Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0LNVKG
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| ADC Name |
Anvatabart opadotin
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| Synonyms |
anvatabart opadotin; ARX788; NCB001; JNJ-0683
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| Organization |
Ambrx (Top20 MNC) (Originator);NovoCodex Biopharmaceuticals
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| Drug Status |
Phase 2/3
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| Drug-to-Antibody Ratio |
1.9
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| Structure |
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| Antibody Name |
Anvatabart
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Antibody Info | ||||
| Antigen Name |
Receptor tyrosine-protein kinase erbB-2 (HER2 ECD2); Receptor tyrosine-protein kinase erbB-2 (HER2 ECD4)
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Antigen Info | ||||
| Payload Name |
Amberstatin 269 (AS269)
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Hydroxylamine-PEG4
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Linker Info | ||||
| Conjugate Type |
Non-natural Amino Acids
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| Combination Type |
opadotin
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| Special Approval(s) |
Fast track (FDA); Orphan drug (FDA)
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The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
| Indication | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | New Drug Application | Approved | |||||||||||||||||
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| Biliary tract cancer |
1 Trials
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| Breast cancer |
3 Trials
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1 Trials
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8 Trials
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1 Trials
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| Colorectal cancer |
1 Trials
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| Endometrial cancer |
1 Trials
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| Gastric cancer |
3 Trials
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1 Trials
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| Gastroesophageal junction adenocarcinoma |
1 Trials
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| Lung cancer |
1 Trials
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| Oral cavity cancer |
1 Trials
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| Unspecific solid tumor |
1 Trials
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1 Trials
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1 Trials
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| Urothelial cancer |
1 Trials
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General Information of The ADMET Data Related to This ADC(2027 Update)
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Elimination Half-Life (t1/2) | 100 | h |
Mean halflife for ARX788 and total antibody had approximately 100 hours at the dose of 1.5 mg/kg.
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[1], [2], [3] |
| Elimination Half-Life (t1/2) | 12.5 | day |
ARX788 exhibits high serum stability in mice and a relatively long ADC half-life of 12.5 days.
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[4] |
| Elimination Half-Life (t1/2) | 100 | h |
Mean T1/2 for ARX788 and total antibody had approximately 100 hours at the dose of 1.5 mg/kg.
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[5] |
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
57.10%
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| Patients Enrolled |
Patients with HER2+ mBC whose disease has progressed following T-DM1, T-DXd, and/or tucatinib-containing regimens.
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| Administration Dosage |
Administered with an initial dose of 1.50 mg/kg Q4W and subsequent doses of 1.30 mg/kg Q4W.
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| Related Clinical Trial | |||||
| NCT Number | NCT04829604 | Clinical Status | Phase 2 | ||
| Clinical Description | A global, phase 2 study of ARX788 in HER2-positive metastatic breast cancer patients who were previously treated with T-DXd. | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [7] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
33.30
46.20 28.60 % |
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| Patients Enrolled |
Twenty-two (73.30%) had gastric adenocarcinoma, and the rest (26.70%) had GEJ adenocarcinoma.
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| Administration Dosage |
At least one dose of ARX788, of whom 9 patients received 1.30 mg/kg, 14 received 1.50 mg/kg, and 7 received 1.70 mg/kg ARX788. The median treatment duration was 3.5 (range: 1-29) cycles.
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| Related Clinical Trial | |||||
| NCT Number | CTR20171162 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1 study of ACE-Breast-01 [ZMC-ARX788111 (CTR20171162)] to test the safety, PK, and antitumor activity of ARX788 in patients in China with HER2-positive metastatic breast cancer (MBC) whose disease had progressed on prior anti-HER2 treatments. The study includes dose escalation(N=69) to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) in patients with HER2-positive MBC. | ||||
| Primary Endpoint |
The MTD of ARX788 was not reached at doses of up to 1.50 mg/kg every 3 weeks. the RP2D in breast cancer studies was determined to be 1.50 mg/kg every 3 weeks. 33 of the 69 (47.83%) patients had an objective partial tumor response. For ARX788 1.50 mg/kg every 3 weeks, the objective response rate was 65.52% [19/29, 95% confidence interval (CI), 45.70-82.10], the disease control rate was 100.00% (95% CI, 81.20-100.00), and the median progression-free survival was 17.02 months (95% CI, 10.09-not reached).
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| Experiment 3 Reporting the Activity Date of This ADC | [7] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
37.90%
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| Patients Enrolled |
HER2-positive advanced gastric/gastroesophageal junction adenocarcinoma failing to respond to prior trastuzumab-based standard treatment, at least one dose.
