ADC ID	DRG0ZMZUD
ADC Name	Zilovertamab vedotin
Synonyms	zilovertamab vedotin; VLS-101; MK-2140    Click to Show/Hide
Organization	University of California, San Diego (Originator);Oncternal Therapeutics;VelosBio (Top20 MNC)
Drug Status	Phase 3
Drug-to-Antibody Ratio	4
Structure
				2D MOL
Antibody Name	Zilovertamab					Antibody Info
Antigen Name	Inactive tyrosine-protein kinase transmembrane receptor ROR1 (ROR1)					Antigen Info
Payload Name	MMAE					Payload Info
Therapeutic Target	Microtubule (MT)					Target Info
Linker Name	Mc-Val-Cit-PABC					Linker Info
Conjugate Type	Random Cysteines
Combination Type	vedotin

Standard Type	Value	Units	Description	Reference
Time to Maximum Concentration (Tmax)	2	h	Mean cycle 1 pharmacokinetic parameters for total ADC, 0.5 mg/kg, n=1.	[2]
Maximum Observed Concentration (Cmax)	9.6	ug/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 0.5 mg/kg, n=1.	[2]
Area Under the Concentration-Time Curve (AUC)	547	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 0.5 mg/kg, n=1, AUClast.	[2]
Time to Maximum Concentration (Tmax)	2	h	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.0 mg/kg, n=3.	[2]
Maximum Observed Concentration (Cmax)	20.6	ug/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.0 mg/kg, n=3.	[2]
Area Under the Concentration-Time Curve (AUC)	1020	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.0 mg/kg, n=3, AUClast.	[2]
Time to Maximum Concentration (Tmax)	1.7	h	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.5 mg/kg, n=3.	[2]
Maximum Observed Concentration (Cmax)	31.3	ug/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.5 mg/kg, n=3.	[2]
Area Under the Concentration-Time Curve (AUC)	2530	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.5 mg/kg, n=3, AUClast.	[2]
Time to Maximum Concentration (Tmax)	0.5	h	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.25 mg/kg, n=11.	[2]
Maximum Observed Concentration (Cmax)	50	ug/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.25 mg/kg, n=11.	[2]
Area Under the Concentration-Time Curve (AUC)	3220	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.25 mg/kg, n=11, AUClast.	[2]
Time to Maximum Concentration (Tmax)	1.2	h	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.5 mg/kg, n=14.	[2]
Maximum Observed Concentration (Cmax)	49.4	ug/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.5 mg/kg, n=14.	[2]
Area Under the Concentration-Time Curve (AUC)	3570	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.5 mg/kg, n=14, AUClast.	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	547	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 0.5 mg/kg, n=1, AUClast.	[2]
Volume of Distribution (Vd)	82.4	mL/kg	Mean cycle 1 pharmacokinetic parameters for total ADC, 0.5 mg/kg, n=1.	[2]
Area Under the Concentration-Time Curve (AUC)	1020	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.0 mg/kg, n=3, AUClast.	[2]
Volume of Distribution (Vd)	77.8	mL/kg	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.0 mg/kg, n=3.	[2]
Area Under the Concentration-Time Curve (AUC)	2530	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.5 mg/kg, n=3, AUClast.	[2]
Volume of Distribution (Vd)	98.6	mL/kg	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.5 mg/kg, n=3.	[2]
Area Under the Concentration-Time Curve (AUC)	3220	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.25 mg/kg, n=11, AUClast.	[2]
Volume of Distribution (Vd)	88	mL/kg	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.25 mg/kg, n=11.	[2]
Area Under the Concentration-Time Curve (AUC)	3570	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.5 mg/kg, n=14, AUClast.	[2]
Volume of Distribution (Vd)	101	mL/kg	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.5 mg/kg, n=14.	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	547	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 0.5 mg/kg, n=1, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	1020	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.0 mg/kg, n=3, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	2530	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.5 mg/kg, n=3, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	3220	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.25 mg/kg, n=11, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	3570	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.5 mg/kg, n=14, AUClast.	[2]

Standard Type	Value	Units	Description	Reference
Clearance (CL)	0.0203	L/h	A Sequential Population Pharmacokinetic Model of Zilovertamab Vedotin in Patients with Hematologic Malignancies Extrapolated to the Pediatric Population	[1]
Area Under the Concentration-Time Curve (AUC)	547	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 0.5 mg/kg, n=1, AUClast.	[2]
Clearance (CL)	0.89	mL/h/kg	Mean cycle 1 pharmacokinetic parameters for total ADC, 0.5 mg/kg, n=1.	[2]
Elimination Half-Life (t1/2)	2.7	day	Mean cycle 1 pharmacokinetic parameters for total ADC, 0.5 mg/kg, n=1.	[2]
Area Under the Concentration-Time Curve (AUC)	1020	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.0 mg/kg, n=3, AUClast.	[2]
