Payload Information

General Information of This Payload
Payload ID
PAY0EQOWS
Name
Duostatin 5
Synonyms
Duostatin 5; CE421MMY47; 2124210-34-8; UNII-CE421MMY47; DUO-5; SCHEMBL20846018; EX-A5872; HY-145149; CS-0356744
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Target Microtubule (MT)
 Target Info 
Structure
Formula
C40H69N9O6
Isosmiles
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=C(C=C2)N)CN=[N+]=[N-])OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C
PubChem CID
138320017
InChI
InChI=1S/C40H69N9O6/c1-13-26(6)36(48(10)40(53)34(24(2)3)45-39(52)35(25(4)5)47(8)9)32(54-11)22-33(50)49-20-14-15-31(49)37(55-12)27(7)38(51)44-30(23-43-46-42)21-28-16-18-29(41)19-17-28/h16-19,24-27,30-32,34-37H,13-15,20-23,41H2,1-12H3,(H,44,51)(H,45,52)/t26-,27+,30-,31-,32+,34-,35-,36-,37+/m0/s1
InChIKey
QIHHTRNUHMRKQK-MNFMTBGBSA-N
IUPAC Name
(2S)-N-[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(2S)-1-(4-aminophenyl)-3-azidopropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N,3-dimethylbutanamide
Pharmaceutical Properties
Molecule Weight
772
Polar area
161
Complexity
1270
xlogp Value
5.5
Heavy Count
55
Rot Bonds
22
Hbond acc
10
Hbond Donor
3
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
AMT-151 [Phase 1]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Patients Enrolled
Eligible patients (≥18 years) must have advanced ovarian, endometrial, lung, breast, pancreatic, or mesothelioma cancers that progressed after prior therapies, with measurable/non-measurable disease per RECIST 1.1, ECOG 0-1, and adequate organ function. Exclusions include prior Folate Receptor Alpha-targeted therapy, active CNS metastases, unresolved toxicities (>Grade 1), recent anticancer therapies/radiotherapy/surgery, transplant history, or significant comorbidities. WCBP require negative pregnancy tests.

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Related Clinical Trial
NCT Number NCT05498597  Phase Status PHASE1
Clinical Description
First-in-Human, Phase 1 Study of AMT-151, an Anti-Folate Receptor Alpha Antibody-Drug Conjugate, in Patients With Selected Advanced Solid Tumours
Primary Endpoint
The study evaluates the Recommended Phase 2 Dose (RP2D) and Maximum Tolerated Dose (MTD) based on dose-limiting toxicities (DLTs) over 24 months, alongside assessing safety through incidence of adverse events graded by CTCAE v5.0.
Other Endpoint
Efficacy outcomes include Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-Free Survival (PFS), Time to Treatment Response (TTR), Duration of Response (DoR), and Overall Survival (OS), along with pharmacokinetic parameters (Cmax, AUC, t1/2, Tmax) and anti-drug antibody (ADA) concentrations, all measured over 24 months.
Experiment 2 Reporting the Activity Date of This ADC [2]
Related Clinical Trial
NCT Number NCT05498597  Phase Status Phase 1
Clinical Description
First-in-human, phase 1 study of AMT-151, an anti-folate receptor alpha antibody-drug conjugate, in patients with selected advanced solid tumours.
Trastuzumab botidotin [Approved in 2025]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 10 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data stable disease (SD)
33%
Patients Enrolled
Eligibility requires adults (≥18) with incurable HER2+ (IHC≥1+/ISH/NGS-confirmed) malignancies who exhausted standard therapies, with adequate hematologic/organ function (ANC≥1500/uL, CrCl≥50mL/min, LVEF≥45%), excluding those with cardiac dysfunction (NYHA III-IV, QTc>470ms), active hepatitis/HIV, uncontrolled comorbidities, prior trastuzumab intolerance, or symptomatic brain metastases. Fertile patients must use contraception for 7 months post-treatment.

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Administration Dosage
Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
Related Clinical Trial
NCT Number NCT03602079  Phase Status PHASE1|||PHASE2
Clinical Description
A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies
Primary Endpoint
The phase I primary endpoint evaluates maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) in HER2-positive advanced cancer patients over a 21-day DLT observation period, with continuous safety monitoring up to 24 months.
Other Endpoint
Secondary phase I objectives include comprehensive safety assessment (CTCAE v4.03 graded AEs, immunogenicity via anti-drug antibodies) and pharmacokinetic profiling (Cmax, CL, AUC, hale-life, Vz, Vss) through 84-day PK sampling in this dose-escalation study.
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data progressive disease (PD)
41%
Patients Enrolled
Eligibility requires adults (≥18) with incurable HER2+ (IHC≥1+/ISH/NGS-confirmed) malignancies who exhausted standard therapies, with adequate hematologic/organ function (ANC≥1500/uL, CrCl≥50mL/min, LVEF≥45%), excluding those with cardiac dysfunction (NYHA III-IV, QTc>470ms), active hepatitis/HIV, uncontrolled comorbidities, prior trastuzumab intolerance, or symptomatic brain metastases. Fertile patients must use contraception for 7 months post-treatment.

