Synta plans cautious approach to Phase III for its HSP inhibitor
This article was originally published in Scrip
Synta Pharmaceuticals is sufficiently encouraged by interim Phase II data for its heat shock protein inhibitor ganetespib (STA-9090) in non-small cell lung cancer to take the product into a Phase IIb/III trial in this indication next quarter. The promising results are a boon for the company which suffered disappointment with its former lead product elesclomol in melanoma and they will strengthen its hand as it seeks a licensing partner.
The interim Phase II data show that when given as a single agent, ganetespib produced objective and durable responses in patients with advanced relapsed/refractory NCSLC, with a favourable safety profile, the company said. Responses by such advanced patients to single-agent therapy are rare.
Synta notes that the small molecule ganetespib is structurally unrelated to earlier HSP inhibitors such as 17-AAG, and had broader activity in preclinical studies. In addition, to its own anticancer activity, inhibiting HSP enhances the activity of taxanes by increasing cytotoxicity and preventing resistance; in preclinical models there was potent synergistic activity between ganetespib and docetaxel.
The Phase IIb/III study will compare a combination of ganetespib plus docetaxel vs docetaxel alone in patients with stage IIIB or IV NSCLC who have completed one prior systemic therapy for advanced disease. "Combining ganetespib and docetaxel is a two-punch strategy for improving efficacy of single-agent docetaxel," said Synta's senior vice-president and chief medical officer Dr Vojo Vukovic.
The programme is designed to mitigate risk in the Phase III portion by evaluating biomarkers and other patient characteristics in the Phase IIb portion to help identify those patients most likely to respond.
President and CEO Dr Safi Bahcall added that he was confident of concluding at least one partnership agreement this year for its oncology programmes and the company expects to sign partnerships that "contribute substantial resources and complementary activities to our programmes".
The Phase II results to date show that of 33 evaluable patients, three achieved durable, confirmed objective responses, 10 achieved target lesion shrinkage, and a further 22 achieved target lesion stabilisation. The most common grade 3 or 4 treatment-related adverse effects were fatigue (8%), diarrhoea (6%) and insomnia (6%). There was no sign of the liver and ocular toxicities seen with other HSP inhibitors.
HSP is molecular chaperone required for proper folding and activation of many cancer-promoting proteins, and is a key facilitator of cancer cell growth and survival, and there are many products in early-stage development that hit this target