raludotatug deruxtecan (DS-6000) / Daiichi Sankyo, Merck (MSD) - LARVOL DELTA

REJOICE-Ovarian02: A phase Ib/II study of raludotatug deruxtecan (R-DXd) with other anticancer agents in participants (pts) with relapsed ovarian cancer (OC) after platinum-based chemotherapy (ESMO-GC 2025) - P1, P1/2 | "Herein, we describe the phase Ib portion of a phase Ib/2, open-label, dose-escalation study (REJOICE-Ovarian02; NCT06843447) to assess safety, tolerability, and preliminary antitumor activity of R-DXd combined with carboplatin or paclitaxel in pts with platinum-sensitive recurrent OC (PSOC) or with bevacizumab in pts with platinum-resistant recurrent OC (PROC). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Legal entity responsible for the study Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA."

Clinical • P1/2 data • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor • CDH6

Raludotatug deruxtecan (R-DXd) monotherapy in patients (pts) with heavily pretreated platinum-sensitive ovarian cancer (PSOC): Subgroup analysis of a phase I study (ESMO-GC 2025) - P1 | "Median number of prior lines of therapy was 4 (range, 2–6); 14 pts (77.8%) had received prior bevacizumab and 15 (83.3%) prior PARP inhibitor. Editorial acknowledgement Medical writing support was provided by Natalie Dennis of BOLDSCIENCE, Inc., and was funded by Daiichi Sankyo, Inc. Legal entity responsible for the study Daiichi Sankyo, Inc."

Clinical • Monotherapy • P1 data • Platinum sensitive • Oncology • Ovarian Cancer • Solid Tumor • CDH6

A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01) (clinicaltrials.gov) - P2 | N=96 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

REJOICE-GI01: A Study of Raludotatug Deruxtecan (R-DXd) in People With Gastrointestinal Cancers (MK-5909-005) (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: May 2029 ➔ Jan 2029

Trial completion date • Gastrointestinal Cancer • Oncology • Solid Tumor

REJOICE-PanTumor01: A phase 2 signal-seeking study of raludotatug deruxtecan (R-DXd) in patients with advanced or metastatic gynecologic or genitourinary tumors. (ASCO 2025) - P1, P2, P2/3 | "PFS and DOR will be analyzed using the Kaplan–Meier method (2-sided 95% CI). Study enrollment began in January 2025."

Clinical • Metastases • P2 data • Pan tumor • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Endometrial Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer • CDH6

Additional Data and Trials-in-Progress Across Daiichi Sankyo’s Oncology Portfolio at ASCO (Daiichi Sankyo Press Release) - "Oral presentations also will highlight initial results from the TUXEDO-3 phase 2 trial (#2005) evaluating patritumab deruxtecan in patients with metastatic breast cancer or advanced NSCLC and active brain metastases and in patients with leptomeningeal carcinomatosis/disease from advanced solid tumors, as well as results from a phase 1 trial (#10003) evaluating valemetostat, a dual EZH1 and EZH2 inhibitor, in pediatric patients with malignant solid tumors...Additional DXd ADC trials-in-progress poster presentations include the REJOICE-PanTumor01 phase 2 trial (TPS3158) evaluating raludotatug deruxtecan (R-DXd) in patients with locally advanced or metastatic gynecologic or genitourinary cancers, IDeate-PanTumor02 phase 1b/2 trial (TPS3157) evaluating ifinatamab deruxtecan in patients with recurrent or metastatic solid tumors and a substudy of KEYMAKER-U06, a phase 1/2 trial (TPS4209) evaluating ifinatamab deruxtecan in combination with pembrolizumab..."

Clinical data • Trial status • Acute Myelogenous Leukemia • Esophageal Squamous Cell Carcinoma • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Triple Negative Breast Cancer

QLS5133-a novel CDH6-targeting antibody-drug-conjugate for solid tumors (AACR 2025) - "Additionally, QLS5133 was able to achieve a durable response even after resistance to Mirvetuximab soravtansine (FRα ADC/ImmunoGen) in preclinical models. The promising efficacy, superior tolerability, and favorable PK profile support the potential of QLS5133 as a novel therapeutic agent to address the high unmet needs in patients with variable CDH6-expressing cancers. QLS5133 will enter clinical trials."

Endocrine Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Thyroid Gland Carcinoma • CDH6 • FOLR1

REJOICE-GI01: A Study of Raludotatug Deruxtecan (R-DXd) in People With Gastrointestinal Cancers (MK-5909-005) (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

A Clinical Study of Raludotatug Deruxtecan in People With Ovarian Cancer (MK-5909-003) (clinicaltrials.gov) - P1/2 | N=78 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Platinum resistant • Platinum sensitive • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor

A Study of Raludotatug Deruxtecan in Participants With Advanced/Metastatic Solid Tumors (REJOICE-PanTumor01) (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Daiichi Sankyo | Not yet recruiting ➔ Recruiting

Enrollment open • Pan tumor • Endometrial Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

A Clinical Study of Raludotatug Deruxtecan in People With Ovarian Cancer (MK-5909-003) (clinicaltrials.gov) - P1/2 | N=78 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1/2 trial • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor

REJOICE-GI01: A Study of Raludotatug Deruxtecan (R-DXd) in People With Gastrointestinal Cancers (MK-5909-005) (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2 trial • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01) (clinicaltrials.gov) - P2 | N=96 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC | Initiation date: Feb 2025 ➔ May 2025

