By Randall Osborne
ImClone Systems Inc. began a Phase III, 800-patient trial of BEC2, the company's cancer vaccine, to evaluate the drug in small-cell lung carcinoma.
"This is a survival study," said Samuel Waksal, president and CEO of New York-based ImClone.
"Patients, if they respond, usually have a major response, but they relapse quickly and go on to die," said Waksal, attending the American Society of Clinical Oncology (ASCO) conference in Los Angeles, at which the Phase III trial was disclosed.
"We're putting [patients] on chemotherapy and radiation, and if they respond, they get randomized into the trial," Waksal said.
The trial's endpoints are time to relapse and survival.
"Median survival time is only about six months," Waksal told BioWorld Today. "They do very badly, and we've already shown excellent data in pilot studies."
Enrollment at 70 centers is expected to take about two years, he said.
BEC2 is an anti-idiotypic monoclonal antibody that mimics the GD3 glycolipid expressed on certain tumors, designed to prevent them from growing in patients who have undergone reductive chemotherapy and radiation treatments.
The drug works by encouraging the immune system to recognize the tumors by way of the antigen. ImClone has been studying it to enhance immune responses in patients with small-cell lung cancer and malignant melanoma.
Last December, ImClone entered a $55 million co-marketing agreement with Merck KgaA, of Darmstadt, Germany, expanding their 1990 deal. Merck will pay for clinical development outside the U.S., and for development costs of the small-cell lung cancer trial worldwide. (See BioWorld Today, Dec. 5, 1997, p. 1.)
ImClone's stock (NASDAQ:IMCL) closed Tuesday at $10.75, down $0.875.
In other news from ASCO:
* Targeted Genetics Corp., of Seattle, reported Phase I results of its E1A gene therapy for treatment of breast and head and neck cancers. The data showed that among 16 of the 18 patients studied (nine with recurrent and unresectable breast cancer and nine with head and neck cancer), nine stabilized, two experienced a minor response despite having tumor progression at other untreated sites, and five got worse. E1A is a tumor inhibitor gene that stops tumor growth, suppresses metastases and reverses the overexpression of HER-2/neu, a cancer-causing gene. The company will initiate Phase II studies for E1A in head and neck cancer in the second half of this year.
* Ixsys Inc., of San Diego, said a Phase I trial of Vitaxin with 14 patients showed no significant toxicities. One patient, the company said, experienced greater than 50 percent regression of his tumor. Vitaxin is an antibody designed to inhibit angiogenesis, the formation of blood vessels necessary for tumor growth. Ixsys recently initiated a Phase I/II study at the University of Alabama to determine optimal dose. A Phase II trial is scheduled later this year.
* Cell Genesys Inc., of Foster City, Calif., said its T cell gene therapy produced a significant reduction in blood levels of TAG-72, a tumor-associated protein that is often elevated in colon cancer patients. In this trial, T cells are genetically modified to recognize TAG-72, which allows them to destroy colon cancer cells expressing the protein. Of the eight patients analyzed, six showed a greater than 80 percent reduction in circulating TAG-72 following infusion of T cell gene therapy.
* Introgen Therapeutics Inc., of Austin, Texas, said a Phase I/II trial of its INGN 201 (adenoviral-p53) gene therapy for patients with advanced non-small cell lung cancer showed the treatment was well tolerated and demonstrated evidence of clinical activity. Introgen is working with RPR Gencell, the gene therapy division of Rhone-Poulenc Rorer, of Collegeville, Pa. The gene therapy also appeared to have enhanced clinical activity in combination with the chemotherapeutic agent cisplatin. Fifty-two patients participated in the trial.
* Avax Technologies Inc., of Kansas City, Mo., said a study of M-Vax, its vaccine for Stage 4 malignant melanoma lung tumor, showed one of the 16 evaluable patients given the drug lived nearly three times longer than similar patients with Stage 4 melanoma. Three others are alive beyond the current average survival time. Avax began its Phase III of M-Vax for melanoma last fall. (See BioWorld Today, Oct. 31, 1997, p. 1.)
