezary Syndrome and Transformed Mycosis Fungoides. IPH4102 is a first-in-class anti-KIR3DL2 humanized cytotoxic antibody, designed to selectively deplete CTCL cancer cells. IPH4102 was recently granted orphan drug status in the European Union for the treatment of CTCL. Biomarker tools are being developed in parallel to monitor KIR3DL2 expression in patients

Disease: cutaneous T-cell lymphoma (CTCL) and especially their aggressive forms: Sezary Syndrome and Transformed Mycosis Fungoides

Therapeutic area: Cancer - Oncology - Rare diseases

Country: France, The Netherlands, UK, USA

Trial details:

  • The Phase I trial is an open label, multicenter study of IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas which is performed in Europe (France, Netherlands, United Kingdom) and in the US. Participating institutions include several hospitals with internationally recognized expertise: the Saint-Louis Hospital (Paris, France), the MD Anderson Cancer Center (Houston, Texas), the Stanford University Medical Center (Stanford, CA), the Ohio State University (Columbus, OH), the Leiden University Medical Center (Netherlands), and the Guy’s and St Thomas’ Hospital (United Kingdom). Pr Martine Bagot, Head of the Dermatology Department at the SaintLouis Hospital, Paris, is the principal investigator of the trial.
  • Approximately 60 patients with KIR3DL2-positive CTCL having received at least two prior lines of systemic therapy are expected to be enrolled in two sequential study parts:
  • - A dose-escalation part including approximately 40 CTCL patients in 10 dose cohorts. Its objective is to identify the Maximum Tolerated Dose and/or the Recommended Phase 2 Dose (RP2D);
  • - A cohort expansion part with 2 cohorts of 10 patients each in 2 CTCL subtypes (transformed mycosis fungoides and Sézary syndrome) receiving IPH4102 at the RP2D until progression. The CTCL subtypes may be adjusted based on the findings in the dose escalation part of the study.
  • The primary objective of this trial is to evaluate the safety and tolerability of IPH4102 in this patient population. The secondary objectives include assessment of the drug’s antitumor activity and identification of biomarkers of this activity. Clinical endpoints include overall objective response rate, response duration and progression-free survival. (NCT02593045)

Latest news:

