trastuzumab envedotin (DP303c) / CSPC Pharma - LARVOL DELTA

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

A multicenter, open-label, dose escalation and expansion study of DP303c in patients with HER2-positive pre-treated advanced solid tumors (ESMO 2023) - P1 | "Pre-clinical study demonstrated similar to or better antitumor activity than T-DM1 in xenograft models. Conclusions DP303c demonstrated promising anti-tumor activity with acceptable safety in pts with pre-treated advanced solid tumors, especially BC. The pivotal phase II study in pts with BC is ongoing."

Clinical • Metastases • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Efficacy and safety of DP303c versus T-DM1 in HER2-positive advanced breast cancer: Interim analysis of a randomized, open-label, phase 3 trial (SABCS 2025) - "Pts were stratified by number of lines of previous systemic therapy (≤1 vs. >1), prior pertuzumab treatment (Yes vs. No), and visceral metastasis(Yes vs. No). DP303c demonstrated statistically significant and clinically meaningful improvement in PFS compared with T-DM1 in pts with HER2+ ABC who had been previously treated with trastuzumab and taxane. The safety profile of DP303c was manageable. These results support DP303c as a potential new treatment option for HER2+ ABC."

Clinical • Metastases • P3 data • P3 data: top line • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

First-in-human study of DP303c, a HER2-targeted antibody-drug conjugate in patients with HER2 positive solid tumors. (PubMed, NPJ Precis Oncol) - P1 | "Previous in vitro studies demonstrated that DP303c showed similar or better antitumor activity than T-DM1 in xenograft models. Based on safety and efficacy results, 3.0 mg/kg Q3W was determined as recommended phase 2 dose for DP303c. (Trial registration: ClinicalTrials.gov Identifier: NCT04146610)."

Journal • P1 data • Breast Cancer • Dry Eye Disease • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ophthalmology • Pain • Peripheral Neuropathic Pain • Solid Tumor • HER-2

CSPC Pharmaceutical Group has had its new drug application for Trastuzumab Envedotin Injection accepted by China’s National Medical Products Administration, marking a key milestone in its oncology pipeline. (TipRanks) - "The Class 1 therapeutic biological product is intended for adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received one or more anti-HER2 treatments."

China filing • HER2 Positive Breast Cancer

Case report: Spatiotemporal HER2 heterogeneity in AFP-producing gastric cancer: navigating long-term survival with molecularly-guided therapy in a refractory case. (PubMed, Front Immunol) - "Following progression on first-line FLOT chemotherapy, the 65-year-old male received second-line apatinib plus programmed death-1 (PD-1) inhibitor...Third-line anti-HER2 antibody-drug conjugate (ADC) DP303c rapidly achieved partial response with normalized AFP...Overall survival reached 79 months. This case highlights: 1) efficacy of anti-angiogenic and immunotherapy in AFPGC; 2) necessity of re-biopsy for detecting HER2 heterogeneity; and 3) potent activity of ADCs against HER2-converted metastases, enabling remarkable survival through sequential precision therapy."

Heterogeneity • Journal • Gastric Cancer • Oncology • Solid Tumor • AFP • HER-2

A Study of Sirolimus (Albumin-Bound) in Combination With Different ADCs Treatment of Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=444 | Recruiting | Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

New P1/2 trial • Solid Tumor

Antibody-drug conjugates in HER2-positive advanced or metastatic gastric cancer: a systematic review and meta-analysis. (PubMed, Front Oncol) - "Efficacy varied substantially among agents: trastuzumab deruxtecan (T-DXd) and DP303c demonstrated the highest ORRs (42.5% and 42.9%, respectively), whereas others, such as Trastuzumab emtansine (T-DM1), showed lower efficacy (20.6%). Managing toxicities such as anemia and neutropenia is essential for optimizing treatment. https://www.crd.york.ac.uk/PROSPERO/view/CRD420250653886, identifier PROSPERO CRD420250653886."

Journal • Retrospective data • Review • Gastric Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • HER-2

A PhaseⅠ/Ⅱ Study of Simmitinib or Irinotecan Liposomes Combined With DP303c in Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=252 | Not yet recruiting | Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd

New P1/2 trial • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

SinoVac: HER2 ADC (DP303c injection) has entered the key phase III clinical stage [Google translation] (Eastmoney.com) - "...On August 4, the company said on the interactive platform that the ADC series of products are currently progressing smoothly and are in the clinical development stage. The HER2 ADC (DP303c injection) is progressing rapidly and has entered the critical Phase III clinical stage."

Trial status • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Shanghai Runshi Pharmaceutical Technology Co., Ltd.'s application for implied license for clinical trials of drugs has been accepted [Google translation] (163.com) - "On May 27, according to the official website of CDE, Shanghai Runshi Pharmaceutical Technology Co., Ltd. and Shanghai Institute of Materia Medica, Chinese Academy of Sciences jointly applied for the drug 'Ximetinib Hydrochloride Tablets' and obtained implicit clinical trial approval, acceptance number CXHL2400288....Ximetinib Hydrochloride Tablets combined with DP303c Injection are used to treat patients with previously treated HER2-expressing locally advanced/metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma."

New trial • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

DP303c Versus Trastuzumab Emtansine in in Patients With HER2-positive Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=442 | Recruiting | Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

DP303c Versus Trastuzumab Emtansine in in Patients With HER2-positive Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=442 | Not yet recruiting | Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Metastases • New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

DP303c in Patients With HER2-positive Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=420 | Not yet recruiting | Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Metastases • New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A Study of DP303c in Patients With HER2-positive Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Metastases • New P1 trial • Oncology • Solid Tumor

An Innovative Site-Specific Anti-HER2 Antibody-Drug Conjugate with High Homogeneity and Improved Therapeutic Index. (PubMed, Onco Targets Ther) - "DP303c demonstrated remarkable anticancer efficacy against T-DM1 in xenograft models. DP303c was a strong candidate for the treatment of patients with HER2-positive cancer."

Journal • Oncology

DP303c in Patients With HER2-positive Unresectable Locally Advanced, Relapsed, or Metastaticbreast Cancer (clinicaltrials.gov) - P2 | N=191 | Not yet recruiting | Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

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