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| Administration Dosage |
9 patients received 1.30 mg/kg, 14 received 1.50 mg/kg, and 7 received 1.70 mg/kg ARX788.
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| Related Clinical Trial | |||||
| NCT Number | CTR20171162 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1 study in HER2-positive advanced ug/GEJ adenocarcinoma was initiated to evaluate the safety and efficacy of ARX788. There were 22 males (73.3%) and 8 females (26.7%). Twenty-two (73.3%) had gastric adenocarcinoma,and the rest (26.7%) had GEJ adenocarcinoma. Twenty-seven patients (90%) underwent prior trastuzumab-containing therapy,eight of whom progressed within 6 months in the adjuvant or neoadjuvant phase. Twelve (40%) were treated with 2 or more lines of therapy (26) and eight of whom had 3 or more lines. All patients were treated with platinum-based and fluorouracil regimens,and eight with taxanes and three with irinotecan. Most participants (73.3%) had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1. All of them had at least one dose of ARX788,of whom 9 patients received 1.3 mg/kg,14 received 1.5 mg/kg,and 7 received 1.7 mg/kg ARX788. | ||||
| Primary Endpoint |
For ARX788 1.70 mg/kg, a median follow up of 10 (95% CI: 6.50-15.90) months,the median PFS was 4.10 (95% CI,1.40-6.40) months,and the median OS was 10.70 (95% CI,4.80-not reached) months.
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| Experiment 4 Reporting the Activity Date of This ADC | [8] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
65.52%
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| Patients Enrolled |
Incurable, locally advanced, or metastatic HER2-positive (immunohistochemistry [IHC] 3+ and/or fluorescence in situ 1 hybridization [FISH]-positive) breast cancer that progressed on greater and or 2 equal to two prior anti-HER2 treatment(s) in the advanced disease setting and 3 who provided written informed consent, patients had an Eastern 4 Cooperative Oncology Group (ECOG) performance status of 0-1.
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| Administration Dosage |
0.33 mg/kg Q3W, 0.66 mg/kg Q3W, 0.88 mg/kg Q4W, 0.88 mg/kg Q3W, 1.10 mg/kg Q4W, 1.10 mg/kg Q3W, 1.30 mg/kg Q4W, 1.30 mg/kg Q3W, and 1.50 mg/kg Q3W, intravenous infusion.
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| Related Clinical Trial | |||||
| NCT Number | CTR20171162 | Clinical Status | Phase 1 | ||
| Clinical Description | Patients with HER2-positive MBC received ARX788 at doses of 0.33, 0.66, 0.88, 1.10, 1.30, or 1.50 mg/kg every 3 weeks, or 0.88, 1.10, or 1.30 mg/kg every 4 weeks. The dose-limiting toxicity (DLT) was assessed for 84 days for pulmonary toxicity and at a duration of one cycle (21 or 28 days) for other toxicities. In total, 69 patients were enrolled. No DLT or drug-related deaths occurred. | ||||
| Primary Endpoint |
At 1.50 mg/kg every 3 weeks, the recommended phase II dose, the objective response rate was 65.52% [19/29, 95% confidence interval (CI), 45.70-82.10].
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| Other Endpoint |
The disease control rate was 100.00% (95% CI, 81.20-100.00), and the median progression-free survival was 17.02 months (95% CI, 10.09-not reached).
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| Experiment 5 Reporting the Activity Date of This ADC | [9] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
74.00
67.00 % |
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| Patients Enrolled |
ACE-Breast-01 (median 6 prior lines of therapy) and ACE-Pan tumor-01 trial (including breast, gastric/GEJ, NSCLC, ovarian, urothelial, biliary track, endometrial, and salivary gland cancer).
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| Administration Dosage |
0.33 - 1.5 mg/kg; Q3W or Q4W.
