Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca - LARVOL DELTA

Trastuzumab deruxtecan in patients with metastatic non-small-cell lung cancer (DESTINY-Lung01): primary results of the HER2-overexpressing cohorts from a single-arm, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "Given the low antitumour activity of existing treatment options in this patient population, trastuzumab deruxtecan might have the potential to fill a large unmet need in HER2-overexpressing NSCLC. Our findings support further investigation of trastuzumab deruxtecan in patients with HER2-overexpressing NSCLC."

Journal • Metastases • P2 data • CNS Disorders • Fatigue • Hematological Disorders • Infectious Disease • Interstitial Lung Disease • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Septic Shock • Solid Tumor • Ventriculomegaly • HER-2

Prediction of survival after de-escalated neoadjuvant therapy in HER2+ early breast cancer: A pooled analysis of three WSG trials. (ASCO 2025) - P2, P2/3 | "WSG-ADAPT-HR-/HER2+ (NCT01817452) compared trastuzumab and pertuzumab (T + P, n=92) vs. T +P + pac (n=42); WSG-ADAPT-HR+/HER2+ (NCT01779206) compared trastuzumab emtansine (T-DM1, n=118) vs. T-DM1 + standard endocrine therapy (ET, n=125) vs. T + ET (n=129); WSG-TP-II (NCT03272477) compared neoadjuvant/adjuvant T + P + ET (n=100) vs. T + P + pac (n=107). This pooled analysis demonstrates that de-escalation trials in HER2+ eBC are feasible and safe for patients. 12× weekly paclitaxel + HER2 blockade is an effective and well-tolerated regimen with excellent 5-year survival. The favorable survival after pCR to sCTx-free NAT lays the groundwork for further de-escalation strategies, such as the currently ongoing WSG-ADAPT-HER2-IV evaluating T-DXd as NAT."

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

Trastuzumab deruxtecan (T-DXd) vs ramucirumab (RAM) + paclitaxel (PTX) in second-line treatment of patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) unresectable/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): Primary analysis of the randomized, phase 3 DESTINY-Gastric04 study. (ASCO 2025) - P3 | "T-DXd showed statistically significant and clinically meaningful improvement in OS over RAM + PTX in pts with HER2+ unresectable/metastatic GC/GEJA, reinforcing its use as a second-line standard of care. The safety profile of T-DXd 6.4 mg/kg was consistent with the known safety profile of T-DXd in GC/GEJA, with no new safety signals."

Clinical • Late-breaking abstract • Metastases • P3 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Inflammation • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09. (ASCO 2025) - P3 | "T-DXd + P demonstrated a statistically significant and clinically meaningful improvement in PFS vs THP that was consistently observed across all subgroups and may represent a new 1L standard of care in HER2+ a/mBC; no new safety signals were identified. NC, not calculable."

Clinical • Late-breaking abstract • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Inflammation • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2 • PIK3CA

Safety and efficacy of TQB2102, a novel bispecific anti-HER2 antibody–drug conjugate, in patients with advanced solid tumors: Preliminary data from the first-in-human phase 1 trial. (ASCO 2025) - P1, P3 | "The bispecific antibody component can target both extra-cellular domains II (pertuzumab binding site) and IV (trastuzumab binding site) of HER2...Most common tumor types included MBC (N = 80),Colorectal cancer(N = 37)and Gastric cancer (N = 23).Twenty-five (31%) MBC received prior anti-HER2 ADCs, including 21 pts received T-DM1, 8 pts received DS-8201.The median duration of follow-up was 8.15 months... TQB2102 is well tolerated with promising anti-tumor activity in pts with HER2-expressing cancer. These early signs of activity support a phase 3 trial in patients with HER2-low MBC that has been initiated (NCT06561607)."

