Herceptin (Trastuzumab) is a monoclonal antibody, one of a group of drugs designed to attack specific cancer cells. Herceptin's targets are cancer cells that produce a protein called HER2 or HER2/neu, which occurs in high numbers in about 25 percent to 30 percent of women with metastatic breast cancer. The drug is made by Genentech Inc., in South San Francisco.

2. When did Herceptin become available? How is it obtained commercially?

The Food and Drug Administration approved Herceptin for marketing on Sept. 25, and Genentech began shipping the drug to physicians on Oct. 5. To obtain the drug, a physician places an order through a pharmaceutical wholesaler; the company then ships it overnight directly to the physician.

3. How does commercial availability affect NCI's expanded access trials with Herceptin?

Registration on NCI's two expanded access trials (TRC-9801 and TP-98-01) closed on Oct. 7 at 4:30 p.m. Patients already registered may continue to be treated and monitored on protocol for three months (until Jan. 7, 1999). After that, participants may continue on the protocol but will be required to pay for the drug.

4. How will participants obtain the drug after they leave the NCI trials?

Patients will be able to receive the drug through their own physicians. Assistance with patient reimbursement needs is available from Genentech's Single Point of Contact (SPOC) reimbursement service for health care professionals and consumers (1-888-249-4918). SPOC also manages the company's Patient Assistance Program which provides access for uninsured patients.

5. How many NCI-sponsored clinical studies with Herceptin are now in progress?

NCI is sponsoring four clinical trials with Herceptin. They include the two expanded access protocols -- TRC-9801 (NCI's original expanded access protocol) and TP-98-01. In addition, two trials of Herceptin in other tumors are under way (see question 10). Several other trials are in the planning stages.

6. What is TRC-9801?

This is a non-randomized study (all patients receive the drug) of Herceptin in patients with metastatic breast cancer who have received two prior chemotherapy treatments for metastatic breast cancer and now have progression of their disease. It is being coordinated through NCI's Treatment Referral Center, a mechanism through which patients can receive promising new drugs at NCI-designated cancer centers around the country before they become commercially available.

TRC-9801 was designed in conjunction with Genentech's expanded access program for Herceptin. Under this program, patients who met the study eligibility criteria had entered a lottery to receive Herceptin as participants in a study. The lottery ended Sept. 18, when more drug became available.

Initially, patients selected by the lottery received the drug as part of a study at about 10 different hospitals. Last spring, NCI arranged to have the drug available in more locations by opening TRC-9801. Eligible patients, selected through the lottery, could enroll in the study at any NCI-designated cancer center that had approved the protocol.

7. How was TRC-9801 expanded?

All patients who were enrolled in the lottery as of 4:30 p.m., on Friday, Sept. 18, who were not selected, and who still met the eligibility criteria for TRC 9801, could enroll in the trial. In addition, patients who were not entered in the lottery but who met the eligibility criteria for TRC-9801 could also enroll at a participating center. Registration closed on Oct. 7, 1998.

8. What cancer centers are participating?

Thirty-six cancer centers operating at 38 sites throughout the United States are participating in TRC-9801. A list of those centers is attached.

9. What is TP-98-01?

The new treatment protocol (TP-98-01) allows drug administration and follow-up by the patient's primary oncologist. Registration, now closed, was limited to patients who had been waiting for Herceptin for some time, having been enrolled in the lottery for the TRC-9801 protocol but not selected.

10. What are the other two Herceptin studies now being conducted by NCI?

One study is looking at the drug in a variety of solid tumors and another is assessing it in either ovarian cancer or cancer of the peritoneum (the cells lining the abdomen). Both studies are being carried out through NCI-sponsored cooperative clinical trial groups, which are networks of research centers that conduct joint studies and pool their data.

• Solid tumors: This is a phase I/pilot study of low-dose interleukin-2 plus Herceptin in solid tumors — i.e., most cancers with the exception of leukemias and lymphomas. Phase I studies involve a small number of patients, usually with advanced cancers, and test the safety of a new drug at various doses. This trial is being conducted through the Cancer and Leukemia Group B (Protocol ID: CLB-9661).
• Ovarian or peritoneal cancer: This is a Phase II study of Herceptin in recurrent or refractory ovarian or primary peritoneal carcinoma. As of Aug. 31, it was closed to accrual in order to assess initial data, but it could reopen. Phase II studies test the effectiveness of a drug in particular kinds of cancer. This study is being conducted through the Gynecologic Oncology Group (Protocol ID: GOG-160).

11. Will NCI conduct other studies of Herceptin in breast cancer?

Yes. NCI will be working with Genentech to study the use of Herceptin at different stages of breast cancer and in combination with other agents. These new breast cancer trials are still in the planning stage. They will be carried out by investigators in academic institutions and NCI-sponsored cooperative clinical trial groups, including cancer centers, and could start enrolling patients before 1999.

12. What about other kinds of cancer?

NCI and Genentech hope to explore the use of Herceptin in a variety of malignancies, including gastric, endometrial, salivary gland, lung, pancreatic, prostate, and colorectal cancers and osteosarcoma. Not all patients with these types of cancer have high levels of HER2. But as many as 30 percent to 40 percent of patients with some of these tumor types may overexpress the protein and therefore be candidates for clinical trials with Herceptin.

13. Is NCI supporting studies of other anti-HER2 antibodies?

Yes. NCI is involved in early trials of other monoclonal antibodies directed against the HER2 protein. For example, several phase I studies sponsored by NCI are testing a HER2 antibody, designated 520C9xH22, produced by the Medarex Corporation in Annandale, N.J. Other early, NCI-sponsored studies are evaluating a different HER2 antibody, 2B1, from Chiron Corporation in Emeryville, Calif.

Studies with other monoclonal antibodies targeted against different proteins on cancer cells are also under way. For more information, call the CIS at 1-800-4-CANCER (1-800-422-6237). The NCI's clinical trial database, called PDQ, can be reached on the Internet by going to http://cancertrials.nci.nih.gov.

For more information about cancer visit NCI's main Web site for clinical trials at http://cancertrials.nci.nih.gov.

Attached: Cancer Centers Participating in TRC-9801

Cancer Centers Participating in TRC9801: