anvatabart opadotin (JNJ-0683) / Zhejiang Medicine, J&J - LARVOL DELTA

ACE-Breast-03: A phase 2 study of ARX788, a novel next-generation anti-HER antibody-drug conjugate in HER2-positive metastatic breast cancer patients previously treated with trastuzumab deruxtecan (SABCS 2023) - P2 | "If recently progressed on T-DXd or trastuzumab emtansine (T-DM1), a new biopsy for HER2 status is required. Descriptive statistics will be used to evaluate anticancer activity, safety, and tolerability. The study is currently recruiting patients."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Safety, tolerability, pharmacokinetics, and antitumor activity of SHR-A1811 in HER2-expressing/mutated advanced solid tumors: A global phase 1, multi-center, first-in-human study (AACR 2023) - "Background: SHR-A1811 is an ADC comprised of a humanized anti-HER2 monoclonal antibody (trastuzumab), a cleavable linker, and a DNA topoisomerase I inhibitor payload. SHR-A1811 was well-tolerated and showed promising antitumor activity in heavily pretreated advanced solid tumors.Table 1. Subgroup analyses of ORRNo. of prior treatment lines in metastatic setting in all pts (N=250)HER2 positive BC (N=108)HER2-low BC (N=77)Other tumor types (N=65)≤381.8% (45/55)58.7% (27/46)36.7% (18/49)>381.1% (43/53)51.6% (16/31)31.3% (5/16)Prior anti-HER2 therapies in pts with BC (N=185)*HER2 positive BC (N=108)HER2-low BC (N=77)All BC (N=185)Any82.2% (88/107, 73.7-89.0)68.8% (11/16, 41.3-89.0)80.5% (99/123, 72.4-87.1)Trastuzumab81.9% (86/105, 73.2-88.7)75.0% (9/12, 42.8-94.5)81.2% (95/117, 72.9-87.8)Pertuzumab83.0% (39/47, 69.2-92.4)100% (5/5, 47.8-100)84.6% (44/52, 71.9-93.1)Pyrotinib86.9% (53/61, 75.8-94.1)71.4% (5/7, 29.0-96.3)85.3% (58/68, 74.6-92.7)Lapatinib80.0% (28/35,..."

Clinical • Metastases • P1 data • PK/PD data • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • HER-2

Neoadjuvant ARX788 plus pyrotinib versus trastuzumab, pertuzumab, docetaxel and carboplatin for HER2-positive breast cancer: a randomised phase 2b trial. (PubMed, Nat Commun) - P2/3 | "Interstitial lung disease (ILD)/pneumonitis and ocular events were observed with ARX788 plus pyrotinib, indicating a distinct safety profile. These findings offer clinical insights into the potential of dual HER2-targeted blockade with an ADC and TKI as an optional neoadjuvant strategy for patients with early or locally advanced HER2-positive breast cancer."

Clinical • Journal • P2b data • Anorexia • Breast Cancer • Fatigue • Hepatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Liver Failure • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

ACE-Breast-02: A pivotal phase II/III trial of ARX788, a novel anti-HER2 antibody-drug conjugate (ADC), versus lapatinib plus capecitabine for HER2+ advanced breast cancer (ABC). (ASCO 2024) - "Research Funding: No funding sources reported. ARX788 significantly prolonged PFS comparing to LC in patients with HER2+ ABC previously treated with trastuzumab and taxane. While ocular toxicity and interstitial lung disease were common and manageable, its hematological and GI toxicities under no prophylactic premedication compared favorably with already available ADCs."