Clinical • Metastases • P1 data • Anemia • Breast Cancer • Colorectal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer. (PubMed, N Engl J Med) - P3 | "Trastuzumab deruxtecan led to significantly longer overall survival than ramucirumab plus paclitaxel among patients with HER2-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Adverse events were common in both groups. Events of interstitial lung disease or pneumonitis with trastuzumab deruxtecan, a known risk, were mainly low-grade. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Gastric04 ClinicalTrials.gov number, NCT04704934.)."

Journal • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

DESTINY-Breast11: Neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC) (ESMO 2025) - P3 | "We report neoadjuvant T-DXd or T-DXd-THP vs dose-dense doxorubicin + cyclophosphamide (ddAC)-THP in a phase 3, multicenter, open-label, randomized study. Table: 291O T-DXd-THP ddAC-THP Full analysis set, n 321 320 pCR rate, %* 67.3 56.3 ΔpCR vs ddAC-THP, % (95% CI; P value) † 11.2 (4.0, 18.3; 0.003) − EFS hazard ratio (95% CI) ‡ 0.56 (0.26, 1.17) − Safety analysis set, n 320 312 Any SAE, n (%) 34 (10.6) 63 (20.2) Any AE leading to, n (%) Dose reduction 58 (18.1) 60 (19.2) Dose interruption 121 (37.8) 170 (54.5) Drug discontinuation 45 (14.1) 31 (9.9) Death 2 (0.6) 2 (0.6) Drug-related adjudicated ILD / pneumonitis, n (%) 14 (4.4) 16 (5.1) Grade ≥3 2 (0.6) 6 (1.9) 5 1 (0.3) 1 (0.3) Left ventricular dysfunction, n (%) 6 (1.9) 28 (9.0) Grade ≥3 1 (0.3) 7 (2.2) *By blinded central review † Stratified Miettinen & Nurminen method; P value crossed the 0.03 prespecified boundary ‡ 4.5% maturity Conclusions Neoadjuvant T-DXd-THP demonstrated a clinically meaningful and..."

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

Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): Interim analysis of DESTINY-Breast05 (ESMO 2025) - P3 | "Conclusions T-DXd showed a statistically significant and clinically meaningful IDFS and DFS benefit vs T-DM1, extending its superiority to post-neoadjuvant residual disease in pts with HER2+ early BC, and representing a potential new SOC. Safety of T-DXd was generally manageable with no new safety signals."

Clinical • Late-breaking abstract • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Phase I, dose-escalation study evaluating safety & efficacy of trastuzumab deruxtecan (T-DXd) in combination with ATR inhibitor (AZD6738, ceralasertib) in advanced solid tumors with HER2 expression (DASH) (ESMO 2025) - P1 | "Table: 939P Dose Level 1 (N = 6) 2 (N = 6) 3 (N = 6) 4 (N = 4) Total HER2 IHC 1/2+ (N = 15) 1/6 (17) 1/4 (25) 2/3 (67) 0/2 (0) 4/15 (27) 3+ (N = 7) - 1/2 (50) 2/3 (67) 1/2 (50) 4/7 (57) Total (N = 22) 1/6 (17) 2/6 (33) 4/6 (67) 1/4 (25) 8/22 (36) Table shows investigator-assessed objective response rate (%) per RECISTv1.1 Conclusions Preliminary evidence in this study showed that AZD6738 at 120 mg/d plus T-DXd at 5.4mg/kg was well-tolerated and yielded promising antitumor activity in heavily pretreated pts with high and low HER2-expressing advanced solid tumors. Expansion (colorectal and gastric-esophageal cancers) is ongoing and experience in other solid tumors is warranted."

Clinical • Combination therapy • Metastases • Esophageal Cancer • Gastric Cancer • Oncology • Solid Tumor • HER-2

A phase I/Ib study of IAM1363, a selective and brain penetrant HER2 inhibitor in participants (pts) with advanced cancers harboring HER2 alterations (ESMO 2025) - P1 | "Three of the 4 pts with PRs had received prior T-DXd. The pt with breast cancer had also received prior tucatinib...Most AEs were low grade and manageable in the outpatient setting. Antitumor activity was observed across disease types and HER2 alterations and was evident both systemically and intracranially in heavily pretreated pts."