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Administration Dosage
Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
Related Clinical Trial
NCT Number NCT03602079  Phase Status PHASE1|||PHASE2
Clinical Description
A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies
Primary Endpoint
The phase I primary endpoint evaluates maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) in HER2-positive advanced cancer patients over a 21-day DLT observation period, with continuous safety monitoring up to 24 months.
Other Endpoint
Secondary phase I objectives include comprehensive safety assessment (CTCAE v4.03 graded AEs, immunogenicity via anti-drug antibodies) and pharmacokinetic profiling (Cmax, CL, AUC, hale-life, Vz, Vss) through 84-day PK sampling in this dose-escalation study.
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Partial Response (PR)
26%
Patients Enrolled
Eligibility requires adults (≥18) with incurable HER2+ (IHC≥1+/ISH/NGS-confirmed) malignancies who exhausted standard therapies, with adequate hematologic/organ function (ANC≥1500/uL, CrCl≥50mL/min, LVEF≥45%), excluding those with cardiac dysfunction (NYHA III-IV, QTc>470ms), active hepatitis/HIV, uncontrolled comorbidities, prior trastuzumab intolerance, or symptomatic brain metastases. Fertile patients must use contraception for 7 months post-treatment.

   Click to Show/Hide
Administration Dosage
Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
Related Clinical Trial
NCT Number NCT03602079  Phase Status PHASE1|||PHASE2
Clinical Description
A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies
Primary Endpoint
The phase I primary endpoint evaluates maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) in HER2-positive advanced cancer patients over a 21-day DLT observation period, with continuous safety monitoring up to 24 months.
Other Endpoint
Secondary phase I objectives include comprehensive safety assessment (CTCAE v4.03 graded AEs, immunogenicity via anti-drug antibodies) and pharmacokinetic profiling (Cmax, CL, AUC, hale-life, Vz, Vss) through 84-day PK sampling in this dose-escalation study.
Experiment 4 Reporting the Activity Date of This ADC [3]
Efficacy Data Disease control rate (DCR)
59%
Patients Enrolled
Eligibility requires adults (≥18) with incurable HER2+ (IHC≥1+/ISH/NGS-confirmed) malignancies who exhausted standard therapies, with adequate hematologic/organ function (ANC≥1500/uL, CrCl≥50mL/min, LVEF≥45%), excluding those with cardiac dysfunction (NYHA III-IV, QTc>470ms), active hepatitis/HIV, uncontrolled comorbidities, prior trastuzumab intolerance, or symptomatic brain metastases. Fertile patients must use contraception for 7 months post-treatment.

