Kosan Biosciences Incorporated announced the start of a Phase Ib clinical trial to evaluate KOS-862 (Epothilone D) in combination with Paraplatin (carboplatin) in cancer patients with advanced solid tumours. KOS-862 and Paraplatin will be administered in a dose-escalating study designed to establish the maximum tolerated dose, pharmacokinetics, safety, and potential clinical benefit of the two drugs given in combination.

The combination will be administered by intravenous infusion once a week for two out of every three weeks. Once the recommended Phase II doses are defined, additional patients will be treated to characterize the tolerability, pharmacokinetics, and potential clinical benefit of the drugs in combination, the release said.

"This is the second Kosan-initiated Phase Ib trial designed to evaluate KOS-862 in combination with standard chemotherapeutic agents. In addition to the Phase Ib trials currently being conducted with Gemzar (gemcitabine) and Paraplatin, the Kosan/Roche partnership is also evaluating KOS-862 in combination studies with Herceptin (Trastuzumab)," said Robert G Johnson, executive vice president, development and CMO, Kosan Biosciences.

KOS-862 is a polyketide that inhibits cancer cells by the same mechanism as paclitaxel, and in preclinical models was shown to be effective against paclitaxel-resistant tumours. Under a global development and commercialization agreement between Kosan and Roche, Roche has the worldwide exclusive right to market and sell KOS-862 and epothilone analogs owned by or licensed to Kosan for the treatment of cancer; Kosan will co-develop and has the right to co-promote Kosan/Roche epothilone products in the US for the treatment of cancer.

Kosan Biosciences has two first-in-class anticancer agents in Phase II clinical trials. KOS-862 (Epothilone D) is in Phase II and Phase Ib clinical trials and is partnered with Roche in a global development and commercialization agreement.

The results of preclinical studies evaluating KOS-862 and Paraplatin were presented at the AACR Annual Meeting in March 2004 in Orlando, FL. The studies concluded that the combination was synergistic in growth inhibition of human cancer cells in vitro and in an in vivo mouse xenograft model.