OSI hopes to be in a position to file a Tarceva NDA in early 2004, when data in refractory non-small cell lung cancer patients is expected.

OSI and development partners Genentech and Roche announced Oct. 1 that a Phase III program for Tarceva (erlotinib) in combination with standard chemotherapy failed to show a survival benefit versus placebo.

Given the similar failure of another human epidermal growth factor receptor inhibitor, AstraZeneca's Iressa , to show a survival benefit as combination therapy, "we're not at all surprised with the data," OSI CEO Colin Goddard, PhD, told a same-day conference call.

The decision to conduct the combination studies was not based on positive preliminary data, but rather was a "logical business decision" because "a competitor was already running similar studies," Goddard said.

Both the 1,050-patient TRIBUTE study and the Roche-run ex-U.S. TALENT study of 1,200 patients failed to meet their primary endpoint of 25% improvement in survival rate. The TRIBUTE study did reach statistical significance for one of its secondary endpoints, time to symptomatic progression.

OSI now appears to be pinning its hopes for Tarceva in NSCLC on a Phase III trial for second- or third-line use as monotherapy. The 700-patient study is assessing 150 mg/day Tarceva with survival as the primary endpoint. Unlike the combination therapy trials, "this study design was based on very solid Phase II data," Goddard said.

AstraZeneca agreed to conduct a similar trial as a postmarketing commitment for Iressa, which gained accelerated approval in May ("The Pink Sheet" May 12, 2003, p. 3).

OSI now expects data from the monotherapy trial to be available in early 2004, slightly later than earlier predictions of late 2003. That could be an encouraging indication for Tarceva if the cause of the delay is increased survival time for trial subjects. "It's certainly not bad news," Goddard said, but "I think it would be worthy of caution before interpreting it as a positive."

Tarceva could have an advantage over Iressa if it is approved with survival data in refractory patients before AstraZeneca completes its Phase IV trial.

Genentech/OSI Tarceva NDA Filing Will Wait For Phase III Monotherapy Data

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