Genentech Inc. and partners OSI Pharmaceuticals Inc. and Roche Holdings Inc. said a pivotal Phase III trial of Tarceva in advanced non-small-cell lung cancer demonstrated a 42.5 percent improvement in median survival and a 41 percent improvement in one-year survival rates compared to placebo.
Meanwhile, ImClone Systems Inc. and partners Bristol-Myers Squibb Co. and Merck KGaA said an international, randomized Phase III study of the colorectal cancer drug Erbitux met both its primary endpoint of locoregional control and its secondary endpoint of overall survival in treating head and neck cancer.
The firms released their respective favorable data over the weekend in New Orleans at the 40th annual meeting of the American Society of Clinical Oncology.
Outside the good news, ImClone, of New York, missed the survival endpoint in a study of IMC-BEC2, an investigational anti-idiotypic monoclonal antibody that mimics GD3 (a ganglioside), in small-cell lung carcinoma. Nevertheless, ImClone's stock (NASDAQ:IMCL) jumped 12.3 percent Monday, or $8.89, to close at $81.38. Genentech, on the other hand, which presented, or intends to present, 150 abstracts at the meeting, watched its stock (NYSE:DNA) fall $2.36 to close at $57.25.
The drop is despite the fact that the 731-patient Phase III trial (referred to as BR.21) of Tarceva hit its primary endpoint of improvement in overall survival and demonstrated significant effects in all secondary endpoints, including time to symptom deterioration, progression-free survival and response rate. OSI is expected to complete the rolling new drug application this summer using those data.
Tarceva (erlotinib HCl) is a small molecule designed to target the human epidermal growth factor receptor 1 (HER1) pathway, which is one of the factors critical to cell growth in many cancers. HER1, also known as EGFR, is a key component of the HER signaling pathway, which plays a role in the formation and growth of numerous cancers. The candidate is designed to inhibit the tyrosine kinase activity of the HER1 signaling pathway inside the cell, which may block tumor cell growth, the companies said.
The Phase III trial was a randomized, international, double-blind, controlled study comparing the use of 150 mg/day Tarceva vs. placebo for the treatment of patients with advanced NSCLC following failure of first- or second-line chemotherapy. The study randomized patients with a 2:1 ratio in favor of Tarceva, to receive either Tarceva or placebo.
Patients receiving Tarceva had a median survival of 6.7 months compared to 4.7 months in patients who received placebo (a 42.5 percent improvement). A hazard ratio of 0.72 and a "p" value of 0.001 were determined for comparisons of overall survival (a hazard ratio of less than one indicates a reduction in the risk of death and a "p" value of less than 0.05 indicates statistical significance).
In addition, 31 percent of patients receiving Tarceva in the study were alive at one year vs. 22 percent in the placebo arm (a 41 percent improvement). Statistically significant improvements in time to symptom deterioration were observed for key lung cancer symptoms of cough, pain and dyspnea, the partners said.
Genentech and OSI also are studying Tarceva with Avastin, Genentech's colorectal cancer drug, in renal-cell carcinoma and recurrent non-small-cell lung cancer.
At the conference, the partners released data from a 62-patient Phase II renal-cell carcinoma study in which the overall survival time after six months was 92 percent, and after one year, it was 81 percent.
Also, data from the 40-patient Phase I/II study in recurrent NSCLC demonstrated a median survival of 12.6 months, median progression-free survival of seven months and an estimated one-year survival rate of 54 percent.
Among its multiple abstracts, Genentech updated results from a Phase III study evaluating Herceptin (trastuzumab) in combination with paclitaxel and carboplatin, as well as a retrospective analysis of the pivotal Phase III Herceptin study, in women with HER2-positive metastatic breast cancer.
A trend toward improvement in overall survival was observed in patients receiving Herceptin/paclitaxel/carboplatin compared to those receiving Herceptin/paclitaxel - an increase to 36 months from 32 months. Additionally, at 48 months, 40 percent of patients who received Herceptin/paclitaxel/carboplatin were alive, compared to 31 percent of patients who received Herceptin/paclitaxel, Genentech said.
Meanwhile, Genentech, along with partners Biogen Idec Inc. and Roche, released positive data from a randomized Phase III trial evaluating Rituxan (rituximab), known as MabThera in Europe, in combination with chemotherapy as a front-line treatment for aggressive non-Hodgkin's lymphoma.
The trial enrolled 824 previously untreated patients in 18 countries, ages 18 to 60, with diffuse, large, B-cell NHL.
Investigators concluded that data from the MabThera International Trial demonstrated a significant improvement in time to treatment failure (TTF), the primary endpoint of the study. At two years, 81 percent of patients who received Rituxan and chemotherapy did not experience treatment failure, compared to 58 percent of patients who received chemotherapy alone. In the study, TTF was defined as documented progressive disease, failure to achieve a complete response rate, relapse or death, the companies said.
That trial, which was halted in December for reaching its pre-specified primary efficacy endpoint early, is the first randomized Phase III trial to evaluate whether Rituxan plus chemotherapy improves clinical outcomes in younger patients with aggressive NHL.
At two years, the investigators reported that overall survival was 95 percent (310/326) for those treated with Rituxan and chemotherapy compared to 85 percent (278/326) for patients who received chemotherapy alone.
ImClone To Discuss Data With Regulators
ImClone's Phase III trial (IMCL-9815) of Erbitux in head and neck cancer examined the impact of combining Erbitux with high-dose radiation on locoregional disease control and overall survival in 424 patients with advanced squamous-cell carcinoma of the oropharynx (area of the throat at the back of the mouth), larynx (voice box) or hypopharynx (cavity at the back of the mouth that opens into the esophagus) that has spread through the head and neck region.
Patients were randomized to receive radiation plus weekly Erbitux therapy (n=211) or radiation alone (n=213) for six to seven weeks.
According to the partners, the percentage of patients who achieved locoregional control at one year and at two years following treatment was 69 percent and 56 percent, respectively, in Erbitux-treated patients, compared to 59 percent and 48 percent for those treated with radiation alone. Likewise, the percentage of patients alive at two and three years post-treatment was 62 percent and 57 percent for the Erbitux-treated patients vs. 55 percent and 44 percent for those treated with radiation alone. Both the duration of locoregional control and the duration of survival were statistically significant (p=0.02 for both endpoints).
The companies plan to discuss those findings and other head and neck cancer clinical data with the FDA, as well as the European Medicines Agency.
In other business, ImClone said the IMC-BEC2 trial was designed to assess the survival benefit of vaccination with IMC-BEC2 and the immune stimulant BCG over a two-year period. Patients in the trial were randomized into either the treatment arm, receiving IMC-BEC2/BCG vaccination, or the observation arm.
The partners also released results of two clinical studies of Erbitux in combination with standard chemotherapy in the first-line treatment of advanced NSCLC and as a single agent in the treatment of patients with late-stage recurrent or metastatic NSCLC who have exhausted other treatment options.