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| Related Clinical Trial | |||||
| NCT Number | NCT03255070 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1, multicenter, open-label, multiple dose-escalation and expansion study of ARX788, as monotherapy in advanced solid tumors with HER2 expression. | ||||
| Experiment 6 Reporting the Activity Date of This ADC | [10] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT05426486 | Clinical Status | Phase 2/3 | ||
| Clinical Description | A randomized, open label, multi-center phase 2-2i neoadjuvant study comparing the efficacy and safety of ARX788 combined with pyrotinib maleate versus TCBHP (trastuzumab plus pertuzumab with docetaxel and carboplatin) in patients with HER2-positive breast cancer. | ||||
| Experiment 7 Reporting the Activity Date of This ADC | [11] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT01042379 | Clinical Status | Phase 2 | ||
| Clinical Description | I-SPY trial (investigation of serial studies to predict your therapeutic response with imaging and molecular analysis 2). | ||||
| Experiment 8 Reporting the Activity Date of This ADC | [12] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT04983121 | Clinical Status | Phase 2 | ||
| Clinical Description | Efficacy and safety of pyrotinib maleate combined with ARX788 neoadjuvant treatment in stage 2-2I HER2-positive breast cancer patients who have poor outcomes after treatment with trastuzumab and pertuzumab. | ||||
| Experiment 9 Reporting the Activity Date of This ADC | [13] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT05018702 | Clinical Status | Phase 2 | ||
| Clinical Description | A prospective, single-arm, single-center phase 2 clinical study of recombinant humanized anti-HER2 monoclonal antibody-AS269 conjugate (ARX788) in the treatment of HER2-positive breast cancer patients with brain metastases. | ||||
| Experiment 10 Reporting the Activity Date of This ADC | [14] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT05018676 | Clinical Status | Phase 2 | ||
| Clinical Description | A single-arm, single-center phase 2 clinical study of recombinant humanized anti-HER2 monoclonal antibody-AS269 conjugate (ARX788) in the treatment of unresectable and/or metastatic breast cancer with low expression of HER2. | ||||
| Experiment 11 Reporting the Activity Date of This ADC | [15] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT05041972 | Clinical Status | Phase 2 | ||
| Clinical Description | A global phase 2 study to evaluate the efficacy and safety of ARX788 for selected HER2-mutated or HER2-amplified/overexpressed solid tumors. | ||||
| Experiment 12 Reporting the Activity Date of This ADC | [16] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT02512237 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1, multicenter, open-label, multiple dose-escalation study of ARX788, intravenously administered as a single agent in subjects with advanced cancers with HER2 expression. | ||||
| Experiment 13 Reporting the Activity Date of This ADC | [17] | ||||
| Efficacy Data | Progression Free Survival |
11.3 months
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| Patients Enrolled |
Eligibility requires HER2-positive (IHC 3+ or 2+/FISH+) stage II-III breast cancer patients (females, 18-75 years, ECOG 0-1) with adequate organ function. Key exclusions: prior antitumor therapy, metastatic/active malignancies (last 5 years), untreated infections, severe cardiac/pulmonary diseases, pregnancy, or uncontrolled comorbidities like hypertension/diabetes.
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| Administration Dosage |
Eligible patients were randomized (1:1) to receive ARX788 (1.5 mg/kg, IV, Q3W) or lapatinib plus capecitabine (LC: lapatinib 1250 mg QD; capecitabine 1000 mg/m2 BID, days 1-14, Q3W) and stratified by prior chemotherapy lines (0-1 versus >1) and visceral metastasis (yes versus no).
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| Related Clinical Trial | |||||
| NCT Number | NCT05426486 | Clinical Status | PHASE2|||PHASE3 | ||
| Clinical Description | A Randomized, Open Label, Multi-center Phase II-III Neoadjuvant Study Comparing the Efficacy and Safety of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) in Patients With HER2-positive Breast Cancer | ||||
| Primary Endpoint |
The primary endpoint is total pathological complete response (tpCR) rate over 3 years, defined as no residual invasive cancer in breast and axillary lymph nodes, allowing only intraductal carcinoma.
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| Other Endpoint |
Secondary endpoints include breast pCR (bpCR) rate, residual cancer burden (RCB) classification (0-III), best overall response rate (BORR), 5-year overall survival (OS), event-free survival (EFS), and adverse events (AEs) assessed per NCI-CTCAE v5.0, all measured within 3-5 years of follow-up.
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| Experiment 14 Reporting the Activity Date of This ADC | [18] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
54.5
23.3 % |
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| Patients Enrolled |
Eligible subjects ≥18 years with HER2+ metastatic breast cancer (≤5 prior therapies including T-DXd), measurable disease per RECIST 1.1, and stable brain metastases. Key exclusions: ILD/pneumonitis history, significant cardiac/ocular conditions, uncontrolled systemic diseases, recent radiotherapy (<7 days), active COVID-19, or investigational drug use within 14 days prior. Adequate organ function and stable prior toxicity (Grade ≤1) required.
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| Administration Dosage |
Between August 2020 and June 2023, 42 pts with HER2-pos and HER2-low BC with a median of 6 prior lines of therapy received intravenous ARX788 at either 1.5, 1.6, or 1.7 mg/kg every 21 days (Q3W) or every 28 days (Q4W).
