Table 2.
Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) reported in patients treated with immune checkpoint inhibitor mAbsa
| mAb | Patients N, regimen, tumor type | ADA assay | ADA % | NAb % | Reference | Year |
|---|---|---|---|---|---|---|
| Anti-PD-1 | ||||||
| Nivolumab | N = 1086, pool of 6 clinical studies | ECL | 12.7 | 0.8 | Agrawal et al. | 2017 |
| N = 2085 | ECL | 11.2 | 0.7 | US PI | 2018 | |
| Nivo 3 mg/kg followed by ipi 1 mg/kg Q3W | NR | 23.8-26 ADA to nivo |
0.5–1.9 nivo NAb |
US PI | 2018 | |
| Nivo 1 mg/kg followed by ipi 3 mg/kg Q3W | NR | 37.8 ADA to nivo |
4.6 nivo NAb |
US PI | 2018 | |
| Nivo followed by ipi | NR | 4.1–8.4 ADA to ipi |
0–0.3 ipi NAb |
US PI | 2018 | |
| Pembrolizumab | N = 1087 | ECL | 1.7 | NR | Van Vugt et al. | 2016 |
| NSCLC | ECL | 2.5 | NR | Van Vugt et al. | 2016 | |
| melanoma | ECL | 0.7 | NR | Van Vugt et al. | 2016 | |
| N = 1289b | ECL | 2.1 | 0.5 | US PI | 2018 | |
| Cemiplimab | N = 398 | ECL | 1.3 | NR | US PI | 2018 |
| Anti-CTLA-4 | ||||||
| Ipilimumab | N = 1024, melanoma | ECL | 1.1 | 0 | US PI | 2018 |
| N = 144, melanomac | ECL | 4.9 | 0 | US PI | 2018 | |
| Nivo and ipi, N = 499, RCC and mCRC | NR | 5.4 ADA to ipi |
0 ipi NAb |
US PI | 2018 | |
| N = 31, melanoma | Bead-based assay | 26 | NR | Knerveland et al. | 2018 | |
| Anti-PD-L1 | ||||||
| Atezolizumab | N = 2007 | NR | 39.1 | NR | EMA | 2017 |
| N = 111 (cohort 1), urothelial carcinoma | NR | 48 | NR | US PI | 2018 | |
| N = 275 (cohort 2), urothelial carcinoma | NR | 42 | NR | US PI | 2018 | |
| N = 565, NSCLC | NR. | 30 | NR | US PI | 2018 | |
| Avelumab | N = 1558 | NR | 4.1 | NR | US PI | 2017 |
| N = 1738d | NR | 5.9 | NR | EMA | 2017 | |
| Durvalumab | N = 1570 | NR | 2.9 | NR | US PI | 2018 |
| Durvalumab + tremelimumab, N = 60 | ECL | 6.6 ADA to durva |
NR | Antonia et al | 2016 | |
| Durvalumab + tremelimumab, N = 53 | ECL | 1.8 ADA to trem |
NR | Antonia et al | 2016 | |
ADA anti-drug antibody, durva durvalumab, CTLA-4 cytotoxic T-lymphocyte associated protein 4, ECL electrochemiluminescent bridging assay, EMA European Medicines Agency, ipi ipilimumab, mAb monoclonal antibody, mCRC metastatic colorectal cancer, NHL non-Hodgkin lymphoma, NAb neutralizing antibody, nivo nivolumab, NR not reported, NSCLC non-small-cell lung cancer, PD-1 programmed death 1, PD-L1 PD-ligand 1, Q2W every 2 weeks, Q3W every 3 weeks, RCC renal cell carcinoma, trem tremelimumab, US PI United States product information
aAll mAbs were administered intravenously
bAnalysis performed in patient samples with concentrations below the drug tolerance level of the ADA assay
cADA assessed using an ECL assay with improved drug tolerance
dAssay performed with a cut point known to provide adequate assay sensitivity and drug tolerance level