QLT Inc. agreed to temporarily suspend enrollment in two Phase III studies of tariquidar in non-small-cell lung cancer patients on advice of a monitoring committee, which reportedly noted some toxicity in the study.
In a conference call with analysts and investors, and later in a telephone conversation with BioWorld Today, Paul Hastings, president and CEO of Vancouver, British Columbia-based QLT, was quick to point out that the roughly 300 patients already enrolled will continue to be dosed during the three-month suspension. Accrual thus far has reached the threshold number of patients required for the three-month interim analysis.
"The trials continue and when the interim analysis is done, the DSMC [Data and Safety Monitoring Committee] will make a recommendation to us of what to do, then we will listen to the recommendation and decide what we want to do. That will happen in May or June," Hastings told BioWorld Today.
Since enrollment is ahead of schedule, Hastings doesn't expect the suspension to set the pace back. In fact, he stands by the company's earlier expectation to file for U.S. regulatory approval in 2005 for use in combination with first-line chemotherapy in advanced non-small-cell lung cancer (NSCLC). "This just disrupts enrollment and it may not actually have a material impact on the timing of the trial, depending on how quickly we can reinitiate enrollment," he said.
Tariquidar is a P-glycoprotein (P-gP) membrane inhibitor that QLT licensed from Xenova Group plc, of Slough, UK, in August 2001. QLT owns rights in North America while Xenova retains them in Europe and the rest of the world. (See BioWorld Today, Aug. 15, 2001.)
QLT's stock (NASDAQ:QLTI) closed Friday at $8.74, down 43 cents, while Xenova's (NASDAQ:XNVA) suffered a major setback, closing at $4.52, down $1.78, or 28.3 percent.
Hastings has high hopes for tariquidar, saying P-gP inhibition is applicable across an array of solid tumors. P-gP is a membrane protein that pumps chemotherapeutic agents out of cancer cells.
In addition to the NSCLC indication, tariquidar also is the subject of a Phase II study in breast cancer.
The NSCLC Phase III studies making news Friday consist of two 500-patient, randomized, multicenter, placebo-controlled trials using tariquidar in combination with the two most commonly used chemotherapy regimens, paclitaxel plus carboplatin or vinorelbine alone. Enrollment began in June 2002 at about 100 sites in North America and Europe. The trials are designed to demonstrate the ability of tariquidar to enhance the efficacy of chemotherapy agents, and the primary endpoint is overall survival. (See BioWorld Today, July 1, 2002.)
But after about six months, the DSMC recommended the suspension so that all patients currently enrolled could be followed for a minimum of three months.
"The DSMC has made it clear that they do not want to disrupt the integrity of the trial and therefore unanimously recommended that it remain blinded," Hastings said in the conference call. "We think this is a good signal that there could be enough benefit in the trial to offset a higher level of toxicity."
The DSMC concluded that the recommended suspension "provided the best opportunity for these trials to remain intact and to serve, in their entirety, as pivotal registration trials for regulatory purposes," a prepared statement from QLT and Xenova said.
Hastings told conference call listeners that the DSMC has not seen any efficacy data and will not have such an opportunity until the currently treated patients have been followed up for at least three months and have been assessed by a CAT scan.
When asked by an analyst if the DSMC commented on specifics about adverse events possibly cropping up, Mohammad Azab, QLT's senior vice president and chief medical officer, said the committee had not released such details. However, he said, "We are reviewing the overall adverse events that occur without knowing which patients are treated by tariquidar and placebo. What we are seeing is the usual adverse events that we see with chemotherapy. We are not seeing anything out of the ordinary. However, we cannot determine the relative difference because we are blinded to the trial."
Regarding the Phase II breast cancer trial designed to enroll 30 patients, Hastings said patients and physicians will be informed of the NSCLC findings but the trial will not be halted.
The DSMC is an independent panel of experts whose primary responsibility is to oversee studies and safeguard the interests of current and future participants.