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| Related Clinical Trial | |||||
| NCT Number | NCT04829604 | Clinical Status | PHASE2 | ||
| Clinical Description | A Global, Phase 2 Study of ARX788 in HER2-positive Metastatic Breast Cancer Patients Who Were Previously Treated With T-DXd | ||||
| Primary Endpoint |
Primary efficacy outcome measures Objective Response Rate (ORR) assessed per RECIST 1.1 criteria following ARX788 treatment, calculated as proportion of subjects achieving complete or partial responses within a 2-year timeframe.
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| Other Endpoint |
Secondary endpoints include Duration of Response (DOR), Best Overall Response (BOR), Disease Control Rate (DCR), Overall Survival (OS up to 2.5 years), Progression-Free Survival (PFS), safety assessments via CTCAE v5.0, and comprehensive pharmacokinetic profiling (Cmax, Ctrough, AUC) across multiple cycles evaluating ARX788 and its components.
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| Experiment 15 Reporting the Activity Date of This ADC | [17] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
63.80%
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| Patients Enrolled |
Eligibility requires HER2-positive (IHC 3+ or 2+/FISH+) stage II-III breast cancer patients (females, 18-75 years, ECOG 0-1) with adequate organ function. Key exclusions: prior antitumor therapy, metastatic/active malignancies (last 5 years), untreated infections, severe cardiac/pulmonary diseases, pregnancy, or uncontrolled comorbidities like hypertension/diabetes.
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| Administration Dosage |
Eligible patients were randomized (1:1) to receive ARX788 (1.5 mg/kg, IV, Q3W) or lapatinib plus capecitabine (LC: lapatinib 1250 mg QD; capecitabine 1000 mg/m2 BID, days 1-14, Q3W) and stratified by prior chemotherapy lines (0-1 versus >1) and visceral metastasis (yes versus no).
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| Related Clinical Trial | |||||
| NCT Number | NCT05426486 | Clinical Status | PHASE2|||PHASE3 | ||
| Clinical Description | A Randomized, Open Label, Multi-center Phase II-III Neoadjuvant Study Comparing the Efficacy and Safety of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) in Patients With HER2-positive Breast Cancer | ||||
| Primary Endpoint |
The primary endpoint is total pathological complete response (tpCR) rate over 3 years, defined as no residual invasive cancer in breast and axillary lymph nodes, allowing only intraductal carcinoma.
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| Other Endpoint |
Secondary endpoints include breast pCR (bpCR) rate, residual cancer burden (RCB) classification (0-III), best overall response rate (BORR), 5-year overall survival (OS), event-free survival (EFS), and adverse events (AEs) assessed per NCI-CTCAE v5.0, all measured within 3-5 years of follow-up.
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| Experiment 16 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
74
69 % |
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| Patients Enrolled |
Eligible subjects are adults (≥18 years) with HER2-positive advanced cancers (breast, gastric, or other solid tumors) refractory to prior HER2-targeted therapies. Phase 1b requires measurable disease (RECIST v1.1), ECOG 0-1, resolved prior toxicities (≤Grade 1), and adequate organ function. Exclusions include severe cardiac/neuropathy history, active infections (e.g., COVID-19/HIV/HBV/HCV), recent anticancer therapies (<14 days), or uncontrolled comorbidities. Contraception is mandated for participants.
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| Administration Dosage |
Experimental: ARX788 Phase 1a (Dose Escalation), ARX788 will be administered every 3 weeks (Q3W) or every 4 weeks (Q4W) via intravenous (IV) infusion. Patients will be enrolled into escalating dose levels during Dose Escalation period.Experimental: ARX788 Phase 1b (Dose Expansion), ARX788 will be administered every 3 weeks (Q3W) via intravenous (IV) infusion. Patients will receive the maximum tolerated dose during the Dose Expansion period of the study.
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| Related Clinical Trial | |||||
| NCT Number | NCT03255070 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1, Multicenter, Open-label, Multiple Dose-escalation and Expansion Study of ARX788, as Monotherapy in Advanced Solid Tumors With HER2 Expression | ||||
| Primary Endpoint |
This study evaluates ARX788's safety and immunogenicity through adverse event monitoring (Day 1 to 30 days post-treatment) and antitumor activity via RECIST v1.1-assessed objective response rates (ORR) in Phase 1b, with assessments every 6-8 weeks over 36 months.
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| Other Endpoint |
Key efficacy outcomes include ORR (CR+PR) per RECIST v1.1 over 18 months and pharmacokinetic profiling (AUC, half-life) of ARX788 and metabolites through 36 months. Immunogenicity is tracked via anti-drug antibody development during the study.
