Table 2.

Summary of clearance of non-ICI mAbs.

Drug name	IgG Type	${\text{CL}}_0$ (L/day)	${\text{CL}}_0$ covariates									Time-varying CL	${\text{CL}}_0$-outcome relationship	$\text{ΔCL}$-outcome relationship
			WT	ALB	TS	Male	eGFR CrCL	Liver function	PS ≥1	ADA	Other
Bevacizumab (41,44,167,168)	IgG1 aVGEF	0.207	↑↑	↓↓	/	+	/	ALP(↑)	+	/	$\text{IFNα}$ combined(−) VGEF (↑) CEA (↑) Total protein (↓) SUVmax change (↑) Extra-hepatic metastases (+) Advanced gastric cancer (+) No prior gastrectomy (+)	No	Trend of lower ${\text{CL}}_0$ in CR group	/
Trastuzumab (30,40,42,45,169)	IgG1 aHER2	0.180–0.230	↑↑	↓↓	/	/	/	ALT(↑)	/	/	No prior gastrectomy (+) Metastases sites (↑)	No (Time-dependent increase in Vc was reported in early-stage breast cancer)	/	/
Cetuximab (35–39)	IgG1 Chimeric aEGFR	0.418–0.570	/	↓	/	/	/	/	/	/	BSA (↑) Chemotherapy(−)	Yes (Emax 23.1%; ${\text{T}}_{50}$ 143.5 days)	CL (global) -OS/PFS (HNSCC and CRC)	$\text{ΔCL}$-BOR (CRC)
Rituximab (46,47,49,170–178)	IgG1 Chimeric aCD20	0.14–0.54	↑↑	/	↑	+	/	/	/	/	BSA (↑↑) WBC(↑) CD20/CD19 count(↑) Endogenous IgG(↑) Disease type Combined regimens FCGR3A polymorphism	Yes (decrease ~88%; ${\text{T}}_{50}$ ~ 17 – 34 days)	(Ctrough/AUC on first dose with PFS and BOR)	(A faster increase of CL correlated with no progression)
Obinutuzumab (50,179)	IgG1 Glycoengineered aCD20	0.238–0.314	↑↑	↓↓	↑	+	/	/	/	/	Age (↓) Disease type	Yes (decrease ~26.4–32.5%; ${\text{T}}_{50}$ 9–19 days)	(Cmean correlated with BOR and PFS)	/
Ocrelizumab (180)	IgG1 Glycoengineered aCD20	0.189–0.218	↑↑	/	/	/	/	/	/	/	/	Yes (decrease ~20%; ${\text{T}}_{50}$ ~32 weeks)	/	/
Infliximab (57–60,181–184)	IgG1 Chimeric $\text{aTNFα}$	0.2–0.38	↑↑	↓↓	/	+	/	/	/	+	Disease type Time-varying disease activity Time-varying CRP(↑) Azathioprine cotreatment (−)	Yes (linear increase: 0.0348 L/day/year in IBD)	CL at de-escalation-risk of relapse in IBD	/
Adalimumab (129,185–189)	IgG1 $\text{aTNFα}$	0.24–0.59	↑↑	↓↓	/	+	/	/	/	+	Time-varying CRP(↑) Concomitant methotrexate Baseline rheumatoid factor	Yes (Driven by time-varying covariates)	/	/
Daratumumab [67–70]	IgG1 aCD38	0.171	↑↑	↓↓	/	/	/	/	/	/	Disease type (IgG vs. non-IgG multiple myeloma) Drug products (Phase 2 vs. Phase 3 product)	Yes (decrease ~29%)	(Ctrough,max correlated with ORR)	/

(↑/+, positive correlation; ↓/−, negative correlation; /, not reported; WT, weight; ALB, albumin; TS, tumor size; CrCL, serum creatinine clearance; PS, performance status; ADA, anti-drug antibody; ALP, alkaline phosphatase; ALT, alanine aminotransferase; VEGF, vascular endothelial growth factor; CEA, carcinoembryonic antigen; SUV, standardized uptake value; WBC, white blood cell; HNSCC, head and neck squamous cell carcinoma; CRC, colorectal cancer; BOR, best overall response; IBD, inflammatory bowel diseases). References are cited under the drug name.