Clinical • Metastases • P1 data • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • EGFR

Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer. (PubMed, N Engl J Med) - P3 | "Trastuzumab deruxtecan plus pertuzumab led to a significantly lower risk of progression or death than THP when used as first-line treatment for HER2-positive advanced or metastatic breast cancer, with no new safety signals. (Funded by AstraZeneca and Daiichi Sankyo; DESTINY-Breast09 ClinicalTrials.gov number, NCT04784715.)."

Journal • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Leukopenia • Neutropenia • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

DESTINY-Breast11 (DB-11) safety: neoadjuvant trastuzumab deruxtecan (T-DXd) alone or followed by paclitaxel + trastuzumab + pertuzumab (THP) vs dose-dense doxorubicin + cyclophosphamide followed by THP (ddAC-THP) in high-risk, HER2+ early-stage breast cancer (eBC) (SABCS 2025) - "Across arms, adjudicated drug-related ILD/pneumonitis rates were low, with fewer Grade ≥3 events with T-DXd and T-DXd-THP than ddAC-THP. LVD and neutropenia rates were highest with ddAC-THP. Although rates of N/V were higher with T-DXd and T-DXd-THP than ddAC-THP and peripheral neuropathy rates were higher with T-DXd-THP, events were generally low grade and nonserious, demonstrating a safety profile that is manageable with recommended treatment."

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

Pooled analysis by best confirmed response to trastuzumab deruxtecan and related biomarkers in patients with HER2-positive metastatic breast cancer from DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03. (PubMed, Ann Oncol) - "Patients with objective response to T-DXd, particularly those with CR, showed prolonged median PFS and OS. These results support T-DXd use across broad patient groups with HER2-positive mBC, including those with lower disease burden. Patients whose disease does not respond to T-DXd represent an unmet medical need, and research into more effective treatment approaches for these patients is warranted."

Biomarker • Journal • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ER • HER-2

Intracranial activity of datopotamab deruxtecan (Dato-DXd) for patients with HER2-negative breast cancer and leptomeningeal disease (LMD): Results from Cohort C of the DATO-BASE phase 2 trial (SABCS 2025) - P2 | "Patients had a median of 2.5 (range 0-6) prior lines of cytotoxic treatment, with 7 who had received prior ADCs (3 T-DXd, 2 SG, 2 both ADCs). In this exploratory cohort of DATO-BASE, Dato-DXd demonstrated promising intracranial activity in patients with HER2-negative MBC and LMD, including radiographic responses and improvement in neurological symptoms in most patients with baseline deficits. Outcomes appeared more favorable in ADC-naïve patients, although numbers were limited."

Clinical • P2 data • 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 • HER-2 • TACSTD2

Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of Asian patients (pts) with HER2+ advanced/metastatic breast cancer (a/mBC): A DESTINY-Breast09 analysis (ESMO Asia 2025) - P3 | "T-DXd + P demonstrated consistent efficacy as 1L treatment in Asian pts with HER2+ a/mBC, with no new safety signals. Table: 88MO Data in brackets are 95% CIs. *Estimate may change at updated analysis BICR, blinded independent central review; CI, confidence interval; DOR, duration of response; INV, investigator; mo, months; NC, not calculable; PFS, progression-free survival; ORR, objective response rate"

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Interim analysis results for the effectiveness and safety of trastuzumab deruxtecan in patients with HER2-low breast cancer and brain metastases: The HALLOW study (SABCS 2025) - P=N/A | "While longer follow-up and additional data are needed to confirm these findings, the current data provide tentative support for the effectiveness and safety of T-DXd in this BMs population including active BMs, which was not included in the DB-04 trial."