Clearance (CL)	1.01	mL/h/kg	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.0 mg/kg, n=3.	[2]
Elimination Half-Life (t1/2)	2.6	day	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.0 mg/kg, n=3.	[2]
Area Under the Concentration-Time Curve (AUC)	2530	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.5 mg/kg, n=3, AUClast.	[2]
Clearance (CL)	0.584	mL/h/kg	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.5 mg/kg, n=3.	[2]
Elimination Half-Life (t1/2)	5	day	Mean cycle 1 pharmacokinetic parameters for total ADC, 1.5 mg/kg, n=3.	[2]
Area Under the Concentration-Time Curve (AUC)	3220	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.25 mg/kg, n=11, AUClast.	[2]
Clearance (CL)	0.874	mL/h/kg	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.25 mg/kg, n=11.	[2]
Elimination Half-Life (t1/2)	3.6	day	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.25 mg/kg, n=11.	[2]
Area Under the Concentration-Time Curve (AUC)	3570	ug*h/mL	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.5 mg/kg, n=14, AUClast.	[2]
Clearance (CL)	0.712	mL/h/kg	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.5 mg/kg, n=14.	[2]
Elimination Half-Life (t1/2)	4.1	day	Mean cycle 1 pharmacokinetic parameters for total ADC, 2.5 mg/kg, n=14.	[2]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Partial Response (PR)	NCT05458297	PHASE2	A Multicenter, Open-label, Phase 2 Basket Study to Evaluate the Safety and Efficacy of MK-2140 as a Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (waveLINE-006)    Click to Show/Hide
Objective Response Rate (ORR)	NCT05144841	PHASE2	A Phase 2 Open-label Clinical Study to Evaluate the Efficacy and Safety of Zilovertamab Vedotin (MK-2140) in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-004)
Objective Response Rate (ORR)	NCT05458297	PHASE2	A Multicenter, Open-label, Phase 2 Basket Study to Evaluate the Safety and Efficacy of MK-2140 as a Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (waveLINE-006)    Click to Show/Hide
Complete response (CR)	NCT05458297	PHASE2	A Multicenter, Open-label, Phase 2 Basket Study to Evaluate the Safety and Efficacy of MK-2140 as a Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (waveLINE-006)    Click to Show/Hide
Undisclosed	NCT03833180	PHASE1	A Phase 1 Dose-Escalation and Cohort-Expansion Study of VLS-101 in Subjects With Hematological Malignancies (waveLINE-001)
Undisclosed	NCT05406401	PHASE2	A Multicenter, Open-label, Phase 2 Dose Escalation and Confirmation, and Efficacy Expansion Study of Zilovertamab Vedotin (MK-2140) in Combination With R-CHP in Participants With DLBCL (waveLINE)
Undisclosed	NCT05139017	PHASE2|||PHASE3	A Phase 2/3 Multicenter, Open-label, Randomized, Active-Control Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-003)    Click to Show/Hide
Undisclosed	NCT06717347	PHASE3	A Randomized, Open-Label, Multicenter, Phase 3 Study of Zilovertamab Vedotin (MK-2140) in Combination With R-CHP Versus R-CHOP in Participants With Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL) (waveLINE-010)    Click to Show/Hide
Undisclosed	NCT06395103	PHASE1|||PHASE2	LIGHTBEAM-U01 Substudy 01A: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors
Undisclosed	NCT04504916	PHASE2	A Phase 2 Study of VLS-101 in Patients With Solid Tumors
Undisclosed	NCT05562830	PHASE1|||PHASE2	A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants With PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A    Click to Show/Hide
Objective Response Rate (ORR)	NCT05144841	Phase 2	A phase 2 open-label clinical study to evaluate the efficacy and safety of zilovertamab vedotin (MK-2140) in participants with relapsed or refractory diffuse large B-cell lymphoma (waveline-004).
Objective Response Rate (ORR)	NCT03833180	Phase 1	A phase 1 dose-escalation and cohort-expansion study of VLS-101 in subjects with hematological malignancies (waveline-001).
Undisclosed	NCT05139017	Phase 2/3	A phase 2/3 multicenter, open-label, randomized, active-control study of zilovertamab vedotin (MK-2140) in combination with standard of care in participants with relapsed or refractory diffuse large B-cell lymphoma (waveline-003).    Click to Show/Hide
Undisclosed	NCT05458297	Phase 2	A multicenter, open-label, phase 2 basket study to evaluate the safety and efficacy of MK-2140 as a monotherapy and in combination in participants with aggressive and indolent B-cell malignancies.
Undisclosed	NCT05406401	Phase 2	A multicenter, open-label, phase 2 dose escalation and confirmation, and efficacy expansion study of zilovertamab vedotin (MK-2140) in combination with r-chp in participants with DLBCL (waveline).
Undisclosed	NCT05562830	Phase 1/2	A phase 1/2 open-label rolling-arm umbrella platform study of investigational agents with or without pembrolizumab in participants with PD-1/L1 refractory locally advanced or metastatic urothelial carcinoma (keymaker-u04): substudy 04a.    Click to Show/Hide
Undisclosed	NCT04504916	Phase 1	A phase 2 study of VLS-101 in patients with solid tumors.

