Shares of Telik Inc. (NASDAQ:TELK) fell 21 percent, or $1.22, to close at $4.59 on Monday after the company released the details of its three failed Phase III trials of Telcyta (canfosfamide HCl, TLK286).

Yet analyst Mark Monane of Needham and Co. LLC maintained his view that "Telcyta is an active compound, given the objective responses seen . . . to date." He added in a research note, however, that Telik faces "challenges in finding the right indication and the right trial design to show the benefit" of the drug.

Telik first announced that the ASSIST-1, -2 and -3 trials had not met their primary endpoints last December, sending the shares into a tailspin that ended in a 70 percent loss. Yet no actual data were provided at the time. Over the weekend, Telik presented data from the ASSIST-1 and -3 trials at the American Society of Clinical Oncology meeting in Chicago and revealed the ASSIST-2 findings in a news release. (See BioWorld Today, Dec. 27, 2006.)

ASSIST-1 was a 461-patient Phase III study comparing Telcyta as a monotherapy to either doxorubicin or topotecan in the third-line treatment of advanced, platinum refractory or resistant ovarian cancer. As previously announced, the trial did not achieve its primary endpoint of improving overall survival; in fact, the newly presented data showed that median survival was 8.5 months with Telcyta compared to 13.6 months in the control group (p=0.0001). The trial also missed its secondary endpoint of improving median progression-free survival, which was 2.3 months in the Telcyta group and 4.3 months in the active control group (p=0.0001).

Monane pointed out that the control groups "performed better than expected" in ASSIST 1, a fact Telik was at a loss to explain. Notably, Telcyta achieved one complete response and had a lower incidence of nausea, the most common side effect in both groups. ASSIST-2 also looked at Telcyta as a monotherapy, that time compared to Iressa (gefitinib, AstraZeneca plc) in the third-line treatment of non-small-cell lung cancer (NSCLC). As previously announced, the 530-patient Phase III study did not meet its primary endpoint of improving overall survival, which was 4.6 months in the Telcyta arm and 6.1 months in the control arm. The trial also missed its secondary endpoint of improving progression-free survival, which was 2.2 months in the Telcyta arm and 2.3 months in the control arm.

The ASSIST-3 trial returned to advanced, platinum refractory or resistant ovarian cancer, but that time evaluated a combination therapy regimen in a second-line setting. The 247-patient Phase III study compared the combination of Telcyta and carboplatin to doxorubicin alone. The trial missed its primary endpoint of improving response rate, a fact that Telik previously attributed to a major discordance between the clinical review of the tumor scans and the independent radiology review, which resulted in 25 percent of patients being prematurely discontinued from the trial prior to progression.

The new data confirmed what Telik already knew, and also revealed that median progression-free survival, the secondary endpoint, was 3.5 months for both groups. However, in a pre-specified analysis of 38 patients who had not received any treatments for six months or more prior to the trial, median progression-free survival in the control arm was still 3.5 months but had not been reached in the Telcyta arm (p=0.0099). In the subset, median survival was 11.1 months for the control group with a response rate of 10.5 percent compared to not yet reached for the Telcyta group with a response rate of 31.6 percent (p=0.0014).

The platinum refractory or resistant patient population in ASSIST-3 normally would not have been expected to respond to carboplatin alone, indicating that adding Telcyta may have enhanced the sensitivity to the chemotherapy. Telik is further exploring that in its ongoing ASSIST-5 trial, a Phase III study comparing Telcyta combined with doxorubicin to doxorubicin alone in the second-line treatment of platinum refractory or resistant ovarian cancer. To avoid the tumor-scan discrepancy problems in ASSIST-3, Telik changed the primary endpoint to a composite measure of progression-free survival that includes tumor response rate, CA-125 level and radiographic data.

Telik isn't throwing in the towel on lung cancer either. In April, data from a Phase II lung cancer trial combining Telcyta with carboplatin and paclitaxel in a first-line setting demonstrated a 34 percent response rate, with median progression-free survival of 4.9 months and overall median survival of 9.6 months. A Phase III lung cancer trial, dubbed ASSIST-4, should kick off next year. (See BioWorld Today, April 18, 2007.)

Telcyta is a cancer cell-activated chemo drug designed to exploit the overexpression of glutathione S-transferase P1-1 found in many cancer cells. Telik also is running a clinical program in myelodysplastic syndrome with Telintra (TLK199), a small molecule designed to stimulate blood cell production. The company reported $124 million in cash, cash equivalents and investments at March 31 and posted a net loss of $16.3 million for the quarter.