FDA Clears Way for Trials of FOR46 in Late-stage Multiple Myeloma, Prostate Cancer

The U.S. Food and Drug Administration has allowed Fortis Therapeutics’ antibody-drug conjugate FOR46 to begin testing in a Phase 1 clinical trial as a therapy for late-stage multiple myeloma.

The trial (NCT03650491), scheduled to begin in early 2019, estimates to enroll 50 myeloma patients who have failed prior treatment regimens. Patients will first undergo a dose escalation phase to determine the maximum tolerated dose.

In a second stage, the selected dose will be tested for its safety, tolerability and anti-tumor activity. FOR46 will be administered intravenously every 21 days.

The study’s main goal is to determine whether the therapy is safe — measuring the number of adverse events and toxicities within one month after the last dose — and the proportion of patients who respond to FOR46.

A second Phase 1 trial (NCT03575819) will also test FOR46 for metastatic castration-resistant prostate cancer.

FOR46 is an antibody-drug conjugate directed against the CD46 protein, located at the surface of tumor cells in several cancers, including myeloma. CD46 is a negative regulator of the innate immune system, meaning that it can shut down the immune system’s response against tumor cells. Once bound to CD46-positive cells, FOR46 releases a toxic compound that causes cells to die.

Preclinical data by the team that developed FOR46 – led by Bin Liu at the University of California, San Francisco (UCSF) – showed that FOR46 inhibits proliferation in myeloma cell lines with little impact on normal cells. Moreover, FOR46 was powerful at eliminating myeloma tumor growth in mice.

“CD46 is an attractive target for a number of cancers but has yet to be exploited due to its role in healthy tissues,” Jay Lichter, PhD, president and CEO of Fortis Therapeutics, said in a press release.

“FOR46 cracks the code, in a sense, by binding a specific conformational epitope of CD46 that appears to be specific to tumor cells. This results in targeted tumor killing, while not impacting the natural role of CD46 in the complement system,” he said.

Marc Nasoff, PhD, chief scientific officer of Fortis, said: “It’s really a testament to the work of our scientists and the scientists at UCSF. By generating antibodies against tumor cells in situ, we developed a drug that readily translates to animal studies and, soon, human trials.

“We’re confident in the science and in our therapeutic, which builds upon decades of innovation and refinement of antibody-drug conjugates.”