Exclusion criteria comprise uncontrolled CNS metastases, investigational drug use within 4 weeks prior, AGS-16C3F hypersensitivity, thromboembolic events (≤3 months), severe cardiac conditions (e.g., CHF Class III/IV), major surgery within 4 weeks, pregnancy/lactation, HIV/hepatitis B/C positivity, active infections requiring systemic treatment, or recent eye surgery/cataracts affecting vision.

Eligible participants include metastatic RCC patients (clear cell/non-clear cell or papillary histology) with prior anti-VEGFR therapy (clear cell) or ENPP3+ status (non-clear cell/papillary). Key requirements: measurable disease (RECIST 1.1), ECOG 0-1, adequate hematologic (ANC ≥1.5x10⁹/L, platelet ≥100x10⁹/L, Hb ≥9 g/dL), renal (creatinine ≤1.5xULN or GFR >50 mL/min), and hepatic function (AST/ALT ≤2.5xULN or ≤5xULN with metastases; bilirubin ≤1.5xULN). Contraception is mandated for participants of childbearing potential.

Exclusion criteria comprised prior axitinib/AGS-16C3F treatment, untreated or unstable brain metastases (>3 months post-radiation/surgery if treated), uncontrolled hypertension (>150/90), GI disorders affecting absorption, active ocular conditions (e.g., infections, corneal ulcers, glaucoma), strong CYP3A4/5 inhibitors/inducers use within 14 days, thromboembolic events (≤4 weeks unless anticoagulated), bleeding disorders (≤2 months), severe cardiac disease (NYHA Class III/IV, MI ≤6 months), major surgery ≤4 weeks, pregnancy/lactation, unresolved infections, or inability to comply with study protocols.

The study assessed Progression-Free Survival (PFS) per RECIST v1.1 by investigator (up to 53 months) and central radiology review (up to 40 months), along with Objective Response Rate (ORR), Duration of Response (DOR), Overall Survival (OS), and Disease Control Rate (DCR). Pharmacokinetic parameters (Cmax, Ctrough, Tmax, AUC₀- ₂₁, t₁/ ₂) for ADC, TAb, and Cys-mcMMAF were evaluated over 21-day cycles. Adverse events (AEs) were monitored for 53 months, with serious AEs requiring intervention or hospitalization.

Exclusion criteria comprise uncontrolled CNS metastases, investigational drug use within 4 weeks prior, AGS-16C3F hypersensitivity, thromboembolic events (≤3 months), severe cardiac conditions (e.g., CHF Class III/IV), major surgery within 4 weeks, pregnancy/lactation, HIV/hepatitis B/C positivity, active infections requiring systemic treatment, or recent eye surgery/cataracts affecting vision.

Eligible participants include metastatic RCC patients (clear cell/non-clear cell or papillary histology) with prior anti-VEGFR therapy (clear cell) or ENPP3+ status (non-clear cell/papillary). Key requirements: measurable disease (RECIST 1.1), ECOG 0-1, adequate hematologic (ANC ≥1.5x10⁹/L, platelet ≥100x10⁹/L, Hb ≥9 g/dL), renal (creatinine ≤1.5xULN or GFR >50 mL/min), and hepatic function (AST/ALT ≤2.5xULN or ≤5xULN with metastases; bilirubin ≤1.5xULN). Contraception is mandated for participants of childbearing potential.

Exclusion criteria comprised prior axitinib/AGS-16C3F treatment, untreated or unstable brain metastases (>3 months post-radiation/surgery if treated), uncontrolled hypertension (>150/90), GI disorders affecting absorption, active ocular conditions (e.g., infections, corneal ulcers, glaucoma), strong CYP3A4/5 inhibitors/inducers use within 14 days, thromboembolic events (≤4 weeks unless anticoagulated), bleeding disorders (≤2 months), severe cardiac disease (NYHA Class III/IV, MI ≤6 months), major surgery ≤4 weeks, pregnancy/lactation, unresolved infections, or inability to comply with study protocols.

The study assessed Progression-Free Survival (PFS) per RECIST v1.1 by investigator (up to 53 months) and central radiology review (up to 40 months), along with Objective Response Rate (ORR), Duration of Response (DOR), Overall Survival (OS), and Disease Control Rate (DCR). Pharmacokinetic parameters (Cmax, Ctrough, Tmax, AUC₀- ₂₁, t₁/ ₂) for ADC, TAb, and Cys-mcMMAF were evaluated over 21-day cycles. Adverse events (AEs) were monitored for 53 months, with serious AEs requiring intervention or hospitalization.

Exclusion criteria comprised prior axitinib/AGS-16C3F treatment, untreated or unstable brain metastases (>3 months post-radiation/surgery if treated), uncontrolled hypertension (>150/90), GI disorders affecting absorption, active ocular conditions (e.g., infections, corneal ulcers, glaucoma), strong CYP3A4/5 inhibitors/inducers use within 14 days, thromboembolic events (≤4 weeks unless anticoagulated), bleeding disorders (≤2 months), severe cardiac disease (NYHA Class III/IV, MI ≤6 months), major surgery ≤4 weeks, pregnancy/lactation, unresolved infections, or inability to comply with study protocols.

The study assessed Progression-Free Survival (PFS) per RECIST v1.1 by investigator (up to 53 months) and central radiology review (up to 40 months), along with Objective Response Rate (ORR), Duration of Response (DOR), Overall Survival (OS), and Disease Control Rate (DCR). Pharmacokinetic parameters (Cmax, Ctrough, Tmax, AUC₀- ₂₁, t₁/ ₂) for ADC, TAb, and Cys-mcMMAF were evaluated over 21-day cycles. Adverse events (AEs) were monitored for 53 months, with serious AEs requiring intervention or hospitalization.

Disease Control Rate (DCR)=13.40% (95% CI,6.3-24.0) for AGS16C3F, Disease Control Rate (DCR)=22.70% (95% CI,13.30-34.70) for axitinib. Median duration of Response (mDoR)=6.80 months (95% CI,3.80-18.40) for AGS16C3F, Median duration of Response (mDoR)=6.7 months (95% CI,1.80-9.20) for axitinib. Objective Response Rate (ORR)=7.50% (95% CI,2.50-16.60) for AGS16C3F, Objective Response Rate (ORR)=18.20% (95% CI,9.80-29.60) for axitinib. Median Overall Survival (mOS)=13.10 months for AGS16C3F, Median Overall Survival (mOS)=15.40 months for axitinib.