   Click to Show/Hide
Administration Dosage
Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
Related Clinical Trial
NCT Number NCT03602079  Phase Status PHASE1|||PHASE2
Clinical Description
A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies
Primary Endpoint
The phase I primary endpoint evaluates maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) in HER2-positive advanced cancer patients over a 21-day DLT observation period, with continuous safety monitoring up to 24 months.
Other Endpoint
Secondary phase I objectives include comprehensive safety assessment (CTCAE v4.03 graded AEs, immunogenicity via anti-drug antibodies) and pharmacokinetic profiling (Cmax, CL, AUC, hale-life, Vz, Vss) through 84-day PK sampling in this dose-escalation study.
Experiment 5 Reporting the Activity Date of This ADC [4]
Patients Enrolled
Eligibility requires adults (≥18) with incurable HER2+ (IHC≥1+/ISH/NGS-confirmed) solid tumors who have exhausted standard therapies, with adequate organ function and ECOG 0-1.
Administration Dosage
According to the initial dose, the highest dose and the modified Fibonacci method, the dose escalation of A166 for injection is designed as: 0.1 mg/kg, 0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg, 4.8 mg/kg (the highest dose is tentatively set at 4.8 mg/kg).
Related Clinical Trial
NCT Number NCT05311397  Phase Status PHASE1
Clinical Description
A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of A166 in Patients With Unresectable, Locally Advanced or Metastatic HER2-expressing Solid Tumors (KL166-I-01-CTP)
Primary Endpoint
Primary endpoint evaluates investigator-assessed ORR (CR+PR) per RECIST v1.1 criteria in HER2-positive advanced solid tumor patients over 24 months.
Other Endpoint
Secondary endpoints include 24-month assessments of DOR (from first response to PD/death), PFS (from randomization to PD/death), and OS (from randomization to death/loss to follow-up), all measured according to RECIST v1.1 standards.
Experiment 6 Reporting the Activity Date of This ADC [5]
Patients Enrolled
Eligibility includes adults (18-75y) with confirmed HER2+ (IHC3+ or IHC2+/FISH+) metastatic breast cancer and prior taxane exposure, excluding those with cardiac dysfunction (NYHA III-IV/QTc prolongation), active ILD, uncontrolled CNS metastases, or trastuzumab intolerance, while requiring adequate organ function for safety evaluation.
Administration Dosage
4.8 mg/kg for each 21 day cycle
Related Clinical Trial
NCT Number NCT05346328  Phase Status PHASE2
Clinical Description
An Open-clinical Trial Phase II, Injection of A166 for HER2-positive Patients With Refractory Unresectable Locally Advanced or Metastatic Breast Cancer;KL166-IIS-001
Primary Endpoint
The primary endpoint evaluates ORR (complete/partial response rates per RECIST 1.1) in HER2-positive metastatic breast cancer patients over 24 months, focusing on heavily pretreated populations who failed ≥3 prior HER2-targeted therapies including trastuzumab, TKIs, and ADCs.
Other Endpoint
Secondary objectives assess 24-month efficacy through PFS (first dose to progression/death), DCR/CRB (response+stable disease), DOR (response duration), TTR (time to progression excluding deaths), and OS (overall survival from first dose), all measured by RECIST 1.1 standards in this refractory patient population.
Experiment 7 Reporting the Activity Date of This ADC [6]
Efficacy Data Partial Response (PR)
25.92%
Patients Enrolled
Locally advanced/metastatic solid tumors expressing human epidermal growth factor receptor 2 (HER2) or are HER2 amplified.
Administration Dosage
0.30, 1.20, 3.60, 4.80 mg/kg, every 3 weeks from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
Related Clinical Trial
NCT Number NCT03602079  Phase Status Phase 1
Clinical Description
A phase 1-2, FIH Study of A166 in locally advanced/metastatic solid tumors expressing human epidermal growth factor receptor 2 (HER2) or are HER2 amplified that did not respond or stopped responding to approved therapies.
Primary Endpoint
Overall incidence of ophthalmic toxicities in the 3.60 mg/kg cohort was 80% and in the 4.80 mg/kg cohort it was 83.00%. Responses were seen only at the dose levels of 3.60 mg/kg and 4.80 mg/kg. Among the 27 patients evaluable for efficacy,best response was progression of disease in 11 patients (40.74%), stable disease in 9 patients (33.33%) and partial response in 7 patients (25.92%),for the total disease control rate of 59%.

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Experiment 8 Reporting the Activity Date of This ADC [7]
Efficacy Data Objective Response Rate (ORR)
73.90
68.60 %
Patients Enrolled
Patients with HER2-expressing advanced solid tumours.
Administration Dosage
0.10, 0.30, 0.60, 1.20, 2.40, 3.60, 4.80 or 6.00 mg/kg Q3W.
Related Clinical Trial
NCT Number NCT05311397  Phase Status Phase 1
Clinical Description
A phase 1 study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of A166 in patients with unresectable, locally advanced or metastatic HER2-expressing solid tumors (KL166-I-01-CTP).
Experiment 9 Reporting the Activity Date of This ADC [8]
Related Clinical Trial
NCT Number NCT05346328  Phase Status Phase 2
Clinical Description
An open-clinical trial phase , injection of A166 for HER2-positive patients with refractory unresectable locally advanced or metastatic breast cancer KL166-2S-001.
Experiment 10 Reporting the Activity Date of This ADC [9]
Related Clinical Trial
NCT Number NCT03602079  Phase Status Phase 1/2
Clinical Description
A phase 1-2, FIH study of A166 in locally advanced/metastatic solid tumors expressing human epidermal growth factor receptor 2 (HER2) or are HER2 amplified that did not respond or stopped responding to approved therapies.
References
Ref 1 AMT-151 in Patients With Selected Advanced Solid Tumours
Ref 2 First-in-Human, Phase 1 Study of AMT-151, an Anti-Folate Receptor Alpha Antibody-Drug Conjugate, in Patients With Selected Advanced Solid Tumours, NCT05498597
Ref 3 Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene
Ref 4 A Study of A166 in Patients With Advanced Solid Malignant Tumors
Ref 5 HER2-positive Breast Cancer Project Initiated by Investigators
Ref 6 A first in-human study of A166 in patients with locally advanced/metastatic solid tumors which are HER2-positive or HER2-amplified who did not respond or stopped responding to approved therapies. Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 1049-1049.
Ref 7 Phase I study of A166, an antibodydrug conjugate in advanced HER2-expressing solid tumours. NPJ Breast Cancer. 2023 Apr 18;9(1):28. doi: 10.1038/s41523-023-00522-5.
Ref 8 An Open-clinical Trial Phase , Injection of A166 for HER2-positive Patients With Refractory Unresectable Locally Advanced or Metastatic Breast CancerKL166-IIS-001, NCT05346328
Ref 9 A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies, NCT03602079