Metastases • P2/3 data • Breast Cancer • Dermatology • Dry Eye Disease • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Ophthalmology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

ACE-Breast-02: a randomized phase III trial of ARX788 versus lapatinib plus capecitabine for HER2-positive advanced breast cancer. (PubMed, Signal Transduct Target Ther) - "This phase III trial aimed to compare ARX788, a site-specific, construct-homogeneous antibody-drug conjugate, with lapatinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) who had progressed on one line of trastuzumab based regimen. Six treatment-related deaths occurred, with three cases possibly related to ILD. ARX788 significantly improved PFS compared with LC in patients with HER2-positive ABC with a distinct toxicity profile, supporting it as a potential treatment option."

Clinical • Journal • P3 data • Breast Cancer • Dermatology • Dry Eye Disease • Gastrointestinal Disorder • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Ophthalmology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

ARX788 for Treating Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Laura Huppert, MD, BA | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

ARX788 for Treating Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Laura Huppert, MD, BA | Trial primary completion date: Dec 2028 ➔ Mar 2029 | Trial completion date: Dec 2028 ➔ Mar 2029

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Pathologic complete response rates (pCR) after the novel HER2 ADC ARX788: Results from the I-SPY2.2 trial (SABCS 2025) - P2 | "I-SPY2.2 validates the use of personalized neoadjuvant therapy guided by molecular diagnostics and response-adaptive strategies tailored to each individual patient. NCT01042379"

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • HER-2

Trial in Progress: 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 (SABCS 2025) - P1, P2 | "Exploratory endpoints include blood- and tumor-based biomarker analyses and patient-reported outcomes (PROs). Enrollment to all cohorts will begin in the third quarter of 2025."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Incidence and predictors of interstitial lung disease associated with antibody-drug conjugates in breast cancer: a systematic review and meta-analysis (SABCS 2025) - "ILD, including pneumonitis, is a clinically relevant toxicity of ADC therapy in BC. Incidence and severity vary across agents. Payload type emerged as the strongest predictor of ILD risk, underscoring its importance in ADC development and patient selection."

Retrospective data • Review • Breast Cancer • Oncology • Solid Tumor

Efficacy and safety of ARX788 for individuals with HER2-positive breast cancer and brain metastases (ACE-Breast-06): a single-arm, phase 2 trial in China. (PubMed, EClinicalMedicine) - P2 | "Eligible participants were patients (aged 18-75 years) with HER2-positive breast cancer who had received trastuzumab, taxane, and tyrosine kinase inhibitor (TKI) treatment, and also had at least one measurable active brain metastatic lesion (≥1 cm). Future prospective studies incorporating patient-reported outcomes are needed to better capture the clinical benefit of ARX788. National Natural Science Foundation of China; National Key Research and Development Program of China; Shanghai Science and Technology Innovation Action Plan; and Beijing Science and Technology Innovation Medical Development Foundation Key Project."

Journal • P2 data • Breast Cancer • Dry Eye Disease • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Ophthalmology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03) (clinicaltrials.gov) - P2 | N=71 | Active, not recruiting | Sponsor: Ambrx, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Phase I study of ARX788 plus toripalimab in advanced solid tumors with expansion in HER2-low advanced breast cancer (ESMO 2025) - P1 | "Background ARX788, a novel HER2-targeted ADC with site-specific conjugation of a tubulin inhibitor payload, demonstrated synergistic anti-tumor activity with pembrolizumab in preclinical studies. ILD onset was comparable to monotherapy. Further evaluation is warranted."

Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Bystander effect in antibody-drug conjugates: navigating the fine line in tumor heterogeneity. (PubMed, Crit Rev Oncol Hematol) - "Clinically, ADCs with bystander effects (e.g., trastuzumab deruxtecan), demonstrate superior efficacy compared to non-bystander ADCs (e.g., trastuzumab emtansine)...For instance, while the bystander effect allows payloads to penetrate BSB and increase the killing range, non-bystander ADCs like ARX788 may offer comparable efficacy with reduced toxicity in homogeneous settings...Future research should focus on three key areas: (1) quantifying bystander contributions in vivo; (2) clarifying spatiotemporal regulation of payload diffusion by TME factors such as hypoxia and binding-site barriers; and (3) validating combinatorial strategies, including Fc engineering, internalization induction, and TME remodeling, to maximize therapeutic indices. Bridging these gaps will refine ADC design paradigms, aligning with precision oncology's goal of optimizing efficacy while minimizing systemic toxicity."

