ADC Name	BB-1701
Synonyms	BB-1701    Click to Show/Hide
Organization	Bliss Biopharmaceutical (BlissBio) (Originator);Eisai (No Rights)
Drug Status	Phase 2
Drug-to-Antibody Ratio	4
Structure
	3D MOL			2D MOL
Antibody Name	Anti-HER2 antibody					Antibody Info
Antigen Name	Receptor tyrosine-protein kinase erbB-2 (HER2)					Antigen Info
Payload Name	Eribulin					Payload Info
Payload Target	Microtubule (MT)					Target Info
Linker Name	Mal-PEG2-Val-Cit-PABC					Linker Info
Conjugate Type	Random Cysteines
Combination Type	ecteribulin

Bystander Killing Effect	Description	Reference
yes	The bystander effect of BB-1701 was investigated in both in vitro and in vivo settings. In an in vitro cytotoxicity assay, NCI-N87 (HER2 high) cells and U87MG (HER2 null) cells were treated with BB-1701 and controls. BB-1701 was highly effective at suppressing N87 cell growth, with an IC50 of approximately 0.1 nM, but was totally ineffective at suppressing U87 cell growth, although U87 itself was quite sensitive to eribulin (IC50 ~ 0.02 nM, ). However, when the two cell lines were treated with BB-1701 in a coculture, there was a significant cytotoxicity at low drug concentrations, with an IC50 of approximately 0.28 nM    Click to Show/Hide	[1]

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	65.485	ug/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 2 mg/kg ,Male	[1]
Area Under the Concentration-Time Curve (AUC)	12406.315	ug·h/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 2 mg/kg, Male, AUC0-154h.	[1]
Maximum Observed Concentration (Cmax)	63.91	ug/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 2 mg/kg ,female	[1]
Area Under the Concentration-Time Curve (AUC)	12827.924	ug·h/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 2 mg/kg, female, AUC0-154h.	[1]
Maximum Observed Concentration (Cmax)	97.01	ug/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 4 mg/kg ,Male	[1]
Area Under the Concentration-Time Curve (AUC)	24699.408	ug·h/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 4 mg/kg, Male, AUC0-154h.	[1]
Maximum Observed Concentration (Cmax)	101.952	ug/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 4 mg/kg ,female	[1]
Area Under the Concentration-Time Curve (AUC)	20658.105	ug·h/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 4 mg/kg, female, AUC0-154h.	[1]
Maximum Observed Concentration (Cmax)	265.021	ug/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 8 mg/kg ,Male	[1]
Area Under the Concentration-Time Curve (AUC)	55919.672	ug·h/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 8 mg/kg, Male, AUC0-154h.	[1]
Maximum Observed Concentration (Cmax)	248.328	ug/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 8 mg/kg ,female	[1]
Area Under the Concentration-Time Curve (AUC)	59691.963	ug·h/mL	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 8 mg/kg, female, AUC0-154h.	[1]

Standard Type	Value	Units	Description	Reference
Elimination Half-Life (t1/2)	119.272	h	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 2 mg/kg ,Male	[1]
Elimination Half-Life (t1/2)	132.225	h	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 2 mg/kg ,female	[1]
Elimination Half-Life (t1/2)	166.717	h	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 4 mg/kg ,Male	[1]
Elimination Half-Life (t1/2)	111.512	h	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 4 mg/kg ,female	[1]
Elimination Half-Life (t1/2)	192.134	h	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 8 mg/kg ,Male	[1]
Elimination Half-Life (t1/2)	160.989	h	Serum pharmacokinetic parameters of ADC after administration of BB-1701 in cynomolgus monkeys, 8 mg/kg ,female	[1]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Objective Response Rate (ORR)	NCT04257110	PHASE1	A First-in-human, Open Label, Multiple Dose, Dose Escalation and Cohort Expansion Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of BB-1701 in Subjects With Locally Advanced/Metastatic HER2 Expressing Solid Tumors    Click to Show/Hide
Disease control rate (DCR)	NCT04257110	PHASE1	A First-in-human, Open Label, Multiple Dose, Dose Escalation and Cohort Expansion Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of BB-1701 in Subjects With Locally Advanced/Metastatic HER2 Expressing Solid Tumors    Click to Show/Hide
Undisclosed	NCT06188559	PHASE2	An Open-label, Multicenter, Phase 2 Dose Optimization and Expansion Study to Evaluate the Safety and Efficacy of BB-1701, an Anti-human Epidermal Growth Factor Receptor 2 (Anti-HER2) Antibody-drug Conjugate (ADC), in Previously Treated Subjects With HER2-positive or HER2-low Unresectable or Metastatic Breast Cancer    Click to Show/Hide
Objective Response Rate (ORR)	NCT04257110	Phase 1	A first-in-human, open label, multiple dose, dose escalation and cohort expansion phase 1 study to investigate the safety, tolerability, pharmacokinetics and antitumor activities of bb-1701 in subjects with locally advanced/metastatic HER2 expressing solid tumors.    Click to Show/Hide