Standard Type	Value	Units	Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI)	≈ 0	%	Richter syndrome PDX model (PDX: RS9737)
Tumor Growth Inhibition value (TGI)	≈ 0	%	Richter syndrome PDX model (PDX: RS9737)
Tumor Growth Inhibition value (TGI)	≈ 88.8	%	Richter syndrome PDX model (PDX: IP867/17)
Tumor Growth Inhibition value (TGI)	≈ 90.9	%	Richter syndrome PDX model (PDX: RS9737)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Richter syndrome PDX model (PDX: RS9737)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Richter syndrome PDX model (PDX: RS9737)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Richter syndrome PDX model (PDX: RS9737)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Richter syndrome PDX model (PDX: IP867/17)

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Partial Response (PR)	32%
Patients Enrolled	Key eligibility requires relapsed/refractory B-cell malignancies (MCL post ≥2 therapies including BTKi+CAR-T; FL/CLL post ≥2 lines) with histologic confirmation (WHO 2016). Exclusions encompass active CVD, Grade >1 neuropathy, prior solid organ transplant, uncontrolled infections (HBV/HCV/HIV), recent anticancer therapy (within 2-4 weeks), CNS lymphoma, or corticosteroid use >30mg prednisone equivalent. HBV+ candidates require antiviral therapy with undetectable viral load.    Click to Show/Hide
Administration Dosage	Participants will receive either zilovertamab vedotin IV infusion Dose 1/2 every 3 weeks (Q3W) until disease progression or discontinuation.
Related Clinical Trial
NCT Number	NCT05458297	Clinical Status	PHASE2
Clinical Description	A Multicenter, Open-label, Phase 2 Basket Study to Evaluate the Safety and Efficacy of MK-2140 as a Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (waveLINE-006)
Primary Endpoint	Safety outcomes include AE rates (up to 57 months) across cohorts (MCL-C, FL-D, CLL), treatment discontinuations due to AEs, and DLTs in MCL-C (per CTCAE v5.0). Efficacy measures feature ORR by disease type - MCL-A/RT/FL-D&E via Lugano criteria (BICR), MCL-C via Lugano (investigator), and CLL via iwCLL criteria.
Other Endpoint	Secondary endpoints assess DOR by Lugano criteria (BICR for MCL-A/RT/FL-D&E; investigator for MCL-C) and iwCLL (CLL), tracking time from response to progression/death. Additional safety data includes AE incidence and treatment discontinuations in MCL-A/RT/FL-E cohorts over ~57 months.
Experiment 2 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Objective Response Rate (ORR)	30%
Patients Enrolled	Eligible patients must have rrDLBCL failing ≥2 prior therapies (including alkylator/anthracycline/anti-CD20) and be post-CAR-T failure or ineligible, with ECOG 0-2 and adequate organ function. Exclusions: PMBCL, solid organ transplants, active cardiovascular/liver disease, neuropathy (>Grade 1), transformed DLBCL, GVHD, recent anticancer therapies/vaccines, uncontrolled infections, HIV/HBV/HCV, or CNS involvement. Prednisone >30mg/day or live vaccines within 30 days are prohibited.    Click to Show/Hide
Administration Dosage	Participants will receive treatment with zilovertamab vedotin 2.5 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks (Q3W)) until documented disease progression or any other discontinuation criterion is met.
Related Clinical Trial
NCT Number	NCT05144841	Clinical Status	PHASE2
Clinical Description	A Phase 2 Open-label Clinical Study to Evaluate the Efficacy and Safety of Zilovertamab Vedotin (MK-2140) in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-004)
Primary Endpoint	The objective response rate (ORR) is defined as the percentage of participants achieving complete response (CR) or partial response (PR) per Lugano 2014 criteria, assessed by blinded independent central review (BICR), in relapsed/refractory DLBCL patients treated with zilovertamab vedotin Q3W. CR requires full radiologic resolution, while PR necessitates ≥50% reduction in tumor burden across target lesions.    Click to Show/Hide
Other Endpoint	Duration of response (DOR) measures time from first CR/PR to disease progression/death. Safety evaluations include adverse event (AE) incidence and treatment discontinuations due to AEs over 50 months, with AEs defined as any treatment-associated medical occurrences regardless of causality.
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Objective Response Rate (ORR)	64%
Patients Enrolled	Key eligibility requires relapsed/refractory B-cell malignancies (MCL post ≥2 therapies including BTKi+CAR-T; FL/CLL post ≥2 lines) with histologic confirmation (WHO 2016). Exclusions encompass active CVD, Grade >1 neuropathy, prior solid organ transplant, uncontrolled infections (HBV/HCV/HIV), recent anticancer therapy (within 2-4 weeks), CNS lymphoma, or corticosteroid use >30mg prednisone equivalent. HBV+ candidates require antiviral therapy with undetectable viral load.    Click to Show/Hide
Administration Dosage	Participants will receive either zilovertamab vedotin IV infusion Dose 1/2 every 3 weeks (Q3W) until disease progression or discontinuation.