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

Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with HER2-positive (HER2+) advanced/metastatic breast cancer (a/mBC): patient-reported outcomes (PROs) from the DESTINY-Breast09 study (SABCS 2025) - P3 | "T-DXd + P was associated with more gastrointestinal symptoms but fewer skin/mucosal, nosebleed, and extremity swelling symptoms vs THP. Pain, fatigue, physical function, and overall patient-reported treatment impact were similar between regimens. Complementing the efficacy and safety results, PRO data support T-DXd + P as a new 1L treatment in HER2+ a/mBC providing durable pain control and maintenance of physical function, with distinct quality of life advantages compared with THP."

Clinical • Metastases • Patient reported outcomes • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Trojan horses at leptomeningeal cellular gates: Antibody-drug conjugates deliver cytotoxic payloads. (PubMed, Med) - "The DEBBRAH study showed promising results for patients with HER2-expressing (including HER2-low) metastatic breast cancer who received the antibody-drug conjugate (ADC) trastuzumab deruxtecan for leptomeningeal disease. ADCs represent a novel tool in the precision biomarker-based armamentarium, including in the tumor-agnostic setting, for targeting highly cytotoxic chemotherapy into cancer cells."

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

Enhertu: Data from P3 DESTINY-Ovarian01 trial (NCT06819007) for high-grade epithelial ovarian cancer post 2027 (AstraZeneca) - FY 2025 Results: Data from P1b DESTINY-LUNG03 trial (NCT04686305) for unresectable/metastatic NSCLC in 2027

P1 data • P3 data • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer

Enhertu: Data from P3 DESTINY-Lung06 trial (NCT06899126) for 1L HER2 overexpressing NSCLC post 2027 (AstraZeneca) - FY 2025 Results: Data from P3 DESTINY-Lung04 trial (NCT05048797) for HER2-mutated, unresectable, locally advanced/metastatic NSCLC in H1 2026

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Enhertu: Data from P1b/2 DESTINY-Gastric03 trial (NCT04379596) for gastric or gastroeosophogeal junction cancer in 2027 (AstraZeneca) - FY 2025 Results: Data from P3 DESTINY-BTC01 trial (NCT06467357) for treatment-naïve HER2- expressing biliary tract cancer post 2027

P1/2 data • P3 data • Biliary Tract Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology

Enhertu: Data from P3 DESTINY-Endometrial01 trial (NCT06989112) for HER2-expressing (IHC 3+/​2+), mismatch repair proficient (pMMR) endometrial cancer post 2027 (AstraZeneca) - FY 2025 Results: Data from P3 DESTINY-Endometrial02 trial (NCT07022483) for HER2-expressing endometrial cancer post 2027

P3 data • Endometrial Cancer • Gynecologic Cancers • Oncology

Enhertu: Data from monotherapy arm of P3 DESTINY-Breast09 trial (NCT04784715) for HER2-positive,1L advanced or metastatic breast cancer in H2 2026 (AstraZeneca) - FY 2025 Results: Data from P3 DESTINY-Gastric05 trial (NCT06731478) for HER2- positive gastric or gastroesophageal junction cancer post 2027

P3 data • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • HER2 Positive Breast Cancer • Oncology

Enhertu: Regulatory decision in EU/China/Japan for 1L HER2+ mBC (based on DESTINY-Breast09 trial) in H2 2026 (AstraZeneca) - FY 2025 Results: Regulatory decision in EU for HER2+ solid tumors (based on DESTINY-PanTumour02 trial) in H2 2026

China approval • EMA approval • Japan approval • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology

Electronic Patient-Reported Outcomes With Vital Sign Monitoring During Trastuzumab Deruxtecan Therapy: The PRO-DUCE Randomized Clinical Trial. (PubMed, JAMA Netw Open) - "While survival outcomes were unaffected, this monitoring strategy has potential to enhance patient-centered care. jRCT identifier: jRCTs031200387."

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