Aidixi (disitamab vedotin) / Rongchang Pharma, Pfizer - LARVOL DELTA

A Study of Disitamab Vedotin in Adults With HER2 Expressing Advanced Breast Cancer (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2029 ➔ Jan 2030 | Trial primary completion date: Apr 2027 ➔ Oct 2027

Enrollment open • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor

Intravesical Disitamab Vedotin (RC48) for HER2-Expressing High-Risk Non-Muscle-Invasive Bladder Cancer: A Single-Arm, Dose-Escalation Phase I Trial Study. (PubMed, MedComm (2020)) - P1, P1/2 | "Taken together, these findings indicate that intravesical RC48 was well tolerated and showed preliminary efficacy in HER2-expressing HR-NMIBC. The maximum tolerated dose was not reached, and further dose exploration is ongoing (NCT06378242)."

Journal • P1 data • Bladder Cancer • Genito-urinary Cancer • Infectious Disease • Nephrology • Oncology • Solid Tumor • HER-2

RC48 Plus Bevacizumab or Pyrotinib in HER2-Positive Metastatic Breast Cancer After T-DXd Failure: A Phase II Study (clinicaltrials.gov) - P2 | N=74 | Recruiting | Sponsor: The First Affiliated Hospital with Nanjing Medical University

New P2 trial • Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

DAB: RC48 in Combination With AK104 and Bevacizumab in OCCC (clinicaltrials.gov) - P2 | N=39 | Recruiting | Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Not yet recruiting ➔ Recruiting

Enrollment open • Platinum resistant • Platinum sensitive • Oncology • Ovarian Cancer • Ovarian Clear Cell Cancer • Solid Tumor

Efficacy and Safety of Tislelizumab in Combination With Disitamab-vedotin as Neoadjuvant Therapy for HER2-positive High-risk Upper Tract Urothelial Carcinoma (UTUC) (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: Tianjin Medical University Second Hospital | Trial primary completion date: Nov 2024 ➔ Dec 2026

Trial primary completion date • Oncology • Solid Tumor • Urothelial Cancer • HER-2 • PD-L1 • TMB

RC48-ADC Combined with Radiotherapy and Immunotherapy as Salvage Therapy for Advanced Solid Tumors with HER2 Expression: A Multicenter, Phase II Trial (ASTRO 2025) - No abstract available

Clinical • IO biomarker • Metastases • P2 data • Oncology • Solid Tumor • HER-2

HER2-Positive Urothelial Carcinoma: Current Evidence on Targeted Agents and Immunotherapy-Based Combinations. (PubMed, Target Oncol) - "On the other hand, HER2-targeted ADCs such as trastuzumab deruxtecan and disitamab vedotin have shown encouraging results. Moreover, this combination strategy may also offer some advantages in rewiring the tumour microenvironment, favouring an anti-cancer immune response. ADC and immune checkpoint inhibitor combinations are supported by solid preclinical evidence and are emerging as novel and promising tailored therapeutic approaches for advanced UC."

IO biomarker • Journal • Review • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • HER-2

Drug-tolerant persisting polyploid giant cancer cells mediate resistance to HER2-targeting antibody-drug conjugates. (PubMed, Cancer Lett) - "HER2-positive breast cancer (JIMT-1) and gastric cancer (MKN7, SNU-216) cells were treated with HER2-directed ADCs, trastuzumab emtansine, trastuzumab deruxtecan, XMT-1522, and disitamab vedotin (DV)...Drug-tolerant PGCCs upregulated nectin-4, and treatment with enfortumab vedotin, a nectin-4-targeted ADC, inhibited the regrowth of JIMT-1 xenografts. ADC treatment induces PGCCs that contribute to drug resistance. ADC-induced drug-tolerant PGCCs express nectin-4, which may serve as a potential therapeutic target."

Journal • Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • NECTIN4

KEYNOTE-D78: A Study of Disitamab Vedotin Alone or With Pembrolizumab in Urothelial Cancer That Expresses HER2 (clinicaltrials.gov) - P2 | N=372 | Recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Jun 2028 ➔ Apr 2029

Trial completion date • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • HER-2

UD-086 overcomes trastuzumab deruxtecan-resistance and has a best-in-class therapeutic index in MMAE-based antibody drug conjugates (EACR 2025) - "In NCI-N87 xenograft model, UD-086 showed three to10-fold potent efficacy than DS-8201a and 10-fold potent efficacy than disitamab vedotin, respectively. The therapeutic index of UD-086 is six. UD-086 shows strong efficacy in the DS-8201a resistance tumor models. Despite the conjugating AE with DAR of eight, UD-086 shows very high blood stability and has a significantly improved best in class therapeutic index compared to previous MMAE-based ADCs."

