ifinatamab deruxtecan (DS-7300) / Daiichi Sankyo, Merck (MSD) - LARVOL DELTA

IDeate-Esophageal01: A phase III, randomized, open-label study of ifinatamab deruxtecan (I-DXd) in patients (pts) with pretreated advanced/metastatic esophageal squamous cell carcinoma (ESCC) (ESMO Asia 2025) - P1/2, P3 | "Pts (N≈510) are randomized 1:1 to receive I-DXd 12 mg/kg intravenously every 3 weeks or investigator's choice of chemotherapy (paclitaxel, docetaxel, or irinotecan) until disease progression, unacceptable toxicity, or other discontinuation criteria are met. Other secondary endpoints include duration of response and disease control rate by BICR, patient-reported outcomes, biomarker analysis, and safety. Enrollment is ongoing."

Clinical • IO biomarker • Metastases • P3 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • CD276

Ifinatamab deruxtecan (I-DXd) in extensive-stage (ES) small cell lung cancer (SCLC): Asian subgroup analysis from the phase II IDeate-Lung01 study (ESMO Asia 2025) - P2 | "I-DXd 12 mg/kg showed promising efficacy and a manageable safety profile in Asian pts with pretreated ES-SCLC; results were consistent with those in the overall 12-mg/kg population."

P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276

IDeate-Prostate02: A PHASE 1/2, OPEN-LABEL UMBRELLA SUBSTUDY OF IFINATAMAB DERUXTECAN-BASED TREATMENT COMBINATIONS OR AS MONOTHERAPY IN PARTICIPANTS WITH PREVIOUSLY TREATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (SUO 2025) - P1/2 | "Two monotherapy arms (Arm 1 [docetaxel] and Arm 2 [I-DXd]) will enroll participants into the Efficacy Phase, and 2 I-DXd combination arms (Arm 3: I-DXd+MK-5684; and Arm 4: I-DXd+ARPI [abiraterone acetate or enzalutamide; prior treatment dependent]) will enroll into the Safety Lead-in, followed by Efficacy Phase. Recruitment is ongoing. "

Clinical • Metastases • Monotherapy • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD276

IDeate-Prostate01: A PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF IFINATAMAB DERUXTECAN VERSUS DOCETAXEL IN PARTICIPANTS WITH PREVIOUSLY TREATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (SUO 2025) - P3 | "Recruitment is ongoing. "

Clinical • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD276

A Clinical Study of Gocatamig (MK-6070) and Infinatamab Deruxtecan (MK-2400) in People With Small Cell Lung Cancer (MK-6070-003) (clinicaltrials.gov) - P1/2 | N=170 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1/2 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Bispecific antibody-drug conjugates targeting DLL3×B7-H3 and DLL3×SEZ6 demonstrate potent anti-tumor activity in preclinical models of small-cell lung cancer (SITC 2025) - "Despite the approval of tarlatamab and ongoing development of DLL3- or B7-H3-targeted ADCs, tumor relapse and heterogeneity in target expression continue to pose challenges...We used in vitro internalization activity, in vivo anti-tumor efficacy in SCLC CDX or PDX models, and developability screening as primary selection criteria.Results The DLL3×B7-H3 bsAb showed stronger internalization in double positive cell lines than the parental monovalent arms and outperformed the naked antibodies of DS-7300 and rovalpituzumab (Rova)...The DLL3×SEZ6 bsADC demonstrated comparable efficacy to benchmark with same payload and showed more potent anti-tumor efficacy than parental monovalent ADCs in SCLC CDX models.DLL3×B7-H3 and DLL3×SEZ6 bsAbs exhibited excellent stability under stress conditions, suggesting them as promising candidates for CMC development.Conclusions DLL3×B7-H3 and DLL3×SEZ6 bsADCs represent two novel and complementary strategies for..."