Heterogeneity • Journal • Review • Oncology

HER2 alterations in non-small cell lung cancer (NSCLC): from biology and testing to advances in treatment modalities. (PubMed, Front Oncol) - "Furthermore, we present updated clinical trial data for published HER2-targeted agents and explore ongoing clinical trials examining combinatorial therapies and next-generation HER2-targeted agents such as zongertinib, A166, ARX788, SHRA1811, and others. Given the rapid evolution in this field, our review offers a timely and comprehensive synthesis of the current state and future directions for HER2-altered NSCLC."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • TYK2

Treatment-related toxicities of antibody-drug conjugates in breast cancer: A Bayesian network meta-analysis. (ASCO 2025) - " A total of 9307 patients in 17 RCTs of five different ADCs (ado-trastuzumab emtansine [T-DM1], sacituzumab govitecan [SG], trastuzumab deruxtecan [T-DXd], datopotamab deruxtecan [Dato-DXd], and ARX788) were included. This Bayesian network meta-analysis highlights significant variability in TRAEs among different ADCs in breast cancer therapy. T-DM1 was primarily associated with thrombocytopenia and hepatic toxicities, while SG and T-DXd were associated with neutropenia, anemia, GI disorders, and dermatological TRAEs. Our findings may help with selection of ADC therapies for patients with breast cancer, facilitating personalized approaches to minimize treatment-related toxicities."

Retrospective data • Alopecia • Anemia • Breast Cancer • CNS Disorders • Dermatology • Fatigue • Gastrointestinal Disorder • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Musculoskeletal Diseases • Neutropenia • Oncology • Pruritus • Solid Tumor • Thrombocytopenia

ARX788 for Treating Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Laura Huppert, MD, BA | Trial completion date: Jul 2028 ➔ Oct 2028 | Trial primary completion date: Jul 2028 ➔ Oct 2028

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Screening or Early Detection of Brain Metastases and the Treatment in the Era of New Agents (GBCC 2025) - "Advances in systemic therapy have been greatest in HER2-positive breast cancer, where the current NCCN guidelines include a growing list of CNS-active regimens, such as tucatinib-capecitabine-trastuzumab, T-DXd, T-DM1, high dose trastuzumab and pertuzumab, neratinib-capecitabine, and lapatinib-capecitabine...There are a number of novel blood-brain-barrier (BBB) penetrant HER2-targeted tyrosine kinase inhibitors (e.g. ZN1041, IAM1363) in early-phase clinical trials. For patients with HER2-negative tumors, the data are more sparse; however, activity of chemotherapy drugs such as capecitabine, anthracyclines, platinums, and eribulin has been reported...Ongoing clinical trials are testing a wide variety of ADCs, such as patritumab deruxtecan, datopotamab deruxtecan, ARX788, and others...For example, the ELECTRA trial is testing the combination of elacestrant and abemaciclib. Overall, the expanding array of systemic options with clinically meaningful intracranial activity, as..."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

Antibody-drug conjugates in elderly patients with breast cancer. (PubMed, Breast) - "This review explores the application of antibody-drug conjugates (ADCs), such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), in treating breast cancer among elderly populations. Emerging ADCs, including datopotamab deruxtecan and ARX-788, show promise but lack extensive geriatric-specific data. While the ADCs offer encouraging results in terms of efficacy and safety, with appropriate dose adjustments, further research is needed to optimize their use in elderly patients with breast cancer."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

