**3.3 LAG-3 inhibitor cancer therapy**

Britstol Myers Squibb [36]. Bristol Myers Squibb has formulated opdualag which consists of anti-LAG-3 mAb relatlimab with Opdivo (nivolumab) for the first-line

treatment for metastatic or unresectable melanoma [37]. It was previously reported that combination therapy of relatlimab and nivolumab increased PFS to 10.1 months compared with nivolumab monotherapy that shows PFS of 4.6 months only. Furthermore, 36% of patients treated with nivolumab monotherapy showed PFS of 12 months while in relatlimab combined with nivolumab, PFS was 47.7% [38]. In addition to this, Novartis has formulated a combination therapy targeting PD-1 and LAG-3, known as spartalizumab +LAG-525. It is now in a Phase II clinical trials to evaluate its role in unresectable or metastatic disease [39].

Tebolimab, manufactured by Macrogenic, is one of the first in class bispecific antibodies which is now undergoing Phase I clinical trials. This is composed of antigen binding fragments (Fab) targeting LAG-3 and PD-1. Pieris formulated PRS-332 which had two Fab regions targeting PD-1 and engineered lipocalins (anticalins) which was designed to target LAG-3. Similarly, F-star Therapeutics produced antibody FS118 that harbored a Fab targeting LAG-3 in its constant region and withPD-L1 targeting domains [34].

Although not all of these are approved yet, but various platforms that are offered to put more volumes in LAG-3-based cancer immunotherapy indicates that the pertinent checkpoint is clinically pivotal in cancers and hence an excellent target for therapy.
