ImClone Systems Inc. spent the weekend detailing its Erbitux trials at the American Society of Clinical Oncology meeting in Orlando, Fla., and generally worrying investors - the three trials provided mixed results, and ImClone's stock dipped as a result.
ImClone shares (NASDAQ:IMCL) fell $2.29 Monday, or 17.1 percent, to close at $11.12.
New York-based ImClone and its partner, Bristol-Myers Squibb Co., also of New York, said Saturday data were presented by investigators on an Erbitux Phase II trial in combination with cisplatin in treating refractory squamous-cell head and neck cancer. Nine of the 78 evaluable patients in the trial (11.5 percent) achieved a partial response and 13 patients (16.7 percent) achieved stable disease for an overall rate of disease control of 28.2 percent.
The companies on Sunday presented data from a study of Erbitux with docetaxel in patients with advanced non-small-cell lung cancer. The study enrolled 75 patients with advanced forms of the cancer who had progressive disease during, or disease recurrence within, three months of chemotherapy. Of the 30 evaluable patients, eight (26.7 percent) achieved a partial response and eight achieved a stable response. The overall rate of disease control was 53.4 percent.
Later Sunday, the companies said data from studies suggest Erbitux has antitumor activity as a single agent in chemotherapy-resistant colorectal cancer. Also, the drug has potential in combination with irinotecan, fluorouracil and leucovorin, the companies said.
In a 57-patient Phase II trial evaluating Erbitux as a single-agent treatment for refractory colorectal cancer, six patients (10.5 percent) achieved a partial response and 21 (36.8 percent) achieved stabilization of disease. The overall rate of disease control was 47 percent in the trial.
Erbitux, also known as cetuximab, or C225, is designed to target and block the epidermal growth factor receptor. Some observers said the trials were too small to be conclusive and that statistical significance was not achieved in certain instances, although there were signs of efficacy. Gruntal & Co. downgraded ImClone Monday from market outperformer to market performer.
In other news from the meeting:
Abgenix Inc., of Fremont, Calif., presented updated results from an ongoing Phase I trial of ABX-EGF, a fully human monoclonal antibody against the epidermal growth factor receptor. Co-developed by Abgenix and Immunex Corp., of Seattle, ABX-EGF was studied as a monotherapy in patients with various types of cancer. Data from the multiple-dose Phase I study of ABX-EGF included the results from 46 patients with various types of advanced refractory solid tumors, including kidney, prostate, pancreatic, non-small-cell lung, colorectal and esophageal cancer. Findings included that multiple doses of ABX-EGF appeared to be generally well tolerated at doses ranging up to 3.5 mg/kg, a partial response was achieved in a patient with colorectal cancer, a minor response was achieved in a patient with prostate cancer, and stable disease was achieved in two patients with non-small-cell lung cancer, one patient with colorectal cancer and one patient with gastro-esophageal cancer.
Allos Therapeutics Inc., of Westminister, Colo., presented updated survival results from a Phase II trial evaluating the use of RSR13 (efaproxiral) in patients with locally advanced, unresectable, non-small-cell lung cancer receiving thoracic radiation therapy following induction chemotherapy. The updated study, with a median follow-up of 22.9 months, showed median survival results of 20.6 months, a one-year survival rate of 67 percent and an estimated two-year survival rate of 35 percent. RSR13 is a synthetic small molecule that increases the release of oxygen from hemoglobin.
American Pharmaceutical Partners Inc., of Los Angeles, presented results of Phase II safety and efficacy trials of ABI-007, a protein-engineered nanoparticle form of paclitaxel. ABI-007 showed an 88 percent first-line response rate in metastatic breast cancer and 61 percent overall response rate. Also, ABI-007 showed activity in breast cancer patients who had progressed despite previous Taxol therapy. Scientists revealed ABI-007's mechanism of paclitaxel transport: It uses red blood cells as storage vehicles and increases tumor intracellular availability of paclitaxel. ABI-007 is cremophor-free and albumin-based.
Anosys Inc., of Menlo Park, Calif., said investigators reported the first trial results of dexosome therapy. Patients with advanced-stage non-small-cell lung cancer received Anosys' acellular anticancer dexosomes. The trial enrolled patients with unresectable Stage III and IV lung cancer who had previously been treated with up to three regimens. Also, the patients' cancers were positive for the expression of tumor antigens MAGE-3, -4 or -10. Three of seven immunized patients achieved prolonged disease stabilization.