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| Experiment 17 Reporting the Activity Date of This ADC | [18] | ||||
| Efficacy Data | Disease control rate (DCR) |
81.8
76.7 % |
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| Patients Enrolled |
Eligible subjects ≥18 years with HER2+ metastatic breast cancer (≤5 prior therapies including T-DXd), measurable disease per RECIST 1.1, and stable brain metastases. Key exclusions: ILD/pneumonitis history, significant cardiac/ocular conditions, uncontrolled systemic diseases, recent radiotherapy (<7 days), active COVID-19, or investigational drug use within 14 days prior. Adequate organ function and stable prior toxicity (Grade ≤1) required.
Click to Show/Hide
|
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| Administration Dosage |
Between August 2020 and June 2023, 42 pts with HER2-pos and HER2-low BC with a median of 6 prior lines of therapy received intravenous ARX788 at either 1.5, 1.6, or 1.7 mg/kg every 21 days (Q3W) or every 28 days (Q4W).
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| Related Clinical Trial | |||||
| NCT Number | NCT04829604 | Clinical Status | PHASE2 | ||
| Clinical Description | A Global, Phase 2 Study of ARX788 in HER2-positive Metastatic Breast Cancer Patients Who Were Previously Treated With T-DXd | ||||
| Primary Endpoint |
Primary efficacy outcome measures Objective Response Rate (ORR) assessed per RECIST 1.1 criteria following ARX788 treatment, calculated as proportion of subjects achieving complete or partial responses within a 2-year timeframe.
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| Other Endpoint |
Secondary endpoints include Duration of Response (DOR), Best Overall Response (BOR), Disease Control Rate (DCR), Overall Survival (OS up to 2.5 years), Progression-Free Survival (PFS), safety assessments via CTCAE v5.0, and comprehensive pharmacokinetic profiling (Cmax, Ctrough, AUC) across multiple cycles evaluating ARX788 and its components.
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| Experiment 18 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Disease control rate (DCR) |
100%
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| Patients Enrolled |
Eligible subjects are adults (≥18 years) with HER2-positive advanced cancers (breast, gastric, or other solid tumors) refractory to prior HER2-targeted therapies. Phase 1b requires measurable disease (RECIST v1.1), ECOG 0-1, resolved prior toxicities (≤Grade 1), and adequate organ function. Exclusions include severe cardiac/neuropathy history, active infections (e.g., COVID-19/HIV/HBV/HCV), recent anticancer therapies (<14 days), or uncontrolled comorbidities. Contraception is mandated for participants.
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| Administration Dosage |
Experimental: ARX788 Phase 1a (Dose Escalation), ARX788 will be administered every 3 weeks (Q3W) or every 4 weeks (Q4W) via intravenous (IV) infusion. Patients will be enrolled into escalating dose levels during Dose Escalation period.Experimental: ARX788 Phase 1b (Dose Expansion), ARX788 will be administered every 3 weeks (Q3W) via intravenous (IV) infusion. Patients will receive the maximum tolerated dose during the Dose Expansion period of the study.
Click to Show/Hide
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| Related Clinical Trial | |||||
| NCT Number | NCT03255070 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1, Multicenter, Open-label, Multiple Dose-escalation and Expansion Study of ARX788, as Monotherapy in Advanced Solid Tumors With HER2 Expression | ||||
| Primary Endpoint |
This study evaluates ARX788's safety and immunogenicity through adverse event monitoring (Day 1 to 30 days post-treatment) and antitumor activity via RECIST v1.1-assessed objective response rates (ORR) in Phase 1b, with assessments every 6-8 weeks over 36 months.
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| Other Endpoint |
Key efficacy outcomes include ORR (CR+PR) per RECIST v1.1 over 18 months and pharmacokinetic profiling (AUC, half-life) of ARX788 and metabolites through 36 months. Immunogenicity is tracked via anti-drug antibody development during the study.
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| Experiment 19 Reporting the Activity Date of This ADC | [17] | ||||
| Efficacy Data | Complete response (CR) |
5.40%
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| Patients Enrolled |
Eligibility requires HER2-positive (IHC 3+ or 2+/FISH+) stage II-III breast cancer patients (females, 18-75 years, ECOG 0-1) with adequate organ function. Key exclusions: prior antitumor therapy, metastatic/active malignancies (last 5 years), untreated infections, severe cardiac/pulmonary diseases, pregnancy, or uncontrolled comorbidities like hypertension/diabetes.