Related Clinical Trial
NCT Number	NCT05458297	Clinical Status	PHASE2
Clinical Description	A Multicenter, Open-label, Phase 2 Basket Study to Evaluate the Safety and Efficacy of MK-2140 as a Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (waveLINE-006)
Primary Endpoint	Safety outcomes include AE rates (up to 57 months) across cohorts (MCL-C, FL-D, CLL), treatment discontinuations due to AEs, and DLTs in MCL-C (per CTCAE v5.0). Efficacy measures feature ORR by disease type - MCL-A/RT/FL-D&E via Lugano criteria (BICR), MCL-C via Lugano (investigator), and CLL via iwCLL criteria.
Other Endpoint	Secondary endpoints assess DOR by Lugano criteria (BICR for MCL-A/RT/FL-D&E; investigator for MCL-C) and iwCLL (CLL), tracking time from response to progression/death. Additional safety data includes AE incidence and treatment discontinuations in MCL-A/RT/FL-E cohorts over ~57 months.
Experiment 4 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Complete response (CR)	32%
Patients Enrolled	Key eligibility requires relapsed/refractory B-cell malignancies (MCL post ≥2 therapies including BTKi+CAR-T; FL/CLL post ≥2 lines) with histologic confirmation (WHO 2016). Exclusions encompass active CVD, Grade >1 neuropathy, prior solid organ transplant, uncontrolled infections (HBV/HCV/HIV), recent anticancer therapy (within 2-4 weeks), CNS lymphoma, or corticosteroid use >30mg prednisone equivalent. HBV+ candidates require antiviral therapy with undetectable viral load.    Click to Show/Hide
Administration Dosage	Participants will receive either zilovertamab vedotin IV infusion Dose 1/2 every 3 weeks (Q3W) until disease progression or discontinuation.
Related Clinical Trial
NCT Number	NCT05458297	Clinical Status	PHASE2
Clinical Description	A Multicenter, Open-label, Phase 2 Basket Study to Evaluate the Safety and Efficacy of MK-2140 as a Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (waveLINE-006)
Primary Endpoint	Safety outcomes include AE rates (up to 57 months) across cohorts (MCL-C, FL-D, CLL), treatment discontinuations due to AEs, and DLTs in MCL-C (per CTCAE v5.0). Efficacy measures feature ORR by disease type - MCL-A/RT/FL-D&E via Lugano criteria (BICR), MCL-C via Lugano (investigator), and CLL via iwCLL criteria.
Other Endpoint	Secondary endpoints assess DOR by Lugano criteria (BICR for MCL-A/RT/FL-D&E; investigator for MCL-C) and iwCLL (CLL), tracking time from response to progression/death. Additional safety data includes AE incidence and treatment discontinuations in MCL-A/RT/FL-E cohorts over ~57 months.
Experiment 5 Reporting the Activity Date of This ADC					[5]
Patients Enrolled	Eligible patients (≥18 years, ECOG 0-2) must have relapsed/refractory CLL/SLL, NHL (MCL/FL/DLBCL/etc.), ALL, or AML with measurable disease and adequate organ function. Key exclusions include CNS malignancy, uncontrolled infections, Grade >1 neuropathy, recent major surgery, strong CYP3A4 modulators, HSCT/CAR-T candidates, prior ROR1-targeted therapy, or concurrent corticosteroids >30mg prednisone equivalent. Baseline tumor tissue and resolution of prior therapy toxicities (≤Grade 1) are required.    Click to Show/Hide
Administration Dosage	Participants will be administered escalating doses of zilovertamab vedotin at 0.50, 1.00, 1.50, 2.25, 2.50, 2.75, and 3.00 mg/kg IV on Day 1 of repeated 21-day cycles (Q1/3W); Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1 and 8 of repeated 21-day cycles (Q2/3W); Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1, 8, and 15 of repeated 21-day cycles (Q3/4W).    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT03833180	Clinical Status	PHASE1
Clinical Description	A Phase 1 Dose-Escalation and Cohort-Expansion Study of VLS-101 in Subjects With Hematological Malignancies (waveLINE-001)
Primary Endpoint	The primary objectives focus on determining the MTD of zilovertamab vedotin (highest dose with ≤17% DLT rate in Cycle 1) and establishing the RDR considering safety, PK/PD, and efficacy data during the initial 21-day cycle.