Aphton Corp., of Miami, said investigators from the UCLA Jonnson Comprehensive Cancer Center in Los Angeles and the M.D. Anderson Cancer Center in Houston, presented interim results from a Phase II trial with previously untreated patients diagnosed with metastatic stomach cancer. The patients were treated with Aphton's antigastrin immunogen (G17DT) and chemotherapy consisting of cisplatin and 5FU. Of the 36 evaluable patients (20 percent more patients than previously reported), one patient had a complete response and 18 had a partial response for an overall response rate of 53 percent. Of the balance, 11 patients had stable disease, so that the combined tumor response rate and stable disease was 84 percent. Aphton's stock (NASDAQ:APHT) fell $1.68 Monday, or 15.7 percent, to close at $8.99.
AstraZeneca plc, of London, presented Phase II results from the pivotal ZD1839 (Iressa) IDEAL 2 study, reporting treatment data in patients with previously treated advanced non-small-cell lung cancer. Results from more than 100 symptomatic patients treated with Iressa show a reduction in tumor size in 12 percent of patients at a dose of 250 mg daily. Forty-three percent of patients experienced a reduction in lung cancer disease symptoms. The IDEAL 2 data presented are consistent with the IDEAL 1 interim data first presented in November, the company said.
Celgene Corp., of Warren, N.J., said data from a Phase II trial of its product, Thalomid (thalidomide), and Peapack, N.J.-based Pharmacia Corp.'s Camptosar (irinotecan), in metastatic colorectal cancer showed that, of the 20 evaluable patients, two patients experienced a complete response, four experienced a partial response and five had stable disease. Hematological side effects were the most significant adverse events reported in the trial. Based on the data, Celgene and Pharmacia initiated a Phase II/III study.
Cell Genesys Inc., of Foster City, Calif., reported long-term survival data from a Phase II multicenter trial of GVAX prostate cancer vaccine that demonstrated a dose-dependent trend toward prolonged survival in patients with hormone-refractory prostate cancer metastatic to bone. In the 34-patient study, seven of 10 patients receiving the higher dose level of the vaccine were alive 2.5 years after treatment (median survival: greater than 30 months). Of the 24 patients receiving the lower dose of the vaccine, nine of 22 patients (41 percent) were alive 2.5 years after treatment (median survival: 22 months), and two were lost during follow-up. Those results compare favorably to the reported median survival of seven to 11 months for hormone-refractory prostate cancer patients with bone metastases who are treated with chemotherapy, the current standard of care for this patient group, the company said.
Cell Pathways Inc., of Horsham, Pa., said Phase I data demonstrated the safety of Aptosyn in combination with carboplatin and docetaxel, carboplatin and paclitaxel, and with gemcitabine. Cell Pathways also presented the two-year use of Aptosyn (exisulind) in men with prostate cancer following radical prostatectomy. Results of the extension study show that Aptosyn treatment continued to increase prostate-specific antigen doubling time during a 24-month time period with manageable toxicity, in patients at high risk of prostate cancer recurrence. Aptosyn is a first-generation selective apoptotic antineoplastic drug.
Cell Therapeutics Inc., of Seattle, reported that Xyotax (polyglutamate paclitaxel, or CT-2103), a new-generation taxane, showed activity as a single agent in patients with recurrent ovarian cancer. The interim analysis of the Phase I/II study involving 88 patients indicated that Xyotax may offer clinical benefit compared to standard chemotherapies, with regard to efficacy, symptom control, safety and ease of administration. Antitumor responses were observed in all categories of chemotherapy sensitivity and resistance. The news apparently was not well received at the meeting, as the company's stock (NASDAQ:CTIC) fell $3.21 Monday, or 26 percent, to close at $9.14.
Eli Lilly and Co., of Indianapolis, said preliminary research findings suggest that a combination of Gemzar (gemcitabine) and Alimta (pemetrexed) is active in the treatment of pancreatic cancer. In a Phase II study, the Gemzar-Alimta combination had a one-year survival rate of 32 percent, which has prompted the initiation of a Phase III study comparing Gemzar-Alimta to Gemzar alone. Gemzar is approved by the FDA for the treatment of patients with pancreatic cancer. Alimta is a multitargeted antifolate. The study involved 42 patients in the U.S. with previously untreated advanced pancreatic cancer. The data included an objective response rate of 12 percent, a 13 percent clinical benefit response rate, and a median survival time of 6.6 months.