Trial initiation date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

KEYMAKER-01I: Substudy 01I: A Study of Investigational Agents in Participants With Previously Treated Stage IV Squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01I/KEYMAKER-U01I) (clinicaltrials.gov) - P2 | N=144 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC | Initiation date: Feb 2025 ➔ May 2025 | Trial primary completion date: Sep 2030 ➔ Mar 2032

Trial initiation date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Consolidated Financial Results for the First Nine Months of the Year Ending March 31, 2025 (Fiscal 2024) (Daiichi Sankyo Press Release) - "Revenue in the first nine months of the year ending March 31, 2025 increased by JPY194.3 billion, or 16.6% year on year, to JPY1,367.6 billion; Revenue increased year on year due to the achieved growth with global mainstay products such as Enhertu (generic name: trastuzumab deruxtecan, T-DXd/DS-8201)....Research and development expenses increased by JPY43.8 billion, or 17.0% year on year, to JPY300.6 billion due to increased R&D investment in 5DXd ADCs (trastuzumab deruxtecan, datopotamab deruxtecan: Dato-DXd/DS-1062, patritumab deruxtecan: HER3-DXd/U3-1402, ifinatamab deruxtecan: I-DXd/DS-7300, DS-6000)."

Commercial • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer

Substudy 01I: A Study of Investigational Agents in Participants With Previously Treated Stage IV Squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01I/KEYMAKER-U01I) (clinicaltrials.gov) - P2 | N=144 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2 trial • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01) (clinicaltrials.gov) - P2 | N=96 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors (clinicaltrials.gov) - P1 | N=179 | Active, not recruiting | Sponsor: Daiichi Sankyo | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: Nov 2024 ➔ Apr 2025

Enrollment closed • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor

REJOICE-Ovarian01: A Study of Raludotatug Deruxtecan (R-DXd) in Subjects With Platinum-resistant, High-grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2/3 | N=650 | Active, not recruiting | Sponsor: Daiichi Sankyo | Recruiting ➔ Active, not recruiting

Enrollment closed • Fallopian Tube Cancer • Oncology • Solid Tumor

Safety and Efficacy Study of Investigational Agents as Monotherapy or in Combination With Pembrolizumab (MK-3475) for the Treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Need of Second-Line Therapy (MK-3475-B98/KEYNOTE-B98) (clinicaltrials.gov) - P1/2 | N=110 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Recruiting | N=80 ➔ 110 | Trial completion date: Nov 2026 ➔ Nov 2029 | Trial primary completion date: Nov 2026 ➔ May 2026

Combination therapy • Enrollment change • Enrollment open • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Study of Raludotatug Deruxtecan in Participants With Advanced/Metastatic Solid Tumors (REJOICE-PanTumor01) (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Daiichi Sankyo

New P2 trial • Endometrial Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

Novel antibody-drug conjugates based on DXd-ADC technology. (PubMed, Bioorg Chem) - "This review provides a comprehensive assessment of drugs developed with DXd-ADC technology, with a focus on mechanisms of action, pharmacokinetics studies, preclinical data, and clinical outcomes for DS-8201a, U3-1402, DS-1062a, DS-7300a, DS-6157a, and DS-6000a. By integrating existing data, we aim to provide valuable insights into the current therapeutic status and future prospects of these novel agents."

Journal • Review • Oncology

REJOICE-Ovarian01: A phase 2/3 study of raludotatug deruxtecan (R-DXd) in patients with platinum-resistant ovarian cancer (OVC). (ASCO 2024) - P1, P2/3 | "Eligible patients are adults with high-grade serous or endometrioid OVC, primary peritoneal cancer, or fallopian tube cancer with acquired platinum resistance and 1–3 prior systemic lines of therapy (LOT) including prior bevacizumab treatment (unless ineligible) and prior mirvetuximab soravtansine treatment for patients whose tumors are folate receptor alpha-positive (unless ineligible or not available)...In the Phase 3 part, approximately 450 patients will be randomized 1:1 to receive either R-DXd or treatment of physician's choice (TPC: paclitaxel, pegylated liposomal doxorubicin, gemcitabine, or topotecan)...OS and one QoL subscale will be tested hierarchically after PFS. Study enrollment is planned to start in February 2024."

Clinical • P2/3 data • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CDH6 • FOLR1

Daiichi Sankyo Highlights Progress in Creating New Standards of Care for Patients Across Multiple Cancers at ASCO (Businesswire) - "Trials-in-progress presentations include the IDeate-Lung02 phase 3 trial (TPS8126) evaluating ifinatamab deruxtecan (I-DXd) in patients with relapsed small cell lung cancer, the REJOICE-Ovarian01 phase 2/3 trial (TPS5625) evaluating raludotatug deruxtecan (R-DXd) in patients with platinum-resistant ovarian cancer, the HERTHENA-PanTumor01 phase 2 trial (TPS3164) evaluating patritumab deruxtecan (HER3-DXd) in patients with locally advanced or metastatic solid tumors, and the first-in-human phase 1/2 trial (TPS3165) of DS-3939 in patients with advanced solid tumors."

Trial status • Gynecologic Cancers • Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor

DS-6000: “DS-6000 demonstrated strong clinical activity and manageable safety profile in Ph1 study platinum resistant ovarian cancer cohort“; Ovarian cancer (Daiichi Sankyo) - FY2023 Results

P1 data • Gynecologic Cancers • Oncology • Ovarian Cancer