A Phase 1 trial testing FS118 – F-star‘s antibody designed to target two immune checkpoint proteins – in solid and advanced cancers has dosed a first patient, the company announced.
The U.S.-based study (NCT03440437) is expected to enroll 51 patients with advanced or metastatic cancers who have not responded to prior treatment with PD-1/PD-L1 inhibitors. Researchers will evaluate the safety, tolerability, stability, and therapeutic activity of ascending FS118 doses, with the ultimate goal of identifying the optimal dose to use in further testing.
Patients will receive weekly intravenous injections of FS118 in three-week treatment cycles until signs of toxicity or disease progression are detected.
“The initiation of a Phase 1 clinical study of FS118 is a pivotal milestone for F-star and validation of our unique bispecific technology and approach to improving cancer care” John Haurum, CEO of F-star, said in a press release. ”FS118 leverages novel biology that cannot be attained through combination approaches, we believe this is an important step forward in providing improved therapies for patients with advanced cancer.”
FS118 is an antibody that simultaneously inhibits the LAG-3 and PD-L1 molecules. These are immune checkpoint molecules produced by tumors to prevent immune surveillance.
Inhibitors of the PD-1 and PD-L1 molecules have been showing promise in multiple cancers, but many patients still fail to respond to them or see their disease return after a while. Researchers believe this resistance may be caused by the expression of LAG-3 on certain immune T-cells.
This suggests that treating patients with antibodies against PD-1 and LAG-3 could improve outcomes, including patients who relapsed or are refractory to PD-1/PD-L1 inhibitors.
F-star developed what is called a bispecific antibody, one that targets both molecules at the same time.
In mice, FS118 was better at activating anti-cancer T-cells than a PD-L1 inhibitor alone and induced tumor responses that were similar to a combination of anti-LAG-3 and anti-PD-L1 antibodies.
These results, recently presented at the 2018 American Association of Cancer Research (AACR) Annual Meeting, in Chicago, supported the initiation of the Phase 1 trial.
The presentation was titled, “Dual blockade of PD-L1 and LAG-3 with FS118, a unique bispecific antibody, induces CD8+ T-cell activation and modulates the tumor microenvironment to promote antitumor immune responses.”
“FS118 is positioned to address a clear unmet medical need as only approximately one in five patients treated with checkpoint inhibition monotherapy reach durable and clinically meaningful responses,” said Neil Brewis, CSO of F-star. “FS118 has the potential to increase this response rate by overcoming tumour resistance and restoring anti-cancer immunity and responsiveness.”
This investigative antibody is one of several under option to Merck KGaA (known as EMD Serono in the U.S. and Canada) as part of a collaboration agreement announced in June 2017. After disclosure of pre-established data, the company may opt to acquire FS118, gaining full rights for its development and commercialization.