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Objective Response Rate (ORR)	30%
Patients Enrolled	Key eligibility: Adults (≥18) with advanced/metastatic HER2+ tumors (measurable per RECIST 1.1), ECOG 0-1, life expectancy ≥12 weeks. Major exclusions: active CNS metastases requiring steroids (>10mg prednisone), Grade ≥2 peripheral neuropathy, QTcF >450/470ms (M/F), active ILD/pneumonitis, HIV/HBV/HCV infections, or prior cumulative doxorubicin >360mg/m2. Fresh tumor tissue required for HER2 confirmation.    Click to Show/Hide
Administration Dosage	BB-1701 will be administered as an intravenous infusion, every 3 weeks or every 4 weeks or every 6 weeks.
Related Clinical Trial
NCT Number	NCT04257110	Clinical Status	PHASE1
Clinical Description	A First-in-human, Open Label, Multiple Dose, Dose Escalation and Cohort Expansion Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of BB-1701 in Subjects With Locally Advanced/Metastatic HER2 Expressing Solid Tumors
Primary Endpoint	Primary endpoints include safety evaluation (AEs, SAEs, DLTs) and MTD determination during Cycle 1 (21-day cycles) in HER2-expressing solid tumor patients, with monitoring continuing for up to 2 years to assess BB-1701's safety profile.
Other Endpoint	Secondary objectives comprise PK characterization (AUC0-inf, Cmax), immunogenicity assessment (ADA incidence), and preliminary anti-tumor activity evaluation (ORR, PFS, DOR) through serial tumor assessments per RECIST 1.1 for up to 2 years.
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Disease control rate (DCR)	60%
Patients Enrolled	Key eligibility: Adults (≥18) with advanced/metastatic HER2+ tumors (measurable per RECIST 1.1), ECOG 0-1, life expectancy ≥12 weeks. Major exclusions: active CNS metastases requiring steroids (>10mg prednisone), Grade ≥2 peripheral neuropathy, QTcF >450/470ms (M/F), active ILD/pneumonitis, HIV/HBV/HCV infections, or prior cumulative doxorubicin >360mg/m2. Fresh tumor tissue required for HER2 confirmation.    Click to Show/Hide
Administration Dosage	BB-1701 will be administered as an intravenous infusion, every 3 weeks or every 4 weeks or every 6 weeks.
Related Clinical Trial
NCT Number	NCT04257110	Clinical Status	PHASE1
Clinical Description	A First-in-human, Open Label, Multiple Dose, Dose Escalation and Cohort Expansion Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of BB-1701 in Subjects With Locally Advanced/Metastatic HER2 Expressing Solid Tumors
Primary Endpoint	Primary endpoints include safety evaluation (AEs, SAEs, DLTs) and MTD determination during Cycle 1 (21-day cycles) in HER2-expressing solid tumor patients, with monitoring continuing for up to 2 years to assess BB-1701's safety profile.
Other Endpoint	Secondary objectives comprise PK characterization (AUC0-inf, Cmax), immunogenicity assessment (ADA incidence), and preliminary anti-tumor activity evaluation (ORR, PFS, DOR) through serial tumor assessments per RECIST 1.1 for up to 2 years.
Experiment 3 Reporting the Activity Date of This ADC					[3]
Patients Enrolled	Key eligibility: Adults (&ge;18) with HER2-positive/HER2-low metastatic BC (1-3 prior chemo regimens, T-DXd exposed), measurable disease (RECIST 1.1), ECOG 0-1. Major exclusions: active CNS metastases, prior eribulin, Grade &ge;2 peripheral neuropathy/ILD, QTcF >470ms, uncontrolled infections (HIV/HBV/HCV exceptions), or LVEF <50%. Tumor tissue must be available for central HER2 confirmation.    Click to Show/Hide
Administration Dosage	BB-1701 will be administered as an intravenous infusion, every 3 weeks (21-day cycle).
Related Clinical Trial
NCT Number	NCT06188559	Clinical Status	PHASE2
Clinical Description	An Open-label, Multicenter, Phase 2 Dose Optimization and Expansion Study to Evaluate the Safety and Efficacy of BB-1701, an Anti-human Epidermal Growth Factor Receptor 2 (Anti-HER2) Antibody-drug Conjugate (ADC), in Previously Treated Subjects With HER2-positive or HER2-low Unresectable or Metastatic Breast Cancer
Primary Endpoint	Primary endpoints include comprehensive safety evaluation (AEs, lab abnormalities, vital signs, ECGs, ECOG status) during dose optimization (Part 1, 35 months) and ORR assessment by investigator (Part 1) or BICR (Part 2) per RECIST v1.1 in HER2-positive/HER2-low metastatic breast cancer patients previously treated with T-DXd.
Other Endpoint	Secondary objectives encompass efficacy measures (DOR, PFS, OS, DCR, CBR, TTR) and detailed PK analysis (Cmax, Tmax, AUC, t1/2, CL, Vss, Ctrough) of BB-1701 components in both parts (35 months), with Part 2 featuring BICR-confirmed assessments and additional safety monitoring identical to Part 1.
Experiment 4 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Objective Response Rate (ORR)	50.00 70.60 %
Patients Enrolled	Patients with advanced/metastatic HER2-positive solid tumors, who had progressed on, or were intolerant to prior standard therapies, with ECOG PS 2, and measurable disease,.
Administration Dosage	6 dose levels from 0.40 to 2.60 mg/kg Q3W.
Related Clinical Trial
NCT Number	NCT04257110	Clinical Status	Phase 1
Clinical Description	A first-in-human, open label, multiple dose, dose escalation and cohort expansion phase 1 study to investigate the safety, tolerability, pharmacokinetics and antitumor activities of bb-1701 in subjects with locally advanced/metastatic HER2 expressing solid tumors.

Ref 1	Preclinical studies of BB-1701, a HER2-targeting eribulin-containing ADC with potent bystander effect and ICD activity
Ref 2	A First-in-human Study of Multiple Doses of BB-1701 in Subjects With Locally Advanced/Metastatic HER2 Expressing Solid Tumors
Ref 3	A Study of BB-1701 in Previously Treated Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive or HER2-low Unresectable or Metastatic Breast Cancer
Ref 4	A first in-human, multicenter, open-label, dose-finding phase 1 study of the immune stimulator antibody conjugate NJH395 in patients with nonbreast HER2+ advanced malignancies. J Immunother. Cancer 2020 Volume 8:Suppl 3.