lundi 13 juillet 2020


ADC Therapeutics Presents Interim Phase I Data from its Novel Antibody-Drug Conjugate ADCT-402

Par Rédaction , dans Communiqués , le 11 décembre 2017

Monday, December 11th 2017 at 6:00am UTC

Presented at ASH Annual Meeting

LAUSANNE, Switzerland–(BUSINESS WIRE)– ADC Therapeutics (ADCT), an oncology drug discovery and development
company that specializes in the development of proprietary Antibody Drug
Conjugates (ADCs) targeting major cancers, today announced clinical data
from two ongoing Phase I clinical trials evaluating ADCT-402
(loncastuximab tesirine or “Lonca-T”) in important subtypes of lymphoma
and leukemia. The data were presented at the 59th American
Society of Hematology (ASH) Annual Meeting in Atlanta, USA.

1. Interim results of a Phase I open label, single
agent, dose-escalating study of ADCT-402 evaluating tolerability,
safety, pharmacokinetics and efficacy in patients with relapsed or
refractory B-cell Non-Hodgkin Lymphoma

Dr. Brad Kahl, M.D., Professor for Medical Oncology at the Washington
University School of Medicine in St. Louis, said: “A significant number
of Diffuse Large B-Cell Lymphoma (DLBCL) patients become relapsed or
refractory to existing therapies and have no approved treatment options.
As a result, we are very excited about the 60 percent overall response
rate (ORR) of Lonca-T at 120 µg/kg or higher, including a 35 percent
complete response rate, in this difficult-to-treat patient population.
Although the data are still maturing, we are also very encouraged by a
median duration of response so far of approximately 5 months. Overall,
these results justify the rapid development of the Lonca-T clinical
program to address this unmet need.”

Data were presented from 138 evaluable, heavily pre-treated, patients
who had failed, or were intolerant to, any established therapy known to
provide clinical benefit. The median age of patients was 64 years, and
they had a median of 3 prior therapies. Data were reported from Part 1
and Part 2 of the Phase I study as of November 1, 2017. In Part 1 (dose
escalation), 88 patients were treated at dose ranges from 15-200 µg/kg.
In Part 2 (dose expansion), 50 patients were treated in two cohorts at
either 120 or 150 µg/kg.

Key findings presented at an oral presentation included:

  • For the 68 response-evaluable patients in Part 1 at doses greater than
    or equal to 120 ?g/kg, the ORR was 60 percent (41/68) with 24 patients
    achieving a complete response (35 percent) and 17 patients achieving a
    partial response (25 percent).
  • For the 49 response-evaluable patients in Part 1 with Diffuse Large
    B-Cell Lymphoma at doses greater than or equal to 120 µg/kg the ORR
    was 55 percent (27/49) with 18 patients achieving a complete response
    (37 percent) and 9 patients achieving a partial response (18 percent).
  • ADCT-402 has been reasonably well tolerated.
  • The most common treatment-emergent adverse events of any grade
    occurring in at least 20 percent of patients in Part 1 and Part 2 were
    fatigue (44 percent), nausea (28 percent), elevated
    gamma-glutamyltransferase (27 percent), anemia (25 percent), and
    peripheral edema (25 percent). The most common Grade 3 or 4 adverse
    events occurring in at least 5 percent of patients, regardless of
    attribution, were reduced neutrophil count (15 percent), elevated
    gamma-glutamyltransferase (15 percent), anemia (12 percent), reduced
    platelet count (12 percent), neutropenia (12 percent),
    thrombocytopenia (9 percent), elevated blood alkaline phosphatase (5
    percent), fatigue (5 percent), reduced lymphocyte count (5 percent),
    and reduced white blood cell count (5 percent).
  • Dose expansion in Part 2 of the Phase I study may continue using the
    recommended doses from Part 1 (i.e. 120 or 150 µg/kg).

