# FDA Approvals of Biologics in 2022
## 4 Therapeutic Indications and Mechanisms of Action
### Cancer
This ADC is a FR\(\alpha\)-directed (folate receptor alfa) chimeric mAb that targets epithelial ovarian cancer, which has high expression of FR\(\alpha\). When internalized, ElahereTM releases its small molecule (DM4), a microtubule inhibitor, after cleavage of its disulfide linker, unleashing apoptotic cell death. The anti-tubulin agent DM4 is an analog of maytansine, which was last found, before 2022, almost one decade ago in another ADC KadylaTM (rastuzumab emtansine) [30]. DM4 is genotoxic, it confers risk to pregnant women, and it is a potent CYP3A4 substrate. Patients treated with DM4 must be closely monitored [25]. From 2015 to 2021, nine ADCs were approved by the FDA [1] and ElahereTM is the tenth of this class. Regarding efficacy, in a single-arm trial, ElahereTM demonstrated an ORR of 31.7% and a DOR of 6.9 months, but further research is still ongoing [40; 41]. Ongoing Clinical Trials for the New Biologics for Cancer  
There are trials ongoing for tebentafusp (phase 1b/2) to test this Biologic in metastatic cutaneous melanoma, but in combination with other Biologics (durvalumab and/or tremelimumab), and also tebentafusp alone in advanced non-uveal melanoma, with no results posted yet [42]. Regarding trials for nivolumab and relatlimab to potentially treat diseases other than its primary target, there are trials ongoing to test it in metastatic or unresectable chordoma and [43], a phase 2 trial to test it in advanced microsatellite stable (MSS) colorectal cancer [44], a phase \(\frac{1}{2}\) trial to test its effectiveness in liver cancer [45], and interestingly, just like KimmtrakTM (tebentafusp) mentioned earlier in this paper, whose therapeutic indication is metastatic uveal melanoma (MUM), the first treatment to date specifically for MUM, there is a phase 2 trial ongoing to test nivolumab and relatlimab for MUM [46]. A combination of mAbs such as OpdualagTM carries great potential for repurposing and exploiting new targets/diseases; unfortunately, there are no results posted yet regarding the ongoing trials mentioned. Tremelimumab is being tested for bladder cancer, with a completion study date in 2026 [47]. It is currently only approved for adult patients, but ongoing studies were found to test tremelimumab in combination with durvalumab in pediatric patients with solid tumors and hematological malignancies [48], and a phase 1 study with a completion date in 2024 for metastatic melanoma [49]. Mirvetuximab soravtansine is being tested as a first-line treatment for triple-negative breast cancer [50], and in combination with pembrolizumab as a new option for endometrial cancer in a phase 2 study, expected to be completed in 2025 [51]. There are trials with mosunetuzumab for four other conditions: reduction of the tumor with mosunetuzumab in combination with polatuzumab vedotin for refractory, relapsed, or aggressive non-Hodgkin lymphoma in a phase 2 study [52]; a phase 1 study to test mosunetuzumab to treat B-cell lymphoma after replacement of patient's stem cellsby autologous stem cell transplant [53]; and a phase 1 study assessing the efficacy of mosunetuzumab in relapsed or refractory chronic lymphocytic leukemia (CLL) [54]. All of these three studies have a completion date expected in 2027. There is still a phase 1 study testing mosunetuzumab for systemic lupus erythematosus, with a completion date expected in 2024 [55]. None of these studies have posted results yet. Regarding techistanab, ongoing trials were not found for a disease other than multiple myeloma.