Oncology • CTSB • HER-2

Risk factors and therapeutic significance of HER2 overexpression in urothelial carcinoma. (PubMed, Pathol Res Pract) - "HER2 testing can be routinely done in patients with locally advanced or metastatic UC, multiple tumors and luminal. Neoadjuvant therapy (HER2-ADC) for locally advanced UC was found to significantly shrink tumors, providing a theoretical basis for organ preservation and functional protection in genitourinary tumor surgery. HER2-ADC may be effective and safe in the treatment of locally progressive or advanced UC."

Journal • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD44 • GATA3 • HER-2

Disitamab vedotin combined with fruquintinib in patients with HER2-expressing or HER2 mutation/amplified metastatic colorectal cancer refractory to at least two standard regimens: A prospective, exploratory, single-arm study. (ASCO 2025) - P4 | "The combination of RC48 and fruquintinib has demonstrated promising efficacy and a manageable safety in patients with HER2 -expressing or -amplified mCRC who have failed at least two lines of standard treatments.Patients with HER2 IHC 2+, 3+ and amplification appear to derive greater benefit from this therapeutic regimen."

Clinical • Metastases • Colorectal Cancer • Heart Failure • Leukopenia • Neutropenia • Oncology • Solid Tumor • HER-2

Multimodal cancer therapy consisting of antibody-drug conjugates and radiotherapy in cancer treatment (AACR 2025) - "Accordingly, combination of RT with ADCs targeting HER2: trastuzumab emtansine/deruxtecan/duocarmazine (T-DM1/T-DXd/T-Duo) and disitamab vedotin, TROP2: datopotamab deruxtecan and sacituzumab govitecan, EGFR: depatuxizumab MMAE, HER3: patritumab deruxtecan, Nectin4: enfortumab vedotin and CEACAM5: tusamitamab ravtansine were evaluated. Together, this study demonstrates that inherent sensitivity of tumor cells to different payload classes, DAR and TAA dynamic are of relevance for the efficacy of ADC. Informed selection of ADC exhibited synergistic effects with RT providing a novel multimodal and promising strategy for efficient cancer eradication."

Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • CEACAM5 • EGFR • ERBB3 • HER-2 • NECTIN4

An exploratory clinical study investigating the neoadjuvant treatment of HER2-low expressing, stage II-III breast cancer with disitamab vedotin combined with penpulimab (RCVDBCIIR005). (ASCO 2025) - P2 | "While the clinical benefit may be somewhat limited, the combination of Disitamab Vedotin and Penpulimab as neoadjuvant treatment for HER2-low early or locally advanced breast cancer demonstrates manageable safety and potential for furtheroptimization. This warrants additional investigation to refine and optimize treatment strategies."

Clinical • Breast Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • HER2 Breast Cancer • HER2 Positive Breast Cancer • Herpes Zoster • Oncology • Pruritus • Solid Tumor • Varicella Zoster • HER-2 • PD-L1

Efficacy and safety of distamab vedotin combined with carboplatin and bevacizumab for HER2-expressing platinum-sensitive ovarian cancer with prior PARPi treatment. (ASCO 2025) - P4 | "Funded by No funding sources reported Clinical Trial Registration Number: ChiCTR2400084761 Background: Disitamab Vedotin (DV) is a newly developed antibody-drug conjugate targeting human epidermal growth factor 2 (HER2) that is comprised of hertuzumab coupling monomethyl auristatin E(MMAE) via a cleavable linker. The preliminary data demonstrated notable efficacy in this pretreated PSOC population, including among those who may have PARPi resistance. DV combined with carboplatin and bevacizumab demonstrated manageable safety consistent with the known profile. The clinical trial is on-going."

Clinical • Platinum sensitive • Gastric Cancer • Leukopenia • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • HER-2

Updated results from a phase II study of perioperative disitamab vedotin (RC48-ADC) plus cadonilimab (AK104) for HER2-expressing muscle-invasive bladder cancer (MIBC). (ASCO 2025) - P2 | "Neoadjuvant and adjuvant RC48-ADC plus AK104 demonstrated favorable efficacy and a manageable safety profile, supporting its potential as a valuable treatment modality for HER2-expressing MIBC. Long-term benefits and further understanding the role of this combination therapy in the perioperative setting of MIBC will be critical to advance treatment strategies."

IO biomarker • P2 data • Bladder Cancer • Cardiovascular • Genito-urinary Cancer • Oncology • Pneumonia • Solid Tumor • CTLA4 • HER-2 • PD-1 • PD-L1

Safety and efficacy of neoadjuvant disitamab vedotin in combination with pertuzumab with or without toripalimab for HER2-positive breast cancer: An open-label phase II trial. (ASCO 2025) - P2 | "The combination of disitamab vedotin, pertuzumab and toripalimab showed promising antitumor activity and manageable safety profiles. This regimen may offer a potential chemotherapy-free treatment option for patients in this population. The synergistic effects between HER2-directed antibody-drug conjugates (ADCs), immune checkpoint inhibitors and HER2-directed monoclonal antibodies are worthy of further exploration."