* Cell Genesys Inc., of Foster City, Calif., said an initial Phase I trial of GVAX gene therapy vaccine against prostate cancer showed an anti-tumor immune response. Preliminary results are similar to those from trials for kidney cancer and melanoma. Also, preliminary results from a follow-on Phase I/II trial of a second-generation GVAX product are encouraging, with enrollment of the projected 30 patients more than half complete.
* Cell Therapeutics Inc., of Seattle, reported no dose-limiting side effects in a Phase I trial of CT-2584, a small-molecule anti-angiogenic drug for chemotherapy-resistant cancers. Of 18 patients evaluable for tumor response, 18 remain alive at a median of eight months. Five experienced tumor stabilization. CT-2584 acts against tumor-cell phospholipids such as phosphatidic acid, believed to play a role in neoplastic cell transformation.
* Immunomedics Inc., of Morris Plains, N.J., reported on three studies of two cancer products. A radiolabeled antibody against carcinoembryonic antigen (CEA) was tested at escalating doses in patients with mestastatic and difficult-to-treat medullary thyroid cancer. Seven of 12 patients showed a decrease in their blood marker levels of calcitonin or CEA, measures of disease activity, and 11 of 12 patients with advanced disease showed stabilization for up to 26 months. In the second study, five of 12 advanced, chemotherapy-resistant non-Hodgkin's lymphoma patients receiving iodine-131-labeled LymphCide showed evidence of therapeutic effect, continuing at nine months. The third study, with the cancer imaging agent CEA-Scan, found the method useful in helping to determine the cancerous nature of women's breast lesions that are non-palpable but abnormal by mammography.
* Ligand Pharmaceuticals Inc., of San Diego, said its retinoic acid receptor-selective retinoid, LGD1550, was well-tolerated in Phase I/II clinical trials in advanced cancer. The company also reported favorable final Phase II data from a study of Panretin capsules (aliretinoin) in patients with AIDS-related Kaposi's sarcoma. (See BioWorld Today, Feb. 12, 1998, p. 1.)
* Medarex Inc., of Annandale, N.J., said continuing Phase II trials with its MDX-210 product showed quality-of-life improvements and prostate specific antigen (PSA) benefits in late-stage prostate cancer patients. MDX-210 is a bispecific antibody that targets the HER-2 receptor, and PSA is a biochemical marker associated with disease progression. Patients in both trials were treated first with granulocyte monocyte-colony stimulating factor, which increases certain white blood cells, and then with MDX-210, designed to trigger the killing function of immune cells. The drug also showed tumor reduction and disease stabilization in patients with kidney cancer who had failed all standard treatments.
* Sugen Inc., of Redwood City, Calif., presented data from a Phase II trial in glioma (brain cancer) of its lead product, SU101, a platelet-derived growth factor receptor inhibitor in Phase III trials for treatment of recurrent malignant glioma and in Phase II trials for prostate cancer. Of 15 end-stage patients, three achieved minor responses with a duration of 18 to 56 weeks (with one patient still on therapy) and three patients with stable disease with a duration of 16 to 26 weeks. Of adverse events, 92 percent were mild or moderate. The Phase II data provided the basis for the start of the Phase III trial, begun earlier this year.
* Titan Pharmaceuticals Inc., of South San Francisco, reported preliminary results in three Phase I/II clinical trials of its therapeutic cancer vaccines: TriAb, for breast cancer; CeaVac, for colon cancer; and TriGem, for melanoma and small-cell lung cancer. TriAb showed consistent immune responses in patients with mestastatic, as well as earlier stage, post-surgical breast cancer. In the CeaVac study, nine of 15 patients with resected colon cancer continued without evidence of disease, including four of eight patients with advanced cancer who continued beyond a year without recurrence. TriGem, a monoclonal antibody vaccine that mimics the GD2 antigen, caused all of 12 patients with mestastatic cancer to develop a GD2 tumor antigen specific immune response.
* U.S. Bioscience Inc., of West Conshohocken, Pa., said a Phase III trial of Ethyol (amifostine) showed the drug significantly reduced the incidence of chronic as well as acute xerostomia, or dry mouth, and associated symptoms in patients undergoing radiotherapy for treatment of head and neck cancer. *