Table 1.

Summary of ICI clearance and clearance-response relationship.

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	Emax	${\text{T}}_{50}$ (days)	Covariates
Pembrolizumab (7,17,23,33,160)	IgG4 S228P aPD1	0.219–0.249	/	↓↓	↑	+	↑	BIL (↓)	+	/	/	21.7%	67.4	ALB, LDH, TS, ALC (Longitudinal)	${\text{CL}}_0$-OS (MEL, NSCLC)	$\text{ΔCL}$-BOR (MEL, NSCLC)
Nivolumab (±Ipilimumab) (22,29,32,161–164)	IgG4 S228P aPD1	0.225–0.259	↑↑	↓↓	/	+	↑	/	+	/	Asian (−) AA (+)	21.3%−27.7%	52.9–91.7	ALB on Emax TS on Emax IPI on Emax PS on Emax	${\text{CL}}_0$-OS ${\text{CL}}_0$-PFS (NSCLC, RCC, MEL)	$\text{ΔCL}$-BOR (RCC, MEL, NSCLC)
Cemiplimab (24)	IgG4 S228P aPD1	0.290	↑	↓↓	↑	/	/	ALT (↓)	/	+	IGG (↑)	33.6%	28.9	Cancer type on Emax Cancer type on ${\text{T}}_{50}$ Race on ${\text{T}}_{50}$	/	$\text{ΔCL}$-BOR (CSCC)
Dostarlimab	IgG4 S228P aPD1	0.163	↑↑	↓↓	/	+	/	ALT/ALP(↑)	/	/	AGE (↓)	15.4%	90.8	/	/	/
Atezolizumab (131,165)	IgG1 Fc mutant* Aglycosylation aPD-L1	0.235	↑↑	↓↓	↑	+	/	ALP(↑) BIL(↓)	/	+	NEU(↑)	22.0%	447	SLD, ALB, WT, ALP, NEU, BIL, ADA (Longitudinal)	/	/
Avelumab (25)	IgG1 aPD-L1	0.739	↑	↓	↑	+	↑	/	+	+	AGE (↓) CRP(↑) AA(−)	0–32.1%	131	Cancer type on Emax and T50	/	$\text{ΔCL}$-BOR (MCC, UC)
Durvalumab (62,132)	IgG1 Fc mutant* aPD-L1	0.232–0.257	↑↑	↓↓	↑	+	↑	/	+	+	IGG(↑) sPD-L1(↑) LDH(↑)	16.9%	173.1	ALB, TS, IGG, sPD-L1, LDH (Longitudinal)	/	/
Relatlimab (+Nivolumab) (FDA PI)	IgG4 S228P Fc mutant* aLAG-3	0.167	↑↑	↓↓	/	+	↑	/	+	/	/	4.8%	133	PS on Emax	/	/
Ipilimumab (±Nivolumab) (26,133)	IgG1 aCTLA-4	0.338	↑↑	/	/	/	/	/	/	+	LDH (↑↑)	6.4% (IPI)	106	23.5% (IPI+Nivo)	/	$\text{ΔCL}$-BOR (MEL, NSCLC, other)
Tremelimumab (15,16)	IgG2 aCTLA-4	0.26 – 0.31	/	/	↑	+	↑	/	+	/	IGG (↑) LDH (↑) CRP (↑)	/	/	/	${\text{CL}}_0$-OS (MEL)	/
Bintrafusp alfa (166)	IgG1# aPD-L1 and aTGF-$\text{β}$	0.379	/	/	/	/	/	/	/	/	/	/	/	/##	/	/

(↑/+, positive correlation; ↓/−, negative correlation; /, not reported; WT, weight; ALB, albumin; TS, tumor size; CrCL, serum creatinine clearance; PS, performance status; ADA, anti-drug antibody; Emax, percentage of clearance decrease from baseline to steady state; ${\text{T}}_{50}$, time to 50% of maximum reduction of clearance; BIL, bilirubin; AA, African American; Chemo, coadministration with chemotherapy; IPI, ipilimumab; IGG, endogenous IgG; NEU, neutrophil; CRP, c-reactive protein; MEL, melanoma; NSCLC, non-small cell lung cancer; UC, urothelial carcinoma; ALC, actual lymphocyte count; RCC, renal cell carcinoma; MCC, merkel cell carcinoma; CSCC, cutaneous squamous cell carcinoma). References are cited under the drug name.

^*Fc mutation: Atezolizumab, N297A; Durvalumab, L234F/L235E/P331S; Relatlimab, unknown

^#IgG1-based bifunctional fusion protein

^##ALB, CRP, and PLT were found to be influential on time-varying CL, but observed data did not show a notable trend of CL decrease over time.