Threshold Pharmaceuticals’ TH-302 combination phase IIb study for pancreatic cancer has reached its primary endpoint with a 63% improvement in progression free survival and a safety profile consistent with previous studies.

The multi-center, 214-patient trial evaluated the efficacy and safety of two doses of the investigational agent TH-302 in combination with gemcitabine compared to gemcitabine alone in patients with first-line advanced pancreatic cancer.

Patients were randomized equally into one of three cohorts: TH-302 at a dose of 240 mg/m2 plus gemcitabine, TH-302 at a dose of 340 mg/m2 plus gemcitabine, and gemcitabine alone. Patients who successfully completed six cycles of treatment without evidence of significant treatment-related toxicity or progressive disease could continue to receive treatment.

The median progression-free survival (PFS) was 5.6 months for patients treated with gemcitabine in combination with TH-302 at 240 mg/m2 and 340 mg/m2 compared to 3.6 months for patients treated with gemcitabine alone. The PFS hazard ratio comparing the TH-302 combination to gemcitabine alone was 0.61 (95% confidence interval: 0.43 - 0.87) which was highly statistically significant (p = 0.005). The response rate in the combination arms was 22% compared to 12% in the gemcitabine alone group. Results also demonstrated greater efficacy in the higher TH-302 dose group compared to the lower dose group.

The combination was well tolerated with a safety profile that was consistent with Threshold’s prior study of this combination regimen. As in that study, skin and mucosal toxicities related to TH-302 were dose dependent, but not dose limiting.

"This study provides the proof of concept demonstration that TH-302 contributes to the efficacy of a known active agent and supports the rationale for combining TH-302, a hypoxia targeting agent, with other approved therapies," said Stew Kroll, senior vice president of biostatistics and clinical operations of Threshold.

Threshold said more detailed results of the trial will be presented at a future major medical conference.