Click to Show/Hide
|
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| Administration Dosage |
Eligible patients were randomized (1:1) to receive ARX788 (1.5 mg/kg, IV, Q3W) or lapatinib plus capecitabine (LC: lapatinib 1250 mg QD; capecitabine 1000 mg/m2 BID, days 1-14, Q3W) and stratified by prior chemotherapy lines (0-1 versus >1) and visceral metastasis (yes versus no).
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| Related Clinical Trial | |||||
| NCT Number | NCT05426486 | Clinical Status | PHASE2|||PHASE3 | ||
| Clinical Description | A Randomized, Open Label, Multi-center Phase II-III Neoadjuvant Study Comparing the Efficacy and Safety of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) in Patients With HER2-positive Breast Cancer | ||||
| Primary Endpoint |
The primary endpoint is total pathological complete response (tpCR) rate over 3 years, defined as no residual invasive cancer in breast and axillary lymph nodes, allowing only intraductal carcinoma.
|
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| Other Endpoint |
Secondary endpoints include breast pCR (bpCR) rate, residual cancer burden (RCB) classification (0-III), best overall response rate (BORR), 5-year overall survival (OS), event-free survival (EFS), and adverse events (AEs) assessed per NCI-CTCAE v5.0, all measured within 3-5 years of follow-up.
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| Experiment 20 Reporting the Activity Date of This ADC | [19] | ||||
| Patients Enrolled |
Eligible patients are adults (18-75 years) with HR±/HER2-low metastatic breast cancer (IHC 1+ or 2+/FISH-), prior systemic therapy exposure, measurable lesions, ECOG 0-1, and adequate organ function. Key exclusions include HER2-ADC pretreatment, active CNS metastases, uncontrolled comorbidities, interstitial lung disease, ocular disorders, recent anticancer therapies, pregnancy, or impaired trial compliance. Organ function thresholds and resolved prior toxicity (Grade ≤1) are required for enrollment.
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| Administration Dosage |
1.5 mgkg IV infusion on Day 1 of each 21-day treatment cycle.
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| Related Clinical Trial | |||||
| NCT Number | NCT05018676 | Clinical Status | PHASE2 | ||
| Clinical Description | A Single-arm, Single-center Phase II Clinical Study of Recombinant Humanized Anti-HER2 Monoclonal Antibody-AS269 Conjugate (ARX788) in the Treatment of Unresectable and/or Metastatic Breast Cancer With Low Expression of HER2 | ||||
| Primary Endpoint |
The primary efficacy endpoint is Objective Response Rate (ORR), defined as the proportion of subjects achieving complete or partial response per RECIST 1.1 criteria over a 2-year period.
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| Other Endpoint |
Secondary endpoints include Progression-Free Survival (PFS), Overall Survival (OS), Disease Control Rate (DCR), and Duration of Response (DOR), all evaluated within 2 years from treatment initiation. PFS measures time from first dose to progression/death; OS tracks survival from treatment start; DCR combines ORR with stable disease cases; DOR assesses sustained response in CR/PR patients.
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| Experiment 21 Reporting the Activity Date of This ADC | [20] | ||||
| Patients Enrolled |
Eligibility includes HR+/HER2+ metastatic breast cancer patients (18-75 years, ECOG 0-2) with untreated brain metastases, prior trastuzumab/taxane/EGFR-TKI exposure, and adequate organ function. Key exclusions: pneumomeningeal/cystic metastases, interstitial lung disease, recent antitumor therapies (within 1-2 weeks), active infections, severe allergies, pregnancy, or uncontrolled comorbidities.
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| Administration Dosage |
1.5 mg/kg IV infusion on Day 1 of each 21-day treatment cycle.
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| Related Clinical Trial | |||||
| NCT Number | NCT05018702 | Clinical Status | PHASE2 | ||
| Clinical Description | A Prospective, Single-arm, Single-center Phase II Clinical Study of Recombinant Humanized Anti-HER2 Monoclonal Antibody-AS269 Conjugate (ARX788) in the Treatment of HER2-positive Breast Cancer Patients With Brain Metastases | ||||
| Primary Endpoint |
The primary endpoint is CNS clinical benefit rate (CBR) assessed over 2 years using RANO-BM criteria, measuring the proportion of subjects achieving complete response, partial response, or stable disease.
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| Other Endpoint |
Secondary endpoints include progression-free survival (PFS), overall survival (OS), site of first progression, and adverse event (AE) monitoring over 2 years. PFS is defined as time from first dose to progression or death, while OS tracks time to death from any cause. AEs are evaluated per NCI CTCAE v5.0 to assess treatment safety.