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

Real-world use of antibody drug conjugates (ADCs) in metastatic bladder cancer: Analysis of 10,204 patients treated in clinical practice. (ASCO 2025) - "Enfortumab vedotin (EV) and Sacituzumab Govitecan (SG) are approved by regulatory agencies worldwide, and several other compounds are being investigated in clinical trials...Of all patients, only 922 (9%) were treated with any ADCs as a current or prior line of treatment, including EV, SG, Disitamab Vedotin, Tisotumab Vedotin, and Trastuzumab Deruxtecan... ADCs represent a new therapeutic option for the treatment of mBC, but our data suggest limited access worldwide despite regulatory approvals and clinical guideline recommendations. There is a geographic variation in the percentage of patients treated with ADCs, suggesting higher access in the US. Potential reasons include drug cost limiting access and approval delays in different regions."

Clinical • Metastases • Real-world • Real-world evidence • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • NECTIN4

Neoadjuvant treatment with disitamab vedotin monotherapy in patients with HER2-overexpressing muscle invasive bladder cancer (MIBC): An open-label, single-arm, phase II study. (ASCO 2025) - P=N/A | "Neoadjuvant RC48-ADC monotherapy treatment demonstrated promising antitumor activity with a manageable safety profile in pts with HER2-overexpressing MIBC. These results support the essential value of RC48-ADC for the neoadjuvant treatment of MIBC."

Clinical • IO biomarker • Monotherapy • P2 data • Alopecia • Bladder Cancer • Diabetes • Fatigue • Genito-urinary Cancer • Immunology • Oncology • Pain • Solid Tumor • Urothelial Cancer • HER-2

Disitamab vedotin (RC48), tislelizumab, and S-1 as first-line therapy for HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results from the RCTS trial. (ASCO 2025) - P2 | "Recent trials revealed that HER2-targeted antibody-drug conjugates, including RC48 and Trastuzumab Deruxtecan, combined with anti-PD1 antibody, have also shown promising efficacy in this population. The combination of RC48, tislelizumab and S-1 as a first-line therapy shows encouraging response rates and survival benefits in HER2-overexpressing GC/GEJC, especially in HER2-positive or CPS ≥1 patients, supporting further evaluation in randomized controlled trials. Clinical trial: NCT05586061."

Clinical • Metastases • Esophageal Cancer • Fatigue • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Solid Tumor • HER-2 • PD-L1

PUNCH03: A phase II study of disitamab vedotin combined with tislelizumab and bacillus Calmette-Guerin (BCG) in Her2-positive high-risk non-muscle-invasive bladder cancer (HR NMIBC). (ASCO 2025) - P1 | "Secondary end points were bladder-preservation rate, OS and safety. Our study estimated a RFS rate at 12 months was no less than 85% and the study would enroll 38 pts."

P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • HER-2

Prospective, single arm, phase II clinical study of disitamab vedotin combined with XELOX as first-line treatment for HER2 positive advanced gastric cancer or gastroesophageal junction adenocarcinoma (ChiCTR) - P2 | N=30 | Not yet recruiting | Sponsor: Gansu Cancer Hospital; Gansu Cancer Hospital

New P2 trial • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

Real-world effectiveness and safety of RC48-ADC combined with PD-1 inhibitors for patients with metastatic urothelial carcinoma: A retrospective multicenter study. (ASCO 2025) - "The use of 3-weekly cycles of RC48 in combination with PD-1 inhibitor as first-line therapy is both effective and safe for real-world patients with la/ mUC, regardless of disease status or impaired renal function. Patient demographics and clinical features in metastatic urothelial carcinoma treated."

Metastases • Real-world • Real-world effectiveness • Real-world evidence • Retrospective data • Anemia • Dermatology • Fatigue • Hematological Disorders • Oncology • Pain • Pruritus • Solid Tumor • Urothelial Cancer

The potential of disitamab vedotin in bladder preservation during neoadjuvant therapy for bladder cancer: A comparative analysis with the GC regimen. (ASCO 2025) - "The Disitamab Vedotin regimen demonstrated better efficacy and safety compared to the GC regimen in neoadjuvant therapy for bladder cancer. Its higher CR rate and potential for bladder preservation make it a promising option for organ-sparing treatment. However, given the small sample size and the retrospective nature of this study, further validation through large-scale, multicenter prospective studies is required."

Clinical • Bladder Cancer • Genito-urinary Cancer • Leukopenia • Neutropenia • Oncology • Pain • Solid Tumor • Urothelial Cancer

Efficacy and safety of RC48-ADC in triple-negative breast cancer subtypes: FUSCC-TNBC-umbrella trial results. (ASCO 2025) - P1/2 | "RC48-ADC showed promising antitumor activity with manageable safety in pretreated TNBC patients with low HER2 expression, particularly in LAR subtype. The 35.0% ORR in heavily pretreated TNBC warrants further investigation in biomarker-selected populations. Clinical trial information: NCT03805399."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Solid Tumor • Triple Negative Breast Cancer