Rozlytrek Rozlytrek

Generic name:

ENTRECTINIB

Company:

GENENTECH INC

FDA approval date:

08/15/2019

Specific treatment:

ROZLYTREK is a kinase inhibitor indicated for the treatment of:
•     Adult patients with metastatic non-small cell lung cancer (NSCLC) whose
tumors are ROS1-positive. (1.1)
•     Adult and pediatric patients 12 years of age and older with solid tumors
that:
o have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion

without a known acquired resistance mutation,

o are metastatic or where surgical resection is likely to result in severe
morbidity, and
o have progressed following treatment or have no satisfactory alternative
therapy.
This indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of clinical
benefit in the confirmatory trials. 

Mechanism of Action:

Entrectinib is an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, and TRKC
(encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes NTRK1, NTRK2, and NTRK3,
respectively), proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK)
with IC50 values of 0.1 to 2 nM. Entrectinib also inhibits JAK2 and TNK2 with IC50 values > 5 nM. The major
active metabolite of entrectinib, M5, showed similar in vitro activity against TRK, ROS1, and ALK.
Fusion proteins that include TRK, ROS1, or ALK kinase domains can drive tumorigenic potential through
hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Entrectinib
demonstrated in vitro and in vivo inhibition of cancer cell lines derived from multiple tumor types
harboring NTRK, ROS1, and ALK fusion genes.
Entrectinib demonstrated steady-state brain-to-plasma concentration ratios of 0.4 – 2.2 in multiple animal
species (mice, rats, and dogs) and demonstrated in vivo anti-tumor activity in mice with intracranial
implantation of TRKA- and ALK-driven tumor cell lines. 

Dosage Form/Route:

Capsules: 100 mg and 200 mg

Side Effects:

The most common adverse reactions (≥ 20%) were fatigue, constipation,
dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia,
cognitive impairment, increased weight, cough, vomiting, pyrexia, arthralgia,
and vision disorders