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| Experiment 22 Reporting the Activity Date of This ADC | [21] | ||||
| Patients Enrolled |
Eligible participants include adults (≥18 years, ECOG 0-2) with HER2-low (IHC 1+/2+/FISH-) unresectable/metastatic breast cancer (HR+ or HR- cohorts), measurable lesions by RECIST 1.1, and controlled brain metastases if treated. Key exclusions: prior ARX-788/auristatin exposure, active ILD/pneumonitis, uncontrolled cardiac/pulmonary conditions, QTc prolongation (>450-470 ms), ocular diseases (keratitis), pregnancy, or malignancies requiring treatment within 3 years (exceptions: cured skin/thyroid cancers).
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| Administration Dosage |
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| Related Clinical Trial | |||||
| NCT Number | NCT06224673 | Clinical Status | PHASE2 | ||
| Clinical Description | Phase II Open-label Study of ARX788 (Anti-HER2 Antibody Drug Conjugate (ADC)) for Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer | ||||
| Primary Endpoint |
The primary endpoint is objective response rate (ORR) evaluated over 1 year using RECIST 1.1 criteria, reporting the proportion of participants achieving complete or partial response with 90% confidence intervals.
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| Other Endpoint |
Secondary objectives include duration of response (DOR), best overall response (BOR), disease control rate (DCR), median progression-free survival (PFS), median overall survival (OS), treatment-emergent AEs, ocular AE monitoring with visual/keratitis assessments, and adherence to preventive eye drop regimen - all analyzed within 1-2 years with 95% CIs where applicable.
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| Experiment 23 Reporting the Activity Date of This ADC | [22] | ||||
| Patients Enrolled |
Eligible patients are 18-75 years old with HER2+ unresectable BC, prior T-DXd treatment, and adequate organ function. Exclusions include CNS metastases, interstitial lung disease, active eye infections, cardiac insufficiency, or recent systemic therapy (except endocrine therapy within 28 days).
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| Administration Dosage |
ARX788,1.5 mg/kg IV infusion on Day 1 of each 21-day treatment cycle
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| Related Clinical Trial | |||||
| NCT Number | NCT06578286 | Clinical Status | PHASE2 | ||
| Clinical Description | Evaluate the Efficacy and Safety of ARX788 in Patients With HER2-positive Advanced Breast Cancer Whose Disease Has Progressed Following T-DXd Therapy | ||||
| Primary Endpoint |
The primary endpoint is objective remission rate (ORR), measured by CR or PR per RECIST 1.1, assessed up to 24 months.
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| Other Endpoint |
Secondary endpoints include disease control rate (DCR) (CR, PR, or SD), duration of relief (DOR), progression-free survival (PFS), overall survival (OS), and adverse events (TEAEs), monitored per RECIST 1.1 and CTCAE v5.0, assessed up to 50 months.
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| Experiment 24 Reporting the Activity Date of This ADC | [23] | ||||
| Patients Enrolled |
Exclusion criteria encompass known ARX788 hypersensitivity, active CNS metastases requiring treatment, symptomatic effusions requiring intervention, significant pulmonary/cardiac/ophthalmic comorbidities, uncontrolled hypertension, recent live vaccinations, pregnancy/breastfeeding, recent antitumor therapy (<28 days), cognitive impairments affecting consent comprehension, and any investigator-assessed conditions potentially compromising patient safety or protocol compliance.
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| Administration Dosage |
2.2 mg/kg IV infusion on Day 1 of each 42-day treatment cycle.
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| Related Clinical Trial | |||||
| NCT Number | NCT06663748 | Clinical Status | PHASE2 | ||
| Clinical Description | Evaluate the Efficacy and Safety of ARX788 Given Every 6 Weeks in Patients with HER2-positive Advanced Breast Cancer | ||||
| Primary Endpoint |
The study evaluates key efficacy parameters including objective response rate (ORR) based on RECIST 1.1, disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs) assessed by CTCAE v5.0. Pharmacokinetic parameters such as Cmax, tmax, t1/2, AUC (0-inf), AUC (0-last), λz, CL, Vz, Vss, and Ctrough are measured at specified cycle endpoints to characterize drug exposure and metabolism.
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| Other Endpoint |
Eligible participants aged 18-75 with HER2-positive (IHC3+ or FISH+) unresectable locally advanced, recurrent, or metastatic breast cancer who have received ≤2 prior chemotherapy lines (excluding hormonal therapy) and have ≥1 measurable lesion per RECIST1.1. Required criteria include recovery from prior treatment toxicities (≤Grade 1), adequate organ function, ECOG 0-1, and willingness to comply with study procedures and contraception requirements.