EntreMed Inc., of Rockville, Md., reported evidence that Panzem demonstrated anticancer activity with disease stabilization and declining prostate-specific antigen levels in some hormone-refractory prostate cancer patients who participated in a Phase II trial. Clinical investigators also reported that Panzem, taken orally, was safe and well tolerated and demonstrated signs of inhibiting blood vessel growth. Separately, the company released Phase I data showing Angiostatin, when combined with radiation therapy, was safe with no dose-limiting toxicity in patients with cancers that require radiation therapy. Tumor responses were demonstrated in 90 percent of patients who entered the trial with measurable disease in the radiation field. Also, no clinically significant side effects were reported.
Genentech Inc., of South San Francisco, had its product, Herceptin, as the focus of a study done by the University of Miami Sylvester Comprehensive Cancer Center that found Herceptin, in combination with the chemotherapy drugs Taxotere (docetaxel) and cisplatin, shrank breast tumors in one out of four women who participated in the study, making locally invasive cancers undetectable. Half the women were node-negative by the time of surgery. Herceptin is a monoclonal antibody developed against the HER-2/neu protein.
Genaera Corp., of Plymouth Meeting, Pa., reported results of its anti-angiogenic drug, squalamine, in a Phase II recurrent advanced ovarian cancer clinical trial. In the study, 35 percent of evaluable patients (nine of 26) had an objective response to the regimen of squalamine and carboplatin, including five complete responses and four partial responses. Separately, the company reported positive final results for squalamine in a Phase IIa non-small-cell lung cancer trial examining squalamine, combined with first-line standard chemotherapy of carboplatin and paclitaxel, in patients with Stage IIIb or Stage IV advanced disease. For all patients enrolled in the study, at all doses of squalamine, 27 percent of patients experienced an objective response.
Genitope Corp., of Redwood City, Calif., said results from a Phase II trial of its GTOP-99 personalized immunotherapy in patients with advanced-stage follicular non-Hodgkin's lymphoma (f-NHL) who had not previously received chemotherapy for their disease demonstrated that a personalized immunotherapy, when used as the initial treatment for patients with f-NHL, can induce tumor-specific antibody and T-cell immune responses. The study involved 16 patients. A Phase III trial is being conducted at 25 institutions in the U.S. and Canada.
GenVec Inc., of Gaithersburg, Md., presented Phase Ib trial data for TNFerade. The studies were conducted at four centers around the country and involved patients with a variety of cancers, including cancer of the breast, lung, head and neck, skin, rectum and pancreas. TNFerade showed substantial activity against all types of tumors tested, the company said. The data included 15 of 21 patients showing objective tumor shrinkage and five of 21 showing stable disease. TNFerade delivers the human tumor necrosis factor-alpha gene to tumors, using GenVec's adenovector gene delivery technology.
Human Genome Sciences Inc., of Rockville, Md., presented some of the preclinical data that supported the filing of its investigational new drug application to the FDA for LymphoRad 131 for use in the treatment of B-cell cancers. On May 14, Human Genome announced that LymphoRad was cleared by the FDA for Phase I studies. The first trial will be done in patients with multiple myeloma. Preclinical studies suggest that LymphoRad, a radioiodinated form of B-lymphocyte stimulator, binds to receptors found only on B cells and B-cell tumors, delivering low doses of radiation.
ImmunoGen Inc., of Cambridge, Mass., and British Biotech plc, of Oxford, UK, presented safety and pharmacokinetic data from the first human trial of the Tumor-Activated Prodrug product, huN901-DM1/BB-10901. BB-10901 is a conjugate of the cytotoxic maytansinoid drug, DM1, with the humanized monoclonal antibody, huN901. The ongoing Phase I study in patients with advanced small-cell lung cancer and other solid tumors potentially targeted by the drug is designed to evaluate the pharmacokinetics and maximum tolerated dose of BB- 10901 when administered as a single infusion once a week. To date, 23 patients have been enrolled in the study. The drug has been well tolerated with no dose-limiting toxicity found. At the 60 mg/m2 dosage level, two patients experienced dose-limiting events, but it was unclear if they were drug-related. Pharmacokinetic analysis found the agent to have a half-life of approximately one day at the 40 mg/m2 dose level. One patient had a transient partial response (greater than 50 percent tumor reduction) at the 40 mg/m2 dosage level. Another patient had a minor response (greater than 35 percent tumor reduction) at the 60 mg/m2 dosage level. Two additional patients had disease stabilization.