2. Elucidating Exposure-Response (Safety and
Efficacy) of ADCT-402 (Loncastuximab Tesirine), a Novel
Pyrrolobenzodiazepine-containing Antibody Drug Conjugate, for
Recommended Phase 2 Dose Determination in Patients with Relapsed or
Refractory Non-Hodgkin Lymphoma

This poster presented pharmacokinetic (PK) data elucidating the
relationship between drug exposure and response in terms of safety and
efficacy.

3. Interim results of a Phase I open label, single
agent, dose-escalating study of ADCT-402 evaluating tolerability,
safety, pharmacokinetics and efficacy in patients with relapsed or
refractory B-cell acute lymphoblastic leukemia

Data were presented from 29 evaluable, heavily pre-treated, patients who
had failed, or were intolerant to, any established therapy known to
provide clinical benefit. The median age of patients was 50 years, and
they had a median of 2 prior therapies. Data were reported from Part 1
of the Phase I study as of November 1, 2017. In Part 1 (dose
escalation), patients were treated at dose ranges from 15-150 µg/kg
every three weeks, or at a dose of 50 µg/kg once weekly.

Key findings presented at a poster session included:

  • Four patients achieved a complete bone marrow response.
  • ADCT-402 has been reasonably well tolerated.
  • The most common treatment-emergent adverse events of any grade
    occurring in at least 20 percent of patients were nausea (31 percent),
    fatigue (24 percent), febrile neutropenia (24 percent), and headache
    (24 percent). The most common Grade 3 or 4 adverse events occurring in
    at least 10 percent of patients, regardless of attribution, were
    febrile neutropenia (24 percent), reduced neutrophil count (14
    percent), bacteremia (10 percent), abdominal pain (10 percent), lung
    infection (10 percent), and sepsis (10 percent).
  • Dose escalation will continue using weekly dosing.

About ADCT-402

ADCT-402 is an antibody drug conjugate (ADC) composed of a humanized
monoclonal antibody that binds to human CD19, conjugated through a
linker to a pyrrolobenzodiazepine (PBD)-dimer toxin. Once bound to a
CD19- expressing cell, ADCT-402 is internalized into the cell where
enzymes release the PBD-based warhead. CD19 is a clinically validated
target for the treatment of B-cell malignancies. The PBD-based warhead
has the ability to form highly cytotoxic DNA interstrand cross-links,
blocking cell division and resulting in cell death. ADCT-402 is being
evaluated in two ongoing Phase I clinical trials in patients with
relapsed or refractory B-cell lineage non-Hodgkin lymphoma and relapsed
or refractory B-cell lineage acute lymphoblastic leukemia. (www.adct-402.com)

About ADC Therapeutics

ADC Therapeutics SA (ADCT) is an oncology drug development company that
specializes in the development of proprietary antibody drug conjugates
(ADCs) targeting major types of hematological malignancies and solid
tumors. The Company’s ADCs are highly targeted biopharmaceutical drugs
that combine monoclonal antibodies specific to surface antigens present
on particular tumor cells with a novel class of highly potent
pyrrolobenzodiazepine (PBD) based warheads via a chemical linker. The
Company has four PBD-based antibody drug conjugates in six ongoing Phase
Ia and Ib clinical trials in the USA and in Europe, and a deep pipeline
of other preclinical ADCs in development. ADCT enjoys strong
relationships with world class partners, including AstraZeneca and its
global biologics research and development arm, MedImmune. The Company is
based in Lausanne (Biopôle), Switzerland and has operations in London,
San Francisco and New Jersey. (www.adctherapeutics.com).

Contacts

ADC Therapeutics
Dr. Chris Martin
Chief Executive
Officer
chris.martin@adctherapeutics.com
Tel.:
+41 (0) 21 653 0200
or
Alexandre Müller
Dynamics Group
amu@dynamicsgroup.ch
Tel:
+41 (0) 43 268 3231

Source: ADC Therapeutics

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