Preclinical • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276 • DLL3 • SEZ6 • TOP1

KEYMAKER-U01 phase II substudies 01H/01I: Ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd), or docetaxel in stage IV non-small cell lung cancer (NSCLC) (ESMO 2025) - P2 | "Background The anti–PD-1 pembrolizumab plus chemotherapy (chemo) is a standard of care first-line therapy for metastatic NSCLC with no targetable genetic mutations. Legal entity responsible for the study Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Funding Daiichi Sankyo Company, Limited and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA."

IO biomarker • Metastases • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CDH6 • EGFR • ROS1

GenSci143, a Novel B7-H3 × PSMA Bispecific Antibody-Drug Conjugate (BsADC), Demonstrates Broad-Spectrum Preclinical Antitumor Efficacy with a Favorable Safety Profile (AACR-NCI-EORTC 2025) - "Clinical limitations of single-target agents include restricted efficacy in mCRPC monotherapy (e.g., DS-7300a [anti-B7-H3 ADC] and ARX517 [anti-PSMA ADC]), often attributed to tumor heterogeneity and variable target expression...Combination potential with enzalutamide (endocrine therapy) was evaluated in a PCa PDX model...The association with the SLFN11 biomarker may further optimize patient stratification. These results position GenSci143 as a promising therapeutic modality with enhanced efficacy and expanded patient coverage potential for mCRPC and beyond."

Preclinical • Castration-Resistant Prostate Cancer • Gastric Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • CD276 • FOLH1 • SLFN11 • TOP1

A phase Ib/II study of gocatamig (MK-6070; HPN328) and ifinatamab deruxtecan for relapsed/refractory extensive-stage small cell lung cancer (ES-SCLC) (ESMO 2025) - P1/2 | "Secondary objectives are to evaluate duration of response and progression-free survival by investigator assessment per RECIST v1.1 (part 1) and to characterize the pharmacokinetics and immunogenicity of gocatamig plus I-DXd combination therapy (part 1), I-DXd monotherapy (part 1), and gocatamig monotherapy (part 2). The 6070-002 study will enroll participants in Australia, Chile, China, Israel, Japan, South Korea, Spain, Türkiye, the United States of America, and other sites as the expansion gets underway."

P1/2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

IDeate-Lung02: A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=540 | Active, not recruiting | Sponsor: Daiichi Sankyo | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Intracranial activity of ifinatamab deruxtecan (I-DXd) in patients (pts) with extensive-stage (ES) small cell lung cancer (SCLC) and baseline (BL) brain metastases (BM): Primary analysis of IDeate-Lung01 (ESMO 2025) - P2 | "Table: 2760MO All pts with BL BM (N=65) No prior brain RT for BL BM (n=26) With prior brain RT for BL BM (n=39) BL brain TL (n=29) CNS ORR, n (%) 30 (46) 15 (58) 15 (38) 19 (66) 95% CI 34–59 37–77 23–55 46–82 CNS best overall response, n (%) Complete response 20 (31) 12 (46) 8 (21) 9 (31) Partial response 10 (15) 3 (12) 7 (18) 10 (34) Stable disease 29 (45) 9 (35) 20 (51) 9 (31) Progressive disease 1 (2) 0 1 (3) 0 Not evaluable 5 (8) 2 (8) 3 (8) 1 (3) CNS disease control rate, n (%) 59 (91) 24 (92) 35 (90) 28 (97) CNS duration of response, median (95% CI), months 6.2 (4.0–7.9) 6.7 (3.1–not estimable) 5.1 (3.0–7.9) 5.7 (3.1–7.1) CNS time to response, median (range), months 1.4 (0.9–8.5) 1.3 (1.1–2.8) 1.4 (0.9–8.5) 1.3 (0.9–3.0) Conclusions I-DXd demonstrated encouraging CNS activity in pts with ES-SCLC and BL BM regardless of prior RT for BL BM. The safety profile was manageable, similar between pts with and without BL BM, and consistent with the overall 12 mg/kg..."