Isis Pharmaceuticals Inc., of Carlsbad, Calif., and Eli Lilly and Co., of Indianapolis, said Affinitac, an investigational targeted therapy used in combination with chemotherapy, demonstrated high rates of tumor response and stable disease in the treatment of non-small-cell lung cancer (NSCLC), according to results from separate ongoing Phase II trials. Affinitac (formerly LY900003) is being developed for the treatment of NSCLC through an alliance between the companies. The antisense agent targets protein kinase c-alpha. The first presentation involved results from a study in which Affinitac is being evaluated in combination with Gemzar (gemcitabine) and cisplatin in previously untreated patients with advanced NSCLC. The second presentation involved results from a study in which Affinitac is being studied in combination with docetaxel in previously treated NSCLC patients.
Maxim Pharmaceuticals Inc., of San Diego, reported results of Ceplene studies in combination with interleukin-2 for the treatment of advanced metastatic melanoma. The results included additional analyses of Maxim's controlled 305-patient Phase III trial. The analyses suggested that the combination provided a statistically significant survival benefit for the most critically ill patients. After 24 months of follow-up, 17 percent of the patients receiving Ceplene and interleukin-2 were alive, compared to 8 percent of patients receiving interleukin-2 alone.
MGI Pharma Inc., of Minneapolis, presented data supporting the development of irofulven in a variety of cancers as both a monotherapy and in combination therapy. Irofulven is MGI's compound that displays antitumor activity and retains cytotoxic activity in tumors with different types of drug-resistance mechanisms, the company said. Also, MGI and its partner, Switzerland-based Helsinn Healthcare SA, presented Phase II results demonstrating the potential efficacy of palonosetron in the prevention of acute chemotherapy-induced nausea and vomiting in patients who received highly emetogenic chemotherapy. The study results showed palonosetron was effective in the prevention of nausea and vomiting during the initial 24-hour period and for several days beyond. Palonosetron is a 5-HT3-receptor antagonist with an extended half-life and a receptor-binding affinity.
Millennium Pharmaceuticals Inc., of Cambridge, Mass., reported updated preliminary findings of its Phase II trial of MLN341 (formerly known as LDP-341 and PS-341) in patients with multiple myeloma whose disease has relapsed and not responded following multiple prior treatments. The study showed that MLN341 stabilized or reduced myeloma protein in the majority of study participants. Also, the majority of patients did not experience disease progression during the 24-week study, the company said.
NeoRx Corp., of Seattle, presented results from a Phase I study of Pretarget Lymphoma, a targeted therapeutic in development for patients with non-Hodgkin's lymphoma. The Phase I data indicated that Pretarget Lymphoma was usually well tolerated, and may provide a means to deliver higher doses of radiotherapeutic to tumor cells. Fifteen patients with relapsed or refractory CD20-positive adult B-cell NHL participated in the study. Data were presented for the 11 evaluable patients to date.
Novartis AG, of Basel, Switzerland, and its unit, Novartis Oncology, said new data demonstrated that more than 60 percent of patients with an inoperable form of gastrointestinal cancer are continuing to respond to Gleevec (imatinib mesylate) after one year of follow-up. Gleevec was approved by the FDA in February for the treatment of patients with Kit (CD 117)-positive unresectable and/or metastatic malignant gastrointestinal cancers. In the randomized Phase II study, with a median follow-up of 15 months, the overall rate of confirmed partial response was greater than 60 percent, based on Southwest Oncology Group criteria. At the 15-month follow-up, approximately 70 percent had not progressed, discontinued treatment or died. More than 60 percent of patients had tumors that shrank by at least half. Results did not differ substantially between the two dosages.
