The favorable study results have raised two issues: 1) the need to expand availability of Herceptin® while the FDA reviews Genentech's application, and 2) the need to expand clinical research with the drug. The National Cancer Institute (NCI) is working with Genentech to help make the drug available for testing in larger numbers of breast cancer patients and in more places around the country. NCI is also collaborating with Genentech to expand studies of Herceptin® for other indications and uses.

The purpose of this fact sheet is to describe NCI's role in this collaboration. More information about Genentech's work with Herceptin® and about the drug itself is available from the company at (650) 225-5759.

AVAILABILITY OF HERCEPTIN®

1. What is being done to increase supplies?

Current supplies of Herceptin® are quite limited. However, while awaiting FDA review, Genentech is increasing production of the drug and continuing to make it available through an "expanded access program." Under this program, which has been in effect for some time, patients who meet the Genentech eligibility criteria may enter a lottery to receive Herceptin®. Patients selected by lottery will become part of a non-randomized study. The lottery system was designed in consultation with breast cancer patient advocates, who consider a lottery the fairest way to make the currently limited supplies of the drug available.

2. What role will NCI play in expanding the availability of Herceptin®?

Initially, patients selected by the Genentech lottery were able to receive the drug as part of a study at about ten different hospitals. Now, the NCI is arranging to have the drug available in more locations through its Treatment Referral Center program. This program refers patients to receive experimental drugs at more than 50 NCI-designated cancer centers around the country. In the case of Herceptin®, some of these centers should be ready to accept eligible patients — those whose numbers are selected in the Genentech lottery — in mid-1998.

3. How can patients and physicians get more information?

Patients with advanced breast cancer who think they may be interested in entering HER2 trials, and their physicians, may call the NCI's Cancer Information Service (CIS) at 1-800-4-CANCER (1-800-422-6237). CIS information specialists will explain what steps a patient's physician should take to enter the patient in the Genentech lottery. Information specialists can also provide information on other trials.

NCI-SPONSORED STUDIES

4. What other studies of Herceptin® in breast cancer will NCI sponsor?

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 could start enrolling patients in mid-1998. These trials will be carried out by NCI's cooperative clinical trial groups and by investigators in other NCI-sponsored centers.

5. Is NCI supporting studies of Herceptin® to treat other cancers?

Yes. NCI and Genentech are already working together to study Herceptin® in tumors other than breast cancer. One current 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 lining cells of the abdomen). Both studies are being carried out through NCI-sponsored cooperative clinical trial groups. (These groups are networks of research centers around the country that conduct joint studies, using identical protocols and pooling their data.)

• Solid tumors: This is a phase I/pilot study of low-dose interleukin-2 plus Herceptin® in solid tumors — 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 one of the NCI cooperative trial groups, called the Cancer and Leukemia Group B (Protocol ID: CALGB-9661).

• Ovarian or peritoneal cancer: This is a Phase II study of Herceptin® in recurrent or refractory ovarian or primary peritoneal carcinoma. Phase II studies test the effectiveness of a drug in particular kinds of cancer. It is being conducted through the Gynecologic Oncology Group (Protocol ID: GOG-160).

6. Will NCI launch more studies of Herceptin® in other kinds of cancer?

Yes. Once there is an adequate drug supply, NCI and Genentech hope to explore the use of Herceptin® in a variety of malignancies, including gastric, endometrial, salivary gland, non-small cell lung, pancreatic, prostate, and colorectal cancers. 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®.

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

Yes. NCI currently 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 Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). You can also search the NCI's clinical trial database, called PDQ, on the Internet at http://cancernet.nci.nih.gov/prot/protsrch.shtml.

For more information about cancer visit NCI's Website for patients, public and the mass media at http://rex.nci.nih.gov or NCI's main website at http://www.nci.nih.gov.