Other Endpoint	Key safety assessments include TEAEs, SAEs, AESIs (Grade ≥3 infusion reactions, TLS, peripheral neuropathy), treatment discontinuations, and DLTs over ~3.5 years. Pharmacokinetic parameters (Cmax, Tmax, AUC, Vd, CL, t½) for zilovertamab vedotin, UC-961 antibody, and MMAE will be evaluated across treatment cycles (up to ~3.5 years), alongside immunogenicity (anti-drug antibodies) and efficacy measures (OR, CRMRD-, tumor dimension changes, TTR, DOR, PFS, TTF, OS) in hematologic malignancies.    Click to Show/Hide
Experiment 6 Reporting the Activity Date of This ADC					[6]
Patients Enrolled	Eligibility requires untreated, PET-positive DLBCL (Lugano 4-5) confirmed by BICR, ECOG 0-1. Exclusions encompass transformed lymphoma, organ transplant history, active CVD (recent MI/stroke, NYHA &ge;II), Grade >1 neuropathy, prior radiotherapy (<28 days), corticosteroids >30mg prednisone daily, strong CYP3A4 modulators (<7 days), active infections (HBV/HCV/HIV), CNS involvement, or second malignancies (<2 years remission except certain skin cancers).    Click to Show/Hide
Administration Dosage	Approximately 60 patients will be enrolled (part 1, n = 45; part 2, n = 15). Part 1 will use a modified toxicity probability interval design to establish the RP2D of ZV when administered with R-CHP. The starting dose of ZV will be 1.75 mg/kg (modified to 1.5, 2.0, 2.25, or 2.5 mg/kg) administered as an intravenous infusion every 3 weeks (Q3W) in combination with R-CHP.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT05406401	Clinical Status	PHASE2
Clinical Description	A Multicenter, Open-label, Phase 2 Dose Escalation and Confirmation, and Efficacy Expansion Study of Zilovertamab Vedotin (MK-2140) in Combination With R-CHP in Participants With DLBCL (waveLINE)
Primary Endpoint	Safety assessments focus on DLTs per CTCAE v5.0 during Cycle 1 (21 days), overall AE incidence (up to 8 months), and treatment discontinuations due to AEs (up to 5.5 months). Efficacy measures include CRR and ORR per Lugano criteria (investigator-assessed via CT/MRI/PET imaging and clinical findings) with reporting through ~60 months.
Other Endpoint	Key efficacy analysis evaluates DOR (time from first CR/PR to progression/death) per Lugano criteria (investigator-assessed via imaging/clinical evaluation) over ~60 months, alongside ORR reporting (CR+PR rates) for the same period.
Experiment 7 Reporting the Activity Date of This ADC					[7]
Patients Enrolled	Eligibility requires histologically confirmed DLBCL (Lugano-measurable, ECOG 0-2) with relapsed/refractory status post &ge;1 prior therapy (including ASCT/CAR-T failure). Exclusions: transformed DLBCL, organ transplant history, active CVD/GVHD, Grade >1 neuropathy, second malignancy (<2 years remission), recent anticancer therapy/radiotherapy (4 weeks), CNS involvement, active infections (HIV/HCV), or uncontrolled psychiatric/substance disorders. Prior CNS disease requires confirmed remission.    Click to Show/Hide
Administration Dosage	Approximately 420 patients will be enrolled in the study (cohort A, n = 230; cohort B, n = 190). In the part 1 dose confirmation phase, 30 patients from cohort A will receive ZV (at increasing doses: 1.5, 1.75, 2.0, 2.25, and 2.5 mg/kg; starting at 1.75 mg/kg) plus gemcitabine-oxaliplatin + rituximab (R-GemOx) to establish the recommended phase 2 dose using the mTPI design.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT05139017	Clinical Status	PHASE2|||PHASE3
Clinical Description	A Phase 2/3 Multicenter, Open-label, Randomized, Active-Control Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-003)
Primary Endpoint	Safety analysis includes dose-limiting toxicities (DLTs) in Part 1 (6 weeks, per CTCAE v5.0), overall AE incidence (68 months), and treatment discontinuations due to AEs (68 months). Key efficacy endpoints are overall survival (OS, 35 months) and progression-free survival (PFS, 26 months) - both assessed from randomization to disease progression (Lugano/BICR) or death.    Click to Show/Hide
Other Endpoint	Response evaluation comprises objective response rate (ORR, 26 months) measuring CR+PR rates per Lugano criteria (BICR-assessed) and duration of response (DOR, 26 months) tracking time from initial response to progression/death.
Experiment 8 Reporting the Activity Date of This ADC					[8]
Patients Enrolled	Eligible patients have untreated PET-positive DLBCL (Lugano 4-5), ECOG 0-2, and adequate cardiac/organ function; HIV/HBV/HCV control is required if applicable. Exclusions: transformed DLBCL, PMBCL, Stage I disease, active CVD/neuropathy (>Grade 1), CNS involvement, uncontrolled infections/autoimmunity, or concurrent malignancies within 2 years. Live vaccines and allogeneic transplants are prohibited.    Click to Show/Hide
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT06717347	Clinical Status	PHASE3
Clinical Description	A Randomized, Open-Label, Multicenter, Phase 3 Study of Zilovertamab Vedotin (MK-2140) in Combination With R-CHP Versus R-CHOP in Participants With Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL) (waveLINE-010)
Primary Endpoint	Primary endpoints include PFS (50 months, time from randomization to progression/death per Lugano/BICR) and CR at EOT (32 months, BICR-assessed complete response excluding early discontinuations). Secondary efficacy measures comprise OS (74 months), EFS (74 months, covering progression/recurrence/second malignancy/death), and DurCR (74 months, sustained CR until progression/death).    Click to Show/Hide
Other Endpoint	Safety assessments track AE incidence (9 months) and treatment discontinuations due to AEs (6 months). HRQoL is evaluated via FACT-Lym (Week 25 vs. baseline), measuring physical, emotional, functional, and lymphoma-specific domains (0-168 scale, higher=better), alongside neurotoxicity using FACT/GOG-NTX (0-44 scale for sensory/motor symptoms).
