Trodelvy Falls Short As NSCLC Treatment, Taking Some of the Shine Off Antibody-Drug Conjugates

Antibody-drug conjugates have been a hot ticket in oncology lately. Johnson & Johnson announced earlier this month that it had purchased Ambrx, a California company developing the antibody-drug conjugates, for $2 billion. Merck announced in October 2023 that had signed a deal worth up to $22 billion with Daiichi Sankyo to commercialize three antibody-conjugate. Earlier in the year, Pfizer announced that it was shelling out $43 billion to buy Seagen, a Washington state company developing antibody-drug conjugates.

Some bloom came off the category today when Gilead announced that its antibody-drug conjugate, Trodelvy (sactituzumab-govitecan) had failed to meet its primary endpoint in a phase 3 testing the drug as a treatment for metastatic non-small cell lung cancer.

Gilead’s (Nasdaq: GILD) stock price fell 10% today following the early morning announcement.

Antibody-drug conjugates are combination drugs that consist of a monoclonal antibody that “finds” the cancer and a drug that kills the cancer cell. Hitching the cytoxic agent to the monoclonal antibody makes the killing action of the cytoxic agent more precise.

Trodelvy (pronounced troh-DELL-vee) has been on the market as a treatment for other cancers for several years. The FDA approved it on an accelerated basis in 2020 for triple-negative breast cancer, a relatively rare and aggressive form of breast cancer. In 2021, the drug regulator approved it as a treatment for bladder cancer. In February 2023, the FDA approved Trodelvy for previously treated HR-positive, HER2-negative breast cancer. HR-positive, HER2-negative breast cancer is among the most common types of breast cancer, so that approval has been characterized in media reports as crucial to the drug’s commercial success.

The findings announced in today’s news release were from the EVOKE-01 trial, a phase 3 trial comparing treatment with Trodelvy to docetaxel, a taxane that is used to treat several types of cancer. Gilead said in the release that a three-month difference in median overall survival was seen in a subgroup of patients who were nonresponsive to the last prior anti-PD-(L)1 therapy, a class of drugs that includes Tecentriq (atezolizumab) and Imfinzi (durvalumab) but that subgroup analysis was not designed for formal statistical testing.