Pfizer/Coley Prep Phase III Study Of ProMune For First-Line Lung Cancer

ProMune Phase III lung cancer trial plans outlined in Coley's recent IPO prospectus filing. With licensee Pfizer funding ProMune for cancer applications, the bulk of the initial public offering proceeds will go toward expanding Coley's early-phase infectious disease program.

Pfizer and Coley will seek an indication for first-line treatment of advanced non-small cell lung cancer for their toll-like receptor agonist ProMune (CPG 7909).

Based on a survival benefit in a Phase II trial and discussions with FDA, "we expect that Pfizer will initiate a pivotal Phase III clinical trial," Coley says in a recent filing with the Securities & Exchange Commission for an initial public offering.

A proposed Phase III trial design was submitted to the agency at an end-of-Phase II meeting Sept. 1, 2004. Coley and licensee Pfizer will also seek a special protocol assessment "in 2005," according to Coley.

"In our randomized Phase II clinical trial of ProMune in combination with chemotherapy for first-line treatment of [NSCLC], which included both of the major histologic subtypes of NSCLC, we observed a statistically significant improvement in overall response and a potentially meaningful survival benefit in patients receiving ProMune," Coley reported.

The 112-patient, randomized Phase II trial of the toll-like receptor 9 (TLR9) agonist ProMune in combination with standard two-drug chemotherapy in first-line advanced NSCLC (stages IIIb and IV) showed a 71% improvement in median overall survival compared to chemotherapy alone (11.7 months vs. 6.8 months; p=0.185).

Compared to chemotherapy alone, ProMune yielded a 31% improvement in one-year survival (47% vs. 36%; p=0.191) and a 95% increase in overall response rate (37% vs. 19%; p=0.048).

"Although the Phase II clinical trial was not powered to demonstrate statistical significance, we believe that the observation of a statistically significant difference in overall response rate, the primary endpoint of the study, and the observed clinically meaningful benefit in patient survival, support our conclusion that a pivotal Phase III clinical trial is warranted," Coley said.

Coley is also highlighting safety benefits with ProMune, including "fewer side effects." As ProMune works with anti-tumor immune responses, the drug has "a favorable safety profile when compared to many existing therapies." The Phase II data were presented May 14 at the American Society for Clinical Oncology meeting in Orlando, Fla.

If the Phase III trial can confirm a survival benefit for front-line treatment of lung cancer in a broad patient population, the firms would achieve a goal that has proved elusive for competitors.

Most notably, AstraZeneca's epidermal growth factor receptor inhibitor Iressa (gefitinib) and Genentech/OSI's EGFR inhibitor Tarceva (erlotinib) have failed to show an overall survival benefit in first-line NSCLC. Ligand reported in March that two pivotal Phase III trials of Targretin (bexarotene) for front-line NSCLC in combination with chemotherapy failed to show a survival benefit.

A Phase III trial of Bristol-Myers Squibb/ImClone's EGFR agent Erbitux (cetuximab) for first-line NSCLC treatment in conjunction with chemotherapy is ongoing.

An interim Phase III analysis of Genentech's vascular endothelial growth factor inhibitor Avastin (bevacizumab) has shown a 22.5% improvement in overall survival in first-line NSCLC patients with adenocarcinoma who were not at high risk of pulmonary bleeding.

The Avastin results "represent the first study combining a targeted biologic therapy with chemotherapy to show an overall survival improvement in the first-line [NSCLC] setting, and the first time that any treatment has improved upon the standard, two-drug chemotherapy regimen in this disease," Genentech Senior VP-Development Hal Barron said March 14.

"While the Avastin data represented a significant improvement, that trial enrolled only a subset of the NSCLC patient population, excluding those with squamous cell carcinomas and certain cardiovascular diseases," Coley noted. "Accordingly, we believe there remains room for further improvement in the treatment of this patient population."

Wellesley, Mass.-based Coley is seeking to raise up to $115 mil. in its initial public offering. With Pfizer funding ProMune for cancer applications, the bulk of the IPO proceeds will go toward expansion of Coley's early-phase infectious disease program, including ongoing Phase Ib trials of Actilon (CPG 10101) for hepatitis C.

Pfizer will buy up to $10 mil. in Coley stock in conjunction with the IPO under the firms' March 24 license deal. Pfizer also has paid Coley $50 mil. up-front and will provide up to $455 mil. in milestone payments, plus royalties. Receipt of the $50 mil. payment was announced by Coley May 16, following Hart-Scott-Rodino antitrust clearance.

- Jon Dobson