Experiment 9 Reporting the Activity Date of This ADC					[9]
Patients Enrolled	Eligible patients must have confirmed B-ALL, DLBCL/Burkitt lymphoma, neuroblastoma, or Ewing sarcoma per WHO/histologic criteria. Exclusions: solid organ transplants, active cardiovascular disease (e.g., arrhythmias, cirrhosis), neuropathy (>Grade 1), Down syndrome, GVHD, HIV/HBV/HCV, or recent cytotoxic/CYP3A4-modulating therapies. Prohibited: live vaccines (30 days prior), chronic steroids (>10mg prednisone/day), unresolved post-surgical complications, or concurrent malignancies requiring treatment. Prior radiotherapy/systemic therapy requires washout (4 weeks).    Click to Show/Hide
Administration Dosage	Participants receive escalating doses of zilovertamab vedotin via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks).
Related Clinical Trial
NCT Number	NCT06395103	Clinical Status	PHASE1|||PHASE2
Clinical Description	LIGHTBEAM-U01 Substudy 01A: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors
Primary Endpoint	The primary objectives assess safety and efficacy in pediatric patients (aged 1-18 years). Part 1 evaluates dose-limiting toxicities (DLTs) within 42 days and tracks adverse events (AEs), treatment discontinuations, and dose modifications over 60 months. Efficacy endpoints include objective response rates (ORR) per disease-specific criteria: CR/CRi for B-ALL (Ponte-di-Legno) and CR/PR for DLBCL/Burkitt lymphoma (IPNHL), neuroblastoma (INRC), and Ewing sarcoma (RECIST 1.1). Key secondary measures include duration of response (DOR) and rates of subsequent SCT or CAR-T therapy.    Click to Show/Hide
Other Endpoint	Pharmacokinetic analyses measure exposure (AUC), peak/trough concentrations (Cmax/Ctrough), and half-life (t1/2) for total antibody, ADC, and MMAE across cycles (21-day intervals) over 60 months. Immunogenicity is assessed via antidrug antibody (ADA) incidence. Part 2 monitors AE-related outcomes (incidence, discontinuations, dose modifications) alongside efficacy metrics. Treatment impact is further characterized by post-therapy SCT/CAR-T utilization rates.    Click to Show/Hide
Experiment 10 Reporting the Activity Date of This ADC					[10]
Patients Enrolled	Participants were required to provide tumor tissue, demonstrate negative or controlled HIV/hepatitis status, complete prior therapies, and adhere to contraception protocols, with stringent monitoring of pharmacokinetic profiles across specified timepoints in 21-day cycles.
Administration Dosage	Participants will receive intravenous (IV) zilovertamab vedotin 2.5 mg/kg on Day 1 of each repeated 21-day cycle (Q1/3W) or 1.75 mg/kg on Day 1 and Day 8 of each 21-day cycle (Q2/3W). Treatment will continue until progressive disease or discontinuation
Related Clinical Trial
NCT Number	NCT04504916	Clinical Status	PHASE2
Clinical Description	A Phase 2 Study of VLS-101 in Patients With Solid Tumors
Primary Endpoint	Efficacy endpoints included Objective Response Rate (ORR) assessed by both Blinded Independent Central Review (BICR) and investigators per RECIST v1.1, with key measures like Time to Response (TTR), Duration of Response (DOR), Progression-Free Survival (PFS), Time to Treatment Failure (TTF), and Overall Survival (OS) tracked over ~30 months. Safety assessments involved monitoring Adverse Events (AEs), treatment discontinuations due to AEs, and pharmacokinetic parameters (Cmax, AUC) for zilovertamab vedotin, total antibody, and MMAE under Q1/3W and Q2/3W dosing schedules.    Click to Show/Hide
Other Endpoint	The study enrolled patients with metastatic solid tumors (TNBC, HER2-negative breast cancer, NSCLC, gastric, pancreatic, or platinum-resistant ovarian cancer) who progressed after prior therapy, had measurable disease, and adequate organ function. Key exclusions included Grade >1 neuropathy, CNS malignancies, other major cancers, uncontrolled infections, cardiovascular disease, liver cirrhosis, pregnancy, recent major surgery, MMAE intolerance, or concurrent trial participation.    Click to Show/Hide
Experiment 11 Reporting the Activity Date of This ADC					[10]
Patients Enrolled	Eligible participants had histologically confirmed locally advanced/unresectable or metastatic urothelial cancer (mUC), refractory to PD-1/L1 therapy, with available tumor biopsy for biomarker analysis. Key exclusions included other active malignancies, recent systemic therapy (within 4 weeks), active infections requiring treatment, recent live vaccines (within 30 days), and HIV/hepatitis B/C infections.    Click to Show/Hide
Administration Dosage	Participants will receive zilovertamab vedotin 2mg/kg administered on Day 1 and Day 8 of each 3 week cycle (Q3W) until documented disease progression or any other discontinuation criterion is met.
