Swedish Alligator Bioscience, a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, published results from a clinical phase I first-in-human study of the drug candidate ADC-1013 (JNJ-64457107).

Currently, Janssen Biotech, Inc. performs a phase I dose-escalation clinical study (NCT02829099) with intravenous administration of ADC-1013. This study is ongoing with approximately 50 patients recruited to date.

Well tolerated
The investigational compound, intended for immunotherapy of different types of cancer, is a human, monospecific, agonistic, IgG1 antibody targeting the co-stimulatory receptor CD40.

The study results from a multicenter, open-label phase I study (NCT02379741) in patients with late stage solid tumors no longer responding to standard treatment evaluating safety and tolerability, pharmacokinetics, immunogenicity, biomarker response and clinical response. The study is a dose-escalation study, involving intratumoral (22.5-400 ?g/kg) and intravenous (75 ?g/kg) administration of ADC-1013 at five hospitals in Sweden, Denmark and the UK. The study was performed by Alligator and includes 24 enrolled patients and ten different tumor types

Overall, the results show that ADC-1013 is generally well tolerated and support further clinical development of ADC-1013 as a mono- or combination therapy. The data were presented in an oral and poster presentation at the Society for Immunotherapy of Cancer (SITC) 32nd Annual Meeting in National Harbor, Maryland, US, on 10 and 11 November 2017.

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Pre-clinical development
Earlier in the development, pre-clinical data have shown that the ADC-1013 antibody effectively activates T-cells, mediated through binding to the co-stimulatory receptor CD40 on dendritic cells. The increased T-cell activation enables the immune system to attack the cancer. In addition, since some cancer cells express CD40 on the surface, ADC-1013 may act also through a secondary mechanism of action killing cancer cells directly.

In August 2015, Alligator licensed global development rights for ADC-1013 (JNJ-64457107) to Janssen Biotech.

Continued progress
“We are very excited about the continued progress and promising early data of ADC-1013”, said Per Norl?n, CEO at Alligator Bioscience.

“The data indicate that it is well tolerated at clinically relevant doses. There is clear evidence supporting activation of CD40 receptors, which together with the clinical observations give us increased confidence for the continued clinical development of ADC-1013,” Norl?n added.

A total of 23 patients were treated with ADC-1013, either intratumorally or intravenously. Focus on this study was on intratumoral administration, with only five patients receiving ADC-1013 intravenously.

Alligator’s partner Janssen Biotech, is currently performing a phase I dose-escalation study investigating intravenous administration of ADC-1013.

Adverse events
Adverse events throughout the study were primarily fatigue, pyrexia, nausea and vomiting, and were mostly CTCAE Grade 1 or 2 and transient. Intratumoral administration of ADC-1013 into superficial metastases was well tolerated at doses up to at least 400 ?g/kg. Two patients experienced dose limiting effects (grade 3 abdominal pain) at 400 ?g/kg after injections into deeper (i.e. hepatic) lesions.

Secondary outcome measures on tumor efficacy included a best overall response of stable disease for at least 12 months in one patient who received 400 ?g/kg intratumorally into a superficial lesion with intraindividual dose escalation up to 900 ?g/kg.

Last Editorial Review: November 11, 2017

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