SB38 (trastuzumab deruxtecan biosimilar) / Samsung - LARVOL DELTA

Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract or pancreatic tumors: a subgroup analysis of DESTINY-PanTumor02. (PubMed, ESMO Open) - P2 | "These data further support T-DXd as a recommended treatment in pretreated HER2 IHC 3+ tumors. Interpretation of PC cohort findings was limited by sample size and potentially confounded by the low number of patients with IHC 3+ PC. Safety was consistent with the known profile."

Journal • Pan tumor • Biliary Cancer • Biliary Tract Cancer • Interstitial Lung Disease • Oncology • Pancreatic Cancer • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

DESTINY-Gastric05 phase III trial of first-line trastuzumab deruxtecan, chemotherapy, and pembrolizumab in HER2-positive gastric or gastroesophageal junction cancer. (PubMed, ESMO Gastrointest Oncol) - P2, P3 | "Gastric or gastroesophageal junction (GEJ) cancers are usually diagnosed at advanced stages with poor prognoses and 5-year survival rates. DESTINY-Gastric05 (NCT06731478) is a global, multicenter, open-label, randomized, phase III trial to evaluate the efficacy and safety of first-line T-DXd 5.4 mg/kg plus 5-fluorouracil or capecitabine and pembrolizumab versus platinum-based chemotherapy with trastuzumab and pembrolizumab in patients with unresectable, locally advanced or metastatic, centrally confirmed HER2-positive (immunohistochemistry 3+ or immunohistochemistry 2+/in situ hybridization positive) gastric or GEJ cancer with a PD-L1 CPS ≥1. An exploratory cohort is to evaluate T-DXd plus 5-fluorouracil or capecitabine in patients with PD-L1 CPS <1."

Journal • P3 data • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1

First-line (1L) trastuzumab deruxtecan (T-DXd) + rilvegostomig (rilve) + fluoropyrimidine (FP) in HER2-positive (HER2+) gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJA), or esophageal adenocarcinoma (EA): DESTINY-Gastric03 (DG-03) Part 4 arm A results (AACR 2026) - P2 | "Pts received T-DXd + rilve + FP (5-fluorouracil or capecitabine). Early results showed promising antitumor activity with 1L T-DXd + rilve + FP in HER2+ GCs; safety findings were generally consistent with the known profiles of each agent as monotherapy, with no new safety signals observed. Data support further study of this 1L triplet regimen in HER2+ GCs."

Clinical • Late-breaking abstract • Esophageal Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1 • TIGIT

Human Epidermal Growth Factor Receptor 2 Quantification Using Computational Pathology to Identify Novel Biomarkers for Trastuzumab Deruxtecan-Treated Human Epidermal Growth Factor Receptor 2-Positive Gastric Cancer. (PubMed, JCO Precis Oncol) - "Our findings indicate that cSPS and DPC are predictive of T-DXd clinical outcomes, supporting the potential future use of QCS as a quantitative approach to identify patients with GC who might benefit most from T-DXd therapy."

Biomarker • Journal • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

First-line (1L) trastuzumab deruxtecan (T-DXd) regimens in advanced HER2-positive (HER2+) gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJA), or esophageal adenocarcinoma (EA): Exploratory analysis of baseline HER2-related biomarkers in DESTINY-Gastric03 (DG-03) Part 2 (AACR 2026) - P2 | "In Part 2, patients (pts) with previously untreated advanced HER2+ (IHC 3+ or IHC 2+/ISH+; local test) GC/GEJA/EA were enrolled across six arms and received either trastuzumab + chemotherapy (CT; fluoropyrimidine [FP; 5-fluorouracil or capecitabine] + cisplatin/oxaliplatin), T-DXd 6.4 mg/kg, T-DXd 6.4 mg/kg + FP, T-DXd 6.4 mg/kg + FP + pembrolizumab (pembro), T-DXd 6.4 mg/kg + pembro, or T-DXd 5.4 mg/kg + FP + pembro. Concordance results were broadly consistent with prior studies in GC. Elevated baseline HER2 IHC expression and HER2 amp were generally associated with higher ORRs for pts with HER2+ GCs treated with 1L T-DXd regimens, versus those with lower HER2 expression and/or without amplified HER2. Data provide further evidence of antitumor activity for 1L T-DXd combinations in HER2+ GCs."

Biomarker • Clinical • Late-breaking abstract • Metastases • Esophageal Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

Mechanistic and early clinical characterization of VRN101099, a selective HER2 inhibitor with receptor degradation activity (AACR 2026) - "Beyond catalytic activity, HER2 signaling is regulated by receptor dimerization, trafficking, and degradation, indicating that therapeutic strategies combining kinase inhibition with receptor downregulation may achieve more complete pathway suppression.Several HER2-directed tyrosine kinase inhibitors (TKIs), including tucatinib, zongertinib, and sevabertinib, have demonstrated clinical activity in HER2-driven cancers. Consistently, flow cytometry demonstrated reduced cell-surface HER2 following VRN101099 treatment, whereas tucatinib and zongertinib increased surface HER2 levels.Given that HER2-directed antibody-drug conjugates (ADCs), including trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1), require receptor internalization and lysosomal processing for activity, VRN101099 showed synergistic antitumor activity with these ADCs in HER2-driven xenograft models.A first-in-human, phase 1 dose-escalation study of VRN101099 monotherapy is ongoing. As of January..."

Clinical • First-in-human • Late-breaking abstract • Oncology • Solid Tumor • EGFR

…Samsung Launches Development of $10 Billion-Per-Year ADC Cancer Drug… Unprecedented Even in US and Europe (The Asia Business Daily) - "According to the bio industry on November 21, Samsung Bioepis's Enhertu biosimilar project has entered the early development stage ahead of preclinical trials....The company's announced plan to submit an ADC IND (investigational new drug application) in 2025 and enter Phase 1 clinical trials in 2026 pertains to its new drug development schedule, while the biosimilar business-its cash cow-is simultaneously advancing the Enhertu project."

New P1 trial • Oncology