Related Clinical Trial
NCT Number	NCT05562830	Clinical Status	PHASE1|||PHASE2
Clinical Description	A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants With PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A
Primary Endpoint	The safety and efficacy endpoints involved tracking adverse events (AEs) over ~5 years, including discontinuation rates due to AEs, while efficacy was assessed via Objective Response Rate (ORR) using RECIST 1.1 criteria (CR: disappearance of all target lesions; PR: ≥30% decrease in sum of lesion diameters) over ~2 years, with results reviewed by Blinded Independent Central Review (BICR).    Click to Show/Hide
Other Endpoint	Duration of Response (DOR) was evaluated over ~2 years, measuring the time from first confirmed CR/PR (per RECIST 1.1) until progressive disease (PD: ≥20% increase in lesion diameters with ≥5 mm absolute growth or new lesions) or death, with assessments confirmed by BICR.
Experiment 12 Reporting the Activity Date of This ADC					[11]
Efficacy Data	Objective Response Rate (ORR)	30%
Patients Enrolled	Patients with diffuse large B-cell lymphoma (DLBCL), PET-positive disease, and ECOG PS of 0-2. Pts must have received 2 prior lines of therapy.
Administration Dosage	2.50 mg/kg IV Q3W.
Related Clinical Trial
NCT Number	NCT05144841	Clinical Status	Phase 2
Clinical Description	A phase 2 open-label clinical study to evaluate the efficacy and safety of zilovertamab vedotin (MK-2140) in participants with relapsed or refractory diffuse large B-cell lymphoma (waveline-004).
Experiment 13 Reporting the Activity Date of This ADC					[12]
Efficacy Data	Objective Response Rate (ORR)	47.00 60.00 %
Patients Enrolled	Patients with tumor histologies of mantle cell lymphoma (MCL), chronic lymphocytic leukemia, diffuse large B-cell lymphoma (DLBCL). Patients had received a median of four previous drug and/or cellular therapies.
Administration Dosage	2.50 mg/kg every 3 week.
Related Clinical Trial
NCT Number	NCT03833180	Clinical Status	Phase 1
Clinical Description	A phase 1 dose-escalation and cohort-expansion study of VLS-101 in subjects with hematological malignancies (waveline-001).
Experiment 14 Reporting the Activity Date of This ADC					[13]
Patients Enrolled	Patients with diffuse large B-cell lymphoma (DLBCL) after 1 line of prior therapy (cohort A) or 2 lines of prior therapy (cohort B).
Administration Dosage	ZV (1.50, 1.75, 2.00, 2.25, and 2.50 mg/kg) with gemcitabine-oxaliplatin + rituximab (R-GemOx).
Related Clinical Trial
NCT Number	NCT05139017	Clinical Status	Phase 2/3
Clinical Description	A phase 2/3 multicenter, open-label, randomized, active-control study of zilovertamab vedotin (MK-2140) in combination with standard of care in participants with relapsed or refractory diffuse large B-cell lymphoma (waveline-003).
Experiment 15 Reporting the Activity Date of This ADC					[14]
Patients Enrolled	Patients with mantle cell lymphoma (MCL), Richter's transformation (RT), chronic lymphocytic leukemia (CLL), or follicular lymphoma (FL), relapsed or refractory (R/R) disease, ECOG performance status of 0 to 2.
Administration Dosage	ZV 2.0 to 2.50 mg/kg IV Q3W.
Related Clinical Trial
NCT Number	NCT05458297	Clinical Status	Phase 2
Clinical Description	A multicenter, open-label, phase 2 basket study to evaluate the safety and efficacy of MK-2140 as a monotherapy and in combination in participants with aggressive and indolent B-cell malignancies.
Experiment 16 Reporting the Activity Date of This ADC					[15]
Patients Enrolled	Patients with previously untreated histologically confirmed diffuse large B-cell lymphoma (DLBCL), PET-positive and ECOG PS of 0 or 1.
Administration Dosage	ZV was 1.75 mg/kg (modified to 1.50, 2.00, 2.25, or 2.50 mg/kg) administered as an intravenous infusion every 3 weeks (Q3W) in combination with R-CHP.
Related Clinical Trial
NCT Number	NCT05406401	Clinical Status	Phase 2
Clinical Description	A multicenter, open-label, phase 2 dose escalation and confirmation, and efficacy expansion study of zilovertamab vedotin (MK-2140) in combination with r-chp in participants with DLBCL (waveline).
Experiment 17 Reporting the Activity Date of This ADC					[16]
Patients Enrolled	Patients with locally advanced or metastatic urothelial carcinoma (mUC) whose disease is resistant to treatment with programmed cell death-1/ligand 1 (PD-1/L1) inhibitors.
