Infinity Pharmaceuticals, Inc announced that, based on the recommendation of its independent data monitoring committee (IDMC), Infinity has elected to terminate the RING trial, a double-blind, placebo-controlled international phase-3 registration trial of IPI-504 (retaspimycin hydrochloride) in patients with refractory gastrointestinal stromal tumours (GIST).
The IDMC's recommendation yesterday evening to halt the trial was based on an early review of safety data from the first 46 patients enrolled in the study, which showed a higher than anticipated mortality rate among patients enrolled in the treatment arm. While the RING trial had similar entry criteria to the earlier study of IPI-504 in patients with refractory GIST, a preliminary review of the data suggests that the patients enrolled in the RING trial had more advanced disease, as evidenced by a greater percentage of patients having received three or more prior therapies and longer time since initial diagnosis. The company plans to fully analyze the data from this study in order to inform the ongoing development of IPI-504.
"Patient safety is our top priority and we have acted quickly to implement the recommendations of the IDMC," said Julian Adams, president of research and development and chief scientific officer. "While this outcome is disappointing, we would like to acknowledge the patients and caregivers who have participated in this trial and thank them for their support. We continue to believe in the therapeutic potential of Hsp90 inhibition, and are committed to the development of both IPI-504 and our oral Hsp90 inhibitor, IPI-493. We have now fully enrolled and look forward to sharing at ASCO data from our ongoing trial of IPI-504 in non-small cell lung cancer."
The RING trial will not enrol any new patients, and patients currently enrolled in the study will no longer receive IPI-504. Infinity is notifying all participating clinical trial sites and regulatory agencies of its decision.
Infinity plans to continue investigation of IPI-504, an inhibitor of heat shock protein 90 (Hsp90), in other cancers, including in the ongoing phase-2 portion of a trial in patients with non-small cell lung cancer, a phase-2 trial in combination with Herceptin (trastuzumab) in patients with HER2-positive metastatic breast cancer, and a phase-1b trial in combination with Taxotere (docetaxel) in patients with advanced solid tumours. Infinity, in collaboration with appropriate outside parties, will determine what changes, if any, may be needed or desired to maintain patient safety and optimize the development of IPI-504 in these and future studies.
"Despite the challenge that this news represents, it is important to put this information in the context of both our commitment to our Hsp90 inhibitor program and the overall strength of our pipeline and four-year financial runway," stated Steven H Holtzman, chair and chief executive officer of Infinity. "Infinity's financial strength is not affected by this development, and this financial strength will enable us to continue to invest in our deep pipeline of oncology drug candidates, as well as the continued development of IPI-504 in other cancers."
In addition to its Hsp90 programme, Infinity's pipeline includes its Hedgehog pathway inhibitor, IPI-926, currently in phase-1 clinical development, its fatty acid amid hydrolase (FAAH) inhibitor, IPI-940, for which IND-enabling studies are ongoing, and programmes in its discovery pipeline. Infinity is pursuing these programmes in collaboration with Mundipharma International Corporation Ltd and Purdue Pharmaceutical Products L.P.
Infinity anticipates announcing that it ended the first quarter of 2009 with approximately $153 million in cash, cash equivalents, and available-for-sale securities. The company also has access to a $50 million line of credit from Purdue Pharma. Infinity reiterates its financial guidance that it has capital to fund its current operating plan through at least the end of 2012. The company anticipates providing a more detailed update on its 2009 development plans and financial guidance during its conference call announcing first quarter 2009 results, which is planned for early May.
Infinity is an innovative cancer drug discovery and development company seeking to discover, develop, and deliver to patients best-in-class medicines for the treatment of cancer and related conditions.