  • • On September 29, 2018, Innate Pharma announced new data from the Phase I clinical trial of IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas (CTCL). The data, including longer follow up for patients treated in the dose-escalation and observations from an additional patient cohort, have been presented at the EORTC Cutaneous Lymphoma Group meeting in St. Gallen, Switzerland, by Pr Martine Bagot. “These data support the positive trends observed in the dose-escalation part of the trial and demonstrated a high response rate and long progression-free survival for these heavily pretreated CTCL patients, a majority being Sézary syndrome,” commented Pierre Dodion, Chief Medical Officer of Innate Pharma. “Additionally, these data will serve as a basis for the initiation of a broader Phase II clinical program in Sézary syndrome and other subtypes of T-cell lymphomas.”
  • As of June 28, 2018, a total of 44 patients with relapsed/refractory CTCL were evaluable for safety and clinical activity. The study consisted of two parts: a dose-escalation (n=25) and a cohort expansion (n=19). Patients received a median of 3 prior systemic therapies. IPH4102 demonstrated a favorable safety profile and was well-tolerated. The study showed clinical activity that was demonstrated by a high response rate and long progression free survival. In the total study population, the objective response rate (ORR) was 36% and median duration of response (DOR) and progression free survival (PFS) were 13.8 and 8.2 months, respectively. Sézary syndrome (SS) subset patients treated in the dose-escalation part (n=20) now show median PFS of close to 1 year. At the cut-off date of June 28, 2018, median followup was 12.7 months and nine patients were still ongoing treatment. Better outcomes were observed in patients without evidence of histologic large cell transformation (LCT) (n=29); these patients achieved an ORR of 51.7% and PFS of 12.8 months. LCT is present in approximatively 10% of all Mycosis fungoides/Sézary syndrome patients and is associated with poorer prognosis and shorter survival using currently available therapies.
  • • On October 16, 2017, Innate Pharma announced that final results of the dose-escalation part of the ongoing Phase I study investigating IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas (CTCL), an orphan disease, were presented by Pr Martine Bagot, Principal Investigator and Head of the Dermatology Department at the Saint-Louis Hospital, Paris, in an oral presentation at the EORTC CLTF1 Meeting in London on October 15, 2017. These data confirm the good safety profile and promising activity of IPH4102 in this elderly and heavily pretreated patients population (n=25). The objective response rate in the 20 patients with Sézary syndrome was 50%; the ORR42 was 40%, the disease control rate (DCR), 90%, the median duration of response (DOR), 9.9 months and the median progression free survival (PFS), 10.8 months, respectively. Data on pruritus were reported for the first time and show substantial improvement in patients having a global clinical response but also in patients with stable disease. The Recommended Phase 2 Dose (RP2D) has been identified at 750 mg, a fixed dose equivalent to 10 mg/kg.
  • Expansion cohorts started, including 2 cohorts of 15 patients each in two CTCL subtypes: Sézary syndrome and transformed mycosis fungoides. Biomarker results were presented in an oral presentation by Dr Maxime Battistella, Assistant Professor Pathology and Dermatopathology at St Louis Hospital and Université L. Diderot.
  • On October 26, 2016, Innate Pharma announced preliminary safety and clinical activity results from the dose-escalation part of the Phase I study testing IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas. These data are presented in a poster at the Third World Congress of Cutaneous Lymphomas (October 26-28, 2016, New-York, USA). The Phase I study is currently ongoing. Data are reported for the first seven dose levels (0.0001 to 1.5 mg/kg, 16 patients) of the dose-escalation part. In this population, IPH4102 was well-tolerated with no dose-limiting toxicity reported. The majority of adverse events is typical for CTCL or reflects low grade infusion-related reactions. As of September 10, 2016, the best global response rate was 38% across all dosage levels. Complete responses appeared with increasing doses and/or duration of exposure in skin and blood (respectively 2 and 3, seen in 4 patients)[1]. All responses are ongoing at the time of the analysis, which occurred after a median duration of treatment of 126+ days (range of 41+ to 298+).
  • Three additional dose levels (3, 6 and 10 mg/kg) remain to be evaluated and the dose escalation part of the trial is now expected to be completed by Q2 2017 (previously expected at the end of 2017). The study started enrolling patients in November 2015. So far, 16 patients with KIR3DL2-positive CTCL have been enrolled in seven dose-cohorts, including 13 patients with Sézary syndrome, 2 patients with mycosis fungoides and 1 patient with CD4+ CTCL. Median age was 71 years and patients had received 2 to 8 lines of prior systemic therapy for their disease.All of the 16 patients treated with IPH4102 were evaluable for safety and clinical activity assessments.
  • As of September 10, 2016, patients had received up to 18 administrations of IPH4102. Treatment is ongoing in 12 patients. Preliminary results of exploratory endpoints such as pharmacodynamics in skin and blood are in line with clinical activity results (see poster #O-11), and show depletion of KIR3DL2-expressing tumor cells in skin and blood of patients after IPH4102 administrations.
  • • On June 5, 2016, Innate Pharma announced that Professor Martine Bagot, Head of the Dermatology Department at the Saint-Louis Hospital in Paris discussed the protocol of the ongoing first in human study of IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas (CTCL) in a “Trial in progress” poster at the 2016 ASCO1 annual meeting (June 3-7, 2016, in Chicago, USA). The primary objective of this trial is to evaluate the safety and tolerability of repeated administrations of single agent IPH4102 in this patient population. The secondary objectives include assessment of the drug’s antitumor activity. A large set of exploratory analyses aims at identifying biomarkers of clinical activity. Clinical endpoints include overall objective response rate, response duration and progression-free survival. This trial is expected to deliver data for the dose escalation and cohort expansion at the end of 2017 and 2018 respectively.
  • • On December 3, 2015, Innate Pharma announced that a first patient has been dosed in the Phase I clinical trial of IPH4102 in patients with  relapsed/refractory cutaneous T-cell lymphomas. Pierre Dodion, Chief Medical Officer of Innate Pharma, said: “The program has benefited from constant collaboration with Saint-Louis Hospital (Paris, France), and especially with Pr. Martine Bagot, Head of the Dermatology Department and co-discoverer with Pr. Armand Bensussan of the target KIR3DL2. Now, with the involvement of additional international expert centers in Europe and the USA, we believe that we are in optimal conditions to bring this exciting drug to patients with a high unmet medical need”. Hervé Brailly, CEO and co-founder of Innate Pharma, added: “From a strategic point of view, IPH4102 is an important addition to and diversification of our pipeline: it is our first cytotoxic antibody, aiming at depleting KIR3DL2 expressing cells. Developing it in a targeted patient population with an associated biomarker points to a very straightforward path to potentially reach regulatory approval. This prompts our interest in keeping the full rights to develop this drug and eventually market it on our own”.
  • This Phase I trial comprises a dose escalation and a cohort expansion, which are expected to deliver data at the end of 2017 and 2018 respectively. The program was presented in New York during a Key Opinion Leader event chaired by Pr. Youn H. Kim, MD, Professor of Dermatology, Director of the Multidisciplinary Cutaneous Lymphoma Program and Medical Director of the Photopheresis Service at the Stanford Medical Center, as well as in Paris during a Key Opinion Leader event chaired by Pr. Martine Bagot.

Is general: Yes