Clinical • Brain Cancer • CNS Tumor • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276

Intracranial activity of ifinatamab deruxtecan (I DXd) in patients (pts) with extensive-stage (ES) small cell lung cancer (SCLC) and baseline (BL) brain metastases (BM): Primary analysis of IDeate-Lung01 (JADPRO 2025) - P2, P3 | "BACKGROUND • Approximately 10-20% of patients with SCLC have BM at diagnosis, increasing to 80% after 2 years** -For patients with BM at baseline, median OS from time of diagnosis is ~5 months, with a 3-year survival rate of 3.0% In the primary analysis of IDeate-Lung01 (Phase 2; NCT05280470), I-DXd 12 mg/kg Q3W demonstrated a systemic CORR of 48.2%, mDOR of 5.3 months, and mPFS of 4.9 months in 137 patients with previously treated ES-SCLC METHODS • We report a subgroup analysis of patients with asymptomatic (previously treated or untreated) BM identified by CNS BICR at study baseline delectable by CT/MRI brain scan at baseline (Figure 1) • Brain CT/MRI was performed at baseline for all patients, and for those with investigator-determined BM, Q6W for 36 weeks and Q12W thereafter Intracranial response was assessed by CNS BICR using a version of RECIST 1.1 modified for assessment of CNS tumors RESULTS • Baseline characteristics of patients with baseline BM: -..."

Clinical • Brain Cancer • CNS Tumor • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

IDeate-Lung01: Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (clinicaltrials.gov) - P2 | N=187 | Active, not recruiting | Sponsor: Daiichi Sankyo | Trial completion date: Nov 2025 ➔ Dec 2026

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Bridging Knowledge Gaps in Small Cell Lung Cancer: Data, Challenges and Priorities. (PubMed, Curr Oncol) - "Novel agents such as tarlatamab (DLL3-targeting) and ifinatamab deruxtecan (B7-H3-targeting) have shown encouraging efficacy in early-phase trials, though predictive markers remain elusive. A multi-dimensional approach combining tissue, blood, and immune profiling is essential to advance precision oncology in SCLC and improve patient selection for emerging therapies."

IO biomarker • Journal • Review • Tumor mutational burden • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • ASCL1 • DLL3 • NEUROD1 • PD-L1 • POU2F3 • YAP1

Trials-in-Progress Across Daiichi Sankyo’s Oncology Portfolio (Businesswire) - "A trial-in-progress poster will highlight the design of the DESTINY-Endometrial01 phase 3 trial...Three phase 2 trials-in-progress will include the HERTHENA-Breast03 trial (463eTiP)...the REJOICE-GI01 trial (1001TiP)...and, the KEYMAKER-U01 sub-studies 01H/01I (2081eTiP) evaluating ifinatamab deruxtecan, raludotatug deruxtecan or docetaxel in patients with stage IV NSCLC...The design of two additional early phase trials will be shared, including the phase 1/2 trial (2792TiP) evaluating ifinatamab deruxtecan and gocatamig in patients with relapsed/refractory ES-SCLC and a phase 1b trial (977P) of valemetostat..."

pMMR • Trial status • Biliary Tract Cancer • Endometrial Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Renal Cell Carcinoma • Triple Negative Breast Cancer • Urothelial Cancer

Ifinatamab deruxtecan: Primary completion of P2 KEYMAKERU01H trial (NCT06780085) for 2L non squamous NSCLC in Mar 2032 (Daiichi Sankyo) - WCLC 2025: Primary completion of P2 KEYMAKER-U01I trial (NCT06780098) for 2L non squamous NSCLC in Mar 2032

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology

IDeate-Lung02: a Phase 3 study of second-line ifinatamab deruxtecan in patients with relapsed small cell lung cancer. (PubMed, Future Oncol) - P3 | "Patients with small cell lung cancer (SCLC) have poor prognosis and limited treatment options beyond first-line therapy. Secondary endpoints include ORR by investigator; progression-free survival, duration of response, disease control rate, and time to response, all by BICR and investigator; patient-reported outcomes; and safety. IDeate-Lung02 will ascertain whether I-DXd treatment after only one prior line of systemic treatment improves outcomes for patients with relapsed SCLC compared with topotecan, amrubicin, or lurbinectedin.Clinical Trial Registration: NCT06203210."