ACE-BREAST-03: A phase 2 trial evaluating ARX788, an anti-HER2 antibody drug conjugate (ADC), for the treatment of HER2+ metastatic breast cancer (mBC) in patients who have been previously treated with trastuzumab deruxtecan (T-DXd) (SABCS 2024) - P2 | "The HER2-targeted ADC, T-DXd, improved PFS and OS vs T-DM1 as second- line treatment for HER2+ mBC and is now the preferred treatment option in this setting...A phase 2/3 study in China demonstrated that ARX788 had significantly improved PFS compared with the combination of lapatinib and capecitabine (HR 0.64 [0.49, 0.82], p = 0.0006) in patients treated with prior trastuzumab and taxane (ASCO 2024 Abstract 1020)...Tumor status is assessed every 9 weeks through 27 weeks and every 12 weeks thereafter. The study is currently enrolling in the US."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03) (clinicaltrials.gov) - P2 | N=71 | Recruiting | Sponsor: Ambrx, Inc. | Trial completion date: Dec 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Evaluate the efficacy and safety of ARX788 given every 6 weeks in patients with HER2-positive advanced breast cancer (ChiCTR) - P2 | N=44 | Sponsor: He'nan Cancer Hospital; He'nan Cancer Hospital

New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Another HER2 antibody-drug conjugate, the Phase III clinical study data of ARX788 is released! [Google translation] (new.qq.com) - P2/3 | N=441 | ACE-Breast-02 (CTR20201708) | Sponsor: Zhejiang Medicine Co., Ltd./Zhejiang Xinma Biopharmaceutical Co., Ltd. | "The latest report on ARX788 comes from the 47th San Antonio Breast Cancer Symposium in 2024....The results of the study showed that for HER2-positive breast cancer patients who had previously been treated with the HER2-targeted drug trastuzumab and paclitaxel, ARX788 significantly prolonged the patients' progression-free survival time compared with the treatment regimen of lapatinib combined with capecitabine. The median progression-free survival time of ARX788 was 11.33 months, while the median progression-free survival time of the control group was 8.25 months. The median duration of remission of ARX788 was 12.45 months, while the median progression-free survival time of the control group was 8.34 months."

P3 data • HER2 Positive Breast Cancer

ARX788 for the treatment of HER2+ advanced breast cancer: clear efficacy and manageable toxicity [Google translation] (163.com) - P1b/2 | N=138 | ACE-Breast-08 (CTR20213419) | Sponsor: Zhejiang Medicine Co., Ltd. | "This phase I study explored the prospect of ARX788 as a third-line treatment for HER2+ advanced breast cancer...The results showed that ARX788 showed encouraging efficacy in patients with HER2-positive advanced breast cancer who had previously received trastuzumab and anti-HER2-TKI treatment: In the intention-to-treat population, the IRC-assessed cORR was 44.9% (95%CI: 36.5%-53.6%), including 3 complete responses (CR) and 59 partial responses (PR); The cORR assessed by the investigator was 42.0% (95%CI: 33.7%-50.7%), including 3 CRs and 55 PRs. The median follow-up time was 14.78 months, the progression-free survival (PFS) assessed by IRC was 5.68 months (95%CI: 5.49 months-8.25 months), and the PFS assessed by the investigator was 6.90 months (95%CI: 5.45 months-7.89 months)....The median overall survival (OS) has not yet been reached, and the 1-year OS rate is 81.3%."

P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

ARX788 for patients with HER2-positive advanced breast cancer: characterization, time course, and monitoring and management of adverse event from the phase III ACE-Breast-02 study (SABCS 2024) - P2/3 | " 441 eligible patients were randomized 1:1 to receive ARX788 or lapatinib plus capecitabine. ARX788 demonstrated a unique safety profile with less hematological and GI toxicities. Liver enzyme elevations were commonest with predominantly low grades, while ocular toxicity and ILD were common and manageable. The low rate of dose discontinuation suggested that, when with proactive monitoring and appropriately adequate management, these AEs did not pose a challenge to its clinical benefit."

Adverse events • Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2