LEXINGTON, Mass. (
) --On May 3,
announced that an interim analysis of its ganetespib phase II trial in lung cancer was underway. Two months later, Synta still hasn't announced results. What is taking so damn long?
The painfully slow number crunching from the OPEN LABEL ganetespib study is even more mystifying given Synta already primed investors with good news. On May 3, the company also announced plans to push ganetespib into phase III studies based on the drug's "strong activity" in two subgroups of lung cancer patients enrolled in the phase II study. Synta didn't say which patient subgroups (prospectively defined, apparently) are benefiting from treatment but it's widely believed to be patients with mutation to the KRAS protein (mKRAS) and well as patients with high levels of the enzyme LDH. Both mKRAS and elevated LDH are negative markers of disease severity that makes treating lung cancer more difficult.
Not so coincidentally, Synta shares have doubled in value to more than $8 since May 3, as investors anticipate positive results from the ganetespib lung cancer study.
Any time now, Synta…
The Synta phase II study enrolls 240 patients with non-small cell lung cancer that no longer responds to initial therapy. The patients in the study are randomized to receive treatment with a combination of ganetespib plus the chemo drug docetaxel or docetaxel alone. The primary endpoint of the study is to determine whether adding ganetespib to docetaxel can significantly prolong the time before tumors start growing again or patients die -- so-called progression-free survival (PFS).
Synta has indicated that this interim analysis will encompass data from about half the patients in the study. The company has also hinted that the overall results are likely to be negative.
Why else discuss strong results and phase III plans in select patient subgroups if the drug is working more broadly?
How many of these subgroups of lung cancer patients were predefined, how many were positive and negative, and the size of each subgroup will be important questions for Snyta to answer when the trial results are reported.
Patients with lung cancer that contains high levels of mutant KRAS (mKRAS) are expected to benefit the most from ganetespib, with a doubling of PFS over docetaxel alone predicted by some analysts.
Investors will also use recently reported results from
phase II study of selumetinib in mKRAS lung cancer patients as a yardstick by which to measure ganetespib.
In the Array study presented at the recent ASCO meeting, selumetinib plus docetaxel resulted in a median PFS of 5.3 months compared to 2.1 months for docetaxel alone. Overall response rate was 37% for selumetinib plus docetaxel compared to no response for docetaxel alone. Both endpoints hit statistical significance; overall survival trended in favor of selumetinib (9.4 months vs. 5.2 months) but was not statistically significant. Again, mKRAS lung cancer patients were enrolled in this Array study, similar to those enrolled in the Synta study.
The toxicity profile of ganetespib will also be important. The drug is supposed to be formulated to avoid eye and liver toxicity that fouled clinical trials of older, similar cancer drugs known as heat-shock protein inhibitors.
Synta is also developing ganetespib as a treatment for the relatively small number of patients with lung cancer that expresses the ALK gene.
Xalcori is already approved as a therapy for these patients.
--Written by Adam Feuerstein in Boston.
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Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback;
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