Progenics Pharmaceuticals Inc., of Tarrytown, N.Y., and Cytogen Corp., of Princeton, N.J., through their joint venture, PSMA Development Co. LLC, selected a fully human monoclonal antibody that targets prostate-specific membrane antigen (PSMA) for development as a therapy for prostate cancer. The antibody was produced under a collaboration with Abgenix Inc., of Fremont, Calif., using its XenoMouse technology. In the coming months, the PSMA Development Co. expects to begin Phase I/II studies of a therapeutic prostate cancer vaccine comprising recombinant PSMA protein and an adjuvant.
SuperGen Inc., of Dublin, Calif., updated data from an ongoing study of its oral anticancer compound, Orathecin, in patients previously treated for advanced gastric adenocarcinoma. The Phase II trial is taking place at the M.D. Anderson Cancer Center in Houston. Thirty-three patients previously treated with no more than one regimen of chemotherapy and with either locally advanced unresectable or metastatic gastric cancer were evaluable. Among them, there was a 12 percent response rate (one complete response and three partial responses), and 33 percent experienced disease stabilization. Nineteen of the 33 patients in the study are still alive. The overall clinical benefit was 45 percent, SuperGen said.
Telik Inc., of South San Francisco, presented preliminary results of a Phase II trial of TLK286 in patients with advanced, platinum-resistant, non-small-cell lung cancer. TLK286 had single-agent antitumor activity in patients with highly resistant disease. Separately, the company presented preliminary results of the Phase II trial of TLK286 in patients with advanced ovarian cancer. TLK286 showed significant single-agent antitumor activity in the patient group. Telik also presented final results from the Phase I dose-escalation trial of TLK286, administered using a weekly dosing schedule. TLK286 was well tolerated in the trial and showed additional evidence of clinical benefit in several cancer types. TLK286 is a small-molecule antitumor drug that is activated by GST P1-1. Telik's stock (NASDAQ:TELK) rose $1.14 Monday, or 10.2 percent, to close at $12.36.
Therion Biologics Corp., of Cambridge, Mass., said its Prostvac vaccines, vaccinia and fowlpox, were used in a prime-boost protocol in stage D0 prostate cancer patients who have rising PSA levels but no evidence of metstases. At 24 months post-treatment, 53 percent of patients treated with varying sequential vaccinations of Prostvac remained stable for six months or more. Also, 78 percent of patients who received the Therion vaccines remained free of metastatic prostate cancer. The Phase II trial was a randomized, multicenter study.
Titan Pharmaceuticals Inc., of South San Francisco, reported that Pivanex demonstrated clinical benefit and showed promise for treatment of refractory non-small-cell lung cancer in a Phase II study. Results with Pivanex were shown to be encouraging in patients whose cancer had progressed after one or two prior chemotherapy regimens. Additionally, Pivanex was not associated with any significant side effects in the study. Pivanex acts by inhibiting enzymes called histone deacetylases, which are responsible for changing the expression of cancer-related genes.
Tularik Inc., of South San Francisco, presented posters and abstracts on its anticancer drugs, T67 and T607. In a Phase II unresectable hepatocellular carcinoma study of T67, three of 34 patients had partial responses and 38 percent (13 of 34) had stable disease. Also, five of 27 evaluable patients had a more than 50 percent reduction in alpha-fetoprotein. T67 binds to B-tubulin, which is essential to cell division. T607 is an analogue of T67, although it does not cross the blood-brain barrier and has a different tissue distribution profile.
Vical Inc., of San Diego, presented an update on Allovectin-7 cancer vaccine program. Its high-dose Phase II trial had recruited 67 patients as of May 3; Vical aims to enroll up to 80 patients. Interim results from Vical's Phase II registration trial show, based on the most recent database update, an estimated median survival for all 78 patients treated of 14.3 months. Of the eight patients who investigators previously reported as responders (unaudited), seven were still alive at the time of the most recent update.
XOMA Ltd., of Berkeley, Calif., said Results of a Phase I study of Human Engineered ING-1 (heMAb) monoclonal antibody in patients with solid tumors showed positive safety and tolerability results. Additional data suggest that the Human Engineering methodology yields therapeutic antibodies with minimal immunogenicity in humans, comparable to antibody humanization methods. The study was designed to evaluate intravenously administered ING-1 in patients with advanced adenocarcinomas of the breast, gastrointestinal tract, lung, ovary and prostate that are refractory to standard therapies.