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| Experiment 25 Reporting the Activity Date of This ADC | [24] | ||||
| Patients Enrolled |
Eligible subjects must have life expectancy >12 weeks, BMI 18-32 kg/m2, HER2-positive advanced cancer with prior HER2-targeted therapy (where applicable), measurable disease per RECIST v1.1 (Phase 1b), and adequate organ function. Exclusions include severe allergies, uncontrolled CNS metastases, heart conditions, neuropathy, electrolyte imbalances, recent anticancer therapy/surgery/radiation, pregnancy, or inability to consent.
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| Administration Dosage |
Six cohorts with escalated dose levels of ARX788 at 0.33 mg/kg, 0.66 mg/kg, 1.3 mg/kg, 2.2 mg/kg, 2.9 mg/kg and 3.8 mg/kg will be administered every 3 weeks via intravenous infusion to determine the MTD.
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| Related Clinical Trial | |||||
| NCT Number | NCT02512237 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1, Multicenter, Open-label, Multiple Dose-escalation Study of ARX788, Intravenously Administered as a Single Agent in Subjects With Advanced Cancers With HER2 Expression | ||||
| Primary Endpoint |
The study aims to determine the maximum tolerated dose of ARX788 over 12 months, identifying the highest dose where fewer than 2 of 6 subjects experience dose-limiting toxicity.
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| Other Endpoint |
Safety and tolerability of ARX788 will be assessed over 30 months through adverse events, lab tests, and vital signs. Pharmacokinetic properties (AUC, half-life) will be measured after infusion cycles 1 and 3. Tumor response and immunogenicity (anti-ARX788 antibodies) will be evaluated over 18-30 months.
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| Experiment 26 Reporting the Activity Date of This ADC | [25] | ||||
| Patients Enrolled |
Eligible patients have untreated, measurable (≥2.5cm) stage II-III breast cancer with biomarker profiles matching study arms. Key requirements include adequate organ function, no distant metastases, and compatible MRI eligibility. Exclusions involve prior chemotherapy/radiation for current malignancy, uncontrolled comorbidities, or investigational drug use within 30 days.
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| Administration Dosage |
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| Related Clinical Trial | |||||
| NCT Number | NCT01042379 | Clinical Status | PHASE2 | ||
| Clinical Description | I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2) | ||||
| Primary Endpoint |
This study evaluates whether adding experimental agents to standard neoadjuvant therapy improves pathologic complete response (pCR) rates within biomarker-defined subgroups, assessed post-surgery after up to 36 weeks of treatment.
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| Other Endpoint |
The trial examines predictive biomarkers for pCR and residual cancer burden through serial blood/tissue collections. Secondary objectives include 3/5-year survival outcomes, safety profiling of investigational agents, and tumor volume changes via MRI at four timepoints during treatment and follow-up.
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| Experiment 27 Reporting the Activity Date of This ADC | [26] | ||||
| Patients Enrolled |
Exclusion criteria include prior interstitial lung disease or pneumonitis within 12 months, ongoing ocular conditions, recent anticancer therapy or radiotherapy, and significant surgeries within 21 days. Breast/gastric cancers are excluded from Cohort 4, and additional eligibility is determined by the study center.
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| Administration Dosage |
ARX788 will be administered by intravenous (IV) infusion every 3 weeks (Q3W).
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| Related Clinical Trial | |||||
| NCT Number | NCT05041972 | Clinical Status | PHASE2 | ||
| Clinical Description | A Global Phase 2 Study to Evaluate the Efficacy and Safety of ARX788 for Selected HER2-mutated or HER2-amplified/Overexpressed Solid Tumors | ||||
| Primary Endpoint |
The primary endpoint is Objective Response Rate (ORR) assessed by BICR per RECIST 1.1, defined as the proportion of subjects achieving CR or PR. Secondary endpoints include Duration of Response (DOR), Best Overall Response (BOR), Disease Control Rate (DCR), Progression-Free Survival (PFS), Overall Survival (OS), Time to Response (TTR), pharmacokinetic parameters (Cmax and Ctrough for ARX788, total antibody, and metabolites), and incidence of anti-drug antibodies (ADAs).
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| Other Endpoint |
Eligibility criteria include age ≥18, life expectancy >3 months, ECOG ≤1, and HER2 status confirmed via CLIA-certified lab. Cohorts 1, 2, and A require HER2 mutations in NSCLC, breast cancer, or other tumors without prior HER2 ADC treatment. Cohorts 3-5 include HER2-amplified BTC, CRC, ovarian, endometrial, NSCLC, and other tumors, with Cohort 5 allowing prior HER2 ADC. Subjects must have stable brain metastases and adequate organ function.
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References