Date: 2016-01-11
Type of information: Clinical research agreement
Compound: INCB39110 and Tagrisso® (osimertinib)
Company: Incyte (USA - DE) AstraZeneca (UK)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: kinase inhibitor/tyrosine kinase inhibitor/janus kinase inhibitor/JAK inhibitor. Tagrisso® (AZD9291/osimertinib) is an irreversible inhibitor of epidermal growth factor receptors that harbour sensitising mutations (EGFRm) and TKI-resistance mutation T790M. Nearly two out of three patients with NSCLC whose disease progresses after treatment with an EGFR inhibitor develop the T790M mutation, for which treatment options are limited. A small number of patients (approximately 3-5%) have the T790M mutation at NSCLC diagnosis.
INCB39110 is an orally bioavailable, isoform-selective inhibitor of Janus-associated kinase 1 (JAK1). JAK1 activity is believed to play an important role in both autoimmune and oncologic diseases. JAK1 forms heterodimeric complexes with JAK2, JAK3 or TYK2 and functions as an immunomodulatory and inflammatory signalling kinase. Selective JAK1 inhibition prevents STAT signaling downstream of a number of cytokines, including IL-6, IL-10 and interferon-gamma. INCB39110 will be investigated in clinical trials as monotherapy in graft versus host disease (GvHD) and in several combination-based therapeutic regimens, including with PI3Kd (INCB50465), IDO1 (epacadostat) and EGFR (Tagrisso) inhibitors.
Disease: EGFR mutation-positive non-small cell lung cancer (NSCLC)
Details:
- • On January 11, 2016, Incyte Corporation and AstraZeneca announced a new collaboration to evaluate the efficacy and safety of Incyte\'s Janus-associated kinase (JAK) 1 inhibitor, INCB39110, in combination with AstraZeneca\'s next generation epidermal growth factor receptor (EGFR) inhibitor, Tagrisso® (osimertinib). The combination will be assessed as a second-line treatment for patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), who have been treated with a first generation EGFR tyrosine kinase inhibitor (TKI) and subsequently developed the T790M resistance mutation.
There is increasing evidence that signaling through the JAK-STAT (signal transducer and activator of transcription) pathway could be a contributing factor in resistance to EGFR TKI treatment in patients with EGFR mutation NSCLC. Blocking both JAK and EGFR activity may therefore offer an improved targeted treatment benefit in some patients.
Under the terms of the agreement, AstraZeneca and Incyte will collaborate on a Phase 1/2 study, to be conducted by Incyte . The Phase 1 part of the trial is expected to establish a recommended dose regimen for the combination of INCB39110 and Tagrisso® while the Phase 2 part of the study will assess the safety and efficacy profile. Results from the study will be used to determine whether further clinical development of this combination is warranted.
This agreement builds on an existing collaboration between the two companies, announced in May 2014 , to explore AstraZeneca\'s anti-PD-L1 immune checkpoint inhibitor, durvalumab, in combination with Incyte\'s oral indoleamine dioxygenase-1 (IDO1) inhibitor, epacadostat (INCB24360).
Financial terms:
Latest news:
Is general: Yes