Journal • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276

New data for investigational antibody-drug conjugates (ADCs) from Merck’s innovative pipeline will be presented at the Congress, including data for raludotatug deruxtecan (R-DXd), a CDH6 directed DXd ADC, and ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, both discovered by Daiichi Sankyo. (Merck (MSD) Press Release) - "Notably, research evaluating sacituzumab tirumotecan (sac-TMT), a TROP2-directed ADC being developed in collaboration with Kelun-Biotech will be shared in four presentations in certain patients with lung, breast, cervical and prostate cancer."

Clinical data • Platinum resistant • Castration-Resistant Prostate Cancer • Cervical Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Small Cell Lung Cancer

Ifinatamab Deruxtecan in Patients With Extensive-Stage Small-Cell Lung Cancer: Primary Analysis of the Phase 2 IDeate-Lung01 Trial. (PubMed, J Clin Oncol) - "I-DXd 12 mg/kg Q3W showed promising efficacy in patients with previously treated ES-SCLC. The observed safety profile was consistent with previous reports, with no new safety signals identified."

Journal • P2 data • Hematological Disorders • Interstitial Lung Disease • Lung Cancer • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • CD276

Ifinatamab deruxtecan: Primary completion of P2 IDeate-Prostate02 trial (NCT06863272) for mCRPC in Feb 2030 (Daiichi Sankyo) - WCLC 2025

Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer

Trials Supporting Three Recent Breakthrough Therapy Designations Showcased (Businesswire) - "Data from additional late-stage trials – DESTINY-Breast09, REJOICE-Ovarian01 and IDeate-Lung01....will be showcased at ESMO."

Clinical data • Late-breaking abstract • Platinum resistant • HER2 Positive Breast Cancer • Ovarian Cancer • Small Cell Lung Cancer

IDeate-Pantumor 01: Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Participants With Advanced Solid Malignant Tumors (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: Daiichi Sankyo | Trial completion date: Mar 2027 ➔ Oct 2029 | Trial primary completion date: Dec 2025 ➔ Apr 2027

First-in-human • Pan tumor • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Endometrial Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Prostate Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Ifinatamab deruxtecan: "I-DXd 12 mg/kg demonstrated remarkable efficacy in patients with previously treated ES-SCLC, particularly given the inclusion of populations often excluded from clinical trials"; Small cell lung cancer (Daiichi Sankyo) - WCLC 2025: "Confirmed ORR was 48.2%, median DOR was 5.3 months, median PFS was 4.9 months, and median OS was 10.3 months"

P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer

KEYMAKER-U06 Substudy 06E: Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06) (clinicaltrials.gov) - P1/2 | N=228 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting | Trial completion date: Feb 2031 ➔ Jan 2032 | Trial primary completion date: Feb 2031 ➔ Jan 2032

Enrollment open • Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Small cell lung cancer (SCLC): At the door of targeted therapies. (PubMed, Biomol Biomed) - "For decades, outcomes stagnated: most patients present with extensive-stage disease, screening rarely detects early tumors, surgery is seldom feasible, and platinum-etoposide remained the first-line standard with median overall survival (OS) 80% of SCLC, enables T-cell-redirecting therapy: the bispecific T-cell engager tarlatamab improved OS to 13.6 vs 8.3 months over standard second-line chemotherapy, with manageable cytokine release syndrome and occasional ICANS. B7 homolog 3 (B7-H3, CD276), uniformly expressed across SCLC subtypes and linked to poor prognosis, is another compelling target: the antibody-drug conjugate ifinatamab deruxtecan achieved a 54.8% response rate and meaningful survival in heavily pretreated patients, earning FDA Breakthrough designation. Together, DLL3- and B7-H3-directed therapies (with additional ADCs against Trop-2 and SEZ6 in development) are redefining second-line and later care. Key next steps include optimizing..."

IO biomarker • Journal • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276 • DLL3 • SEZ6