Date: 2016-02-17
Type of information: R&D agreement
Compound: Halaven® (Eribulin) and PQR309
Company: Eisai (Japan) PIQUR Therapeutics (Switzerland)
Therapeutic area: Cancer - Oncology
Type agreement: R&D clinical research
Action mechanism: mitotic inhibitor/tubulin binder/kinase ihibitor/mTOR inhibitor. Eribulin is a non-taxane, microtubule dynamics inhibitor indicated for the treatment of patients with breast cancer who have previously received at least two chemotherapeutic regimens for metastatic disease and whose prior therapy should have included an anthracycline and a taxane. Eribulin belongs to a class of antineoplastic agents, the halichondrins, which are natural products, isolated from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics without affecting the shortening phase and sequesters tubulin into non-productive aggregates. PQR309 is an orally bioavailable pan inhibitor of phosphoinositide-3-kinases (PI3K) and inhibitor of the mammalian target of rapamycin (mTOR), with potential antineoplastic activity. PQR309 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy. As mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K, this agent may potentially be more potent than an agent that inhibits either PI3K kinase or mTOR kinase. By inhibiting mTOR to a lesser extent than PI3K, PQR309 does not interfere with the mTOR-mediated negative feedback loop on PI3K signaling. Blocking the negative feedback loop would potentially increase PI3K signaling and decrease therapeutic efficacy.
Disease: triple-negative breast cancer (TNBC).
Details: * On February 17, 2016, Eisai and PIQUR Therapeutics announced a landmark agreement to conduct a Phase 1/2b clinical study to investigate PQR309 in combination with Halaven® (eribulin) in patients with triple-negative breast cancer (TNBC).
A significant number of HER2-negative breast cancer patients are expected to have activated PI3K, de novo or induced by prior chemotherapy administration. PQR309 is currently engaged in multiple Phase 1 and Phase 2 studies as a single agent. The combination of a PI3K/mTOR inhibitor with eribulin may prove to be an effective treatment in second line therapy for locally advanced or metastatic TNBC patients.
The Phase 1/2b study is scheduled to begin in early 2016. The initial Phase 1 dose-escalation part of the study will assess the safety and tolerability of PQR309 combined with eribulin in patients with locally advanced or metastatic HER2-negative and triple-negative breast cancer. The Phase 2b expansion part of the study will enroll patients with advanced or metastatic TNBC. The primary objective of this part of the study is to evaluate the efficacy of the PQR309 in combination with eribulin. In total, the Phase1/2b study will enroll approximately 60 patients.
PIQUR will be responsible for conducting the Phase 1/2b clinical trial and the parties may extend the collaboration to include a Phase 3 clinical trial as well as additional trials in new indications of mutual interest.
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