Summary of potential anti-PD-L1 monoclonal antibodies, describing their clinical trials, FDA approval, and recommended dosages [208–223]
| PD-L1 inhibitor | Description | Salient clinical trials summary | Results of the observations |
|---|---|---|---|
| Nivolumab | An IgG4 fully human mAb which functions against PD-1 by disrupting its binding with PD-L1 & the henceforth downstream signaling that inhibits the antitumor T-cells | Two phase III clinical trials, CHECKMATE 017 and CHECKMATE 057 on patients who had progressed after platinum-based doublet chemotherapy Not suitable for PS of 2 or symptomatic brain metastasis | FDA approval in October 2015 for treating metastatic patients on or after platinum chemotherapy. Recommended dose: 3 mg/kg intravenously every 2 weeks. |
| Pembrolizumab | An IgG4 humanized antibody directed against PD-1 | Screened as second-line NSCLC treatment (KEYNOTE-001) One phase II/II (KEYNOTE-010) and the second phase III (KEYNOTE-024) trial | KEYNOTE-001: accelerated FDA approval in October 2015 for tumors expressing PD-L1 and a disease progression on or after platinum chemotherapy. Other trials conferred FDA approval in October 2016 for first-line treatment of metastatic patients having 50% or more cells expressing PD-L1 with no EGFR or ALK aberrations & prior systemic chemotherapy. Recommended dose: 200 mg intravenously every 3 weeks. |
| Atezolizumab | A human IgG1 mAb which targets the protein PD-L1 | Phase II (POPLAR) and a phase III (OAK) trials A phase II (BIRCH: exploring the efficacy as 1st, 2nd and 3rd line drug after platinum therapy), phase III (Impower-150: combined delivery with carboplatin, paclitaxel, and bavacizumab) and a phase II (CITYSCAPE: combined delivery with tiragolumab) | POPLAR and OAK trials conferred FDA approval in October 2016 for treating patients having disease progressed on or after platinum chemotherapy. Recommended dose: 1,200 mg intravenously every 3 weeks. Other trials ensured a first-line usage as monotherapy or in combination with immunotherapy. |
| Durvalumab | A fully human IgG1 mAb binds PD-L1 on tumor cells | A phase II (ATLANTIC, 44 patients, administered after two rounds of chemotherapy) and a phase III PACIFIC (713 patients with stage III disease, administered after two or more cycles of platinum chemotherapy) | FDA approval in February 2018 for treating unresectable stage III tumors that have not progressed following platinum chemotherapy and radiation therapy. Recommended dose: 10 mg/kg intravenously every 2 weeks. |
| Avelumab | An entirely human IgG1 mAb that targets PD-L1 possesses a characteristic antibody-dependent cell-mediated cytotoxicity which is missing in other PD-L1 inhibitors | Phase 1b (JAVELIN, 184 stage IIIB or IV patients progressive on platinum chemotherapy) and phase III (JAVELIN, 792 stage IIIB or IV sufferers exhibiting disease progression on platinum chemotherapy were randomly administered avelumab every 2 weeks or docetaxel every 3 weeks | Phase 1b trial achieved 50% disease control as the best response. Phase III trial revealed a better safety profile in avelumab-administered sufferers (64%) against the 86% for docetaxel. The trial is still ongoing but enrolment is closed. |
PS: performace status