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT05562830	Clinical Status	Phase 1/2
Clinical Description	A phase 1/2 open-label rolling-arm umbrella platform study of investigational agents with or without pembrolizumab in participants with PD-1/L1 refractory locally advanced or metastatic urothelial carcinoma (keymaker-u04): substudy 04a.
Experiment 18 Reporting the Activity Date of This ADC					[17]
Related Clinical Trial
NCT Number	NCT04504916	Clinical Status	Phase 1
Clinical Description	A phase 2 study of VLS-101 in patients with solid tumors.

Experiment 1 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 0%	Negative ROR1 expression (ROR1-)
Method Description	VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 5 mg/kg.
In Vivo Model	Richter syndrome PDX model (PDX: RS9737)
Experiment 2 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 0%	Negative ROR1 expression (ROR1-)
Method Description	VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 2.5 mg/kg.
In Vivo Model	Richter syndrome PDX model (PDX: RS9737)
Experiment 3 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 88.80%	High ROR1 expression (ROR1+++)
Method Description	VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 2.5 mg/kg.
In Vivo Model	Richter syndrome PDX model (PDX: IP867/17)
Experiment 4 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 90.90%	Moderate ROR1 expression (ROR1++)
Method Description	VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 2.5 mg/kg.
In Vivo Model	Richter syndrome PDX model (PDX: RS9737)
Experiment 5 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Moderate ROR1 expression (ROR1++)
Method Description	VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 5 mg/kg.
In Vivo Model	Richter syndrome PDX model (PDX: RS9737)
Experiment 6 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	High ROR1 expression (ROR1+++)
Method Description	VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 5 mg/kg.
In Vivo Model	Richter syndrome PDX model (PDX: RS9737)
Experiment 7 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	High ROR1 expression (ROR1+++)
Method Description	VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 2.5 mg/kg.
In Vivo Model	Richter syndrome PDX model (PDX: RS9737)
Experiment 8 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	High ROR1 expression (ROR1+++)
Method Description	VLS-101 induces efficient tumor cell killing in cell line-derived models of IP867/17 and RS1316 cells with UC-961 expression with high expression. After palpable tumors were evident (tumor volume of 0.2 cm3),animals were randomly assigned to vehicle,VLS 101 5 mg/kg.
In Vivo Model	Richter syndrome PDX model (PDX: IP867/17)

Ref 1	A Sequential Population Pharmacokinetic Model of Zilovertamab Vedotin in Patients with Hematologic Malignancies Extrapolated to the Pediatric Population
Ref 2	Zilovertamab Vedotin Targeting of ROR1 as Therapy for Lymphoid Cancers
Ref 3	A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)
Ref 4	A Study to Evaluate Zilovertamab Vedotin (MK-2140) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-004)
Ref 5	A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Hematologic Malignancies (MK-2140-001)
Ref 6	A Study of Zilovertamab Vedotin (MK-2140) in Combination With Cyclophosphamide, Doxorubicin, and Prednisone Plus Rituximab or Rituximab Biosimilar (Truxima) (R-CHP) in Participants With Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-007)
Ref 7	A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)
Ref 8	A Study to Evaluate Zilovertamab Vedotin (MK-2140) Combination With Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Previously Untreated DLBCL (MK-2140-010)
Ref 9	Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)
Ref 10	A Substudy of Investigational Agents in Programmed Cell Death-1/Ligand 1 (PD-1/L1) Refractory Locally Advanced or Metastatic Urothelial Carcinoma (mUC) (MK-3475-04A)
Ref 11	Open-label, active-control, phase 2/3 study of zilovertamab vedotin plus standard of care in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2022 40:16_suppl, TPS7592-TPS7592.
Ref 12	Phase 2 study of zilovertamab vedotin (ZV) in combination with cyclophosphamide, doxorubicin, and prednisone plus rituximab (R-CHP) in previously untreated diffuse large B-cell lymphoma (DLBCL). J Clin Oncol. 2023 41:16_suppl, TPS7589-TPS7589.
Ref 13	A phase I study of CPI-0610, a bromodomain and extra terminal protein (BET) inhibitor in patients with relapsed or refractory lymphoma. Ann. Oncol. 2018 Mar; 29(3):Supplement I117.
Ref 14	BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic solid tumor: Results from a first-in-human phase 1 study. J Clin Oncol. 2023 41:16_suppl, 3001-3001.
Ref 15	A phase 2 study of the safety and efficacy of zilovertamab vedotin as monotherapy or in combination in patients (pts) with aggressive and indolent B-cell malignancies. J Clin Oncol. 2023 41:16_suppl, TPS7595-TPS7595.
Ref 16	A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants With PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A, NCT05562830
Ref 17	A Phase 2 Study of VLS-101 in Patients With Solid Tumors, NCT04504916
Ref 18	ROR1 targeting with the antibody-drug conjugate VLS-101 is effective in Richter syndrome patient-derived xenograft mouse models. Blood. 2021 Jun 17;137(24):3365-3377.