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

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

REJOICE-Ovarian01 Phase 2/3 Trial of Raludotatug Deruxtecan Initiated in Patients with Platinum-Resistant Ovarian Cancer (Businesswire) - "Daiichi Sankyo...and Merck...announced today that the first patient has been dosed in the REJOICE-Ovarian01 phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan (R-DXd) in patients with platinum-resistant ovarian cancer. The phase 2 portion of the trial will be conducted to identify the dose of raludotatug deruxtecan to be used in the phase 3 part of the trial, which will evaluate raludotatug deruxtecan versus investigator’s choice of chemotherapy."

Trial status • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

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 | Recruiting | Sponsor: Daiichi Sankyo | Not yet recruiting ➔ Recruiting

Enrollment open • Fallopian Tube Cancer • Oncology • Solid Tumor

Raludotatug deruxtecan monotherapy among patients with previously treated ovarian cancer: Subgroup analysis of a first-in-human phase I study (SGO 2024) - P1, P2/3 | "Across the three dose groups, 40 patients (88.9%) had platinum-resistant disease, 29 (64.4%) had received prior bevacizumab, and 29 (64.4%) had received a prior PARP inhibitor. In unselected, heavily pretreated OVC patients, R-DXd demonstrated a manageable safety profile and encouraging preliminary efficacy, which supports further clinical development in OVC in the ongoing phase 2/3 trial (NCT06161025 [REJOICE-Ovarian01])."

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

Raludotatug Deruxtecan Shows Efficacy in Previously Treated Ovarian Cancer (Cancer Therapy Advisor) - P1 | N=140 | NCT04707248 | Sponsor: Daiichi Sankyo, Inc | "Dr Moore presented results with raludotatug deruxtecan at the SGO 2024 Annual Meeting on Women’s Cancer....The patients received raludotatug deruxtecan at doses of 4.8 mg/kg (n=13), 5.6 mg/kg (n=8), or 6.4 mg/kg (n=24). The median treatment duration was 17.9 weeks, and 66.7% of patients were still on study treatment at last follow-up. The confirmed overall response rate was 48.6%, and the disease control rate was 97.4%. One patient had a complete response, 17 had partial responses, and 18 had stable disease. The median duration of response was 11.2 months, and the median progression-free survival was 8.1 months."

P1 data • Ovarian Cancer

RALUDOTATATATUG DERUXTECAN (R-DXD; DS-6000) in Japan Patients with Ovarian Cancer: Subgroup Analysis of a Phase 1 Study (JSMO 2024) - No abstract available

Clinical • P1 data • Oncology • Ovarian Cancer • Solid Tumor

Raludotatug Deruxtecan, a CDH6-Targeting Antibody-Drug Conjugate with a DNA Topoisomerase I Inhibitor DXd, is Efficacious in Human Ovarian and Kidney Cancer Models. (PubMed, Mol Cancer Ther) - "R-DXd demonstrated potent antitumor activity against CDH6-expressing tumors in mice and an acceptable safety profile in monkeys. These findings indicate the potential of R-DXd as a new treatment option for patients with CDH6-expressing serous-type ovarian cancer and renal cell carcinoma in a clinical setting."

Journal • Preclinical • Genito-urinary Cancer • Kidney Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • CASP3 • CDH6 • CHEK1

For ovarian cancer and more! Daiichi Sankyo/Merck (MRK.US) CDH6-targeted ADC approved for clinical trials [Google translation] (Investing.com) - "Zhitong Finance APP has learned that on January 3, the official website of the Center for Drug Evaluation (CDE) of the State Food and Drug Administration of China recently announced that DS-6000a, a Class 1 new drug submitted by Daiichi Sankyo, has been approved for clinical use and is planned to be developed to treat past medical conditions. Patients with platinum-resistant high-grade ovarian, primary peritoneal, or fallopian tube cancer who have received at least first-line systemic anticancer therapy."

New trial • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

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 | Not yet recruiting | Sponsor: Daiichi Sankyo, Inc.

New P2/3 trial • Fallopian Tube Cancer • Oncology • Solid Tumor

Targeting cadherin-6 in epithelial ovarian cancer: Clinical significance of its expression and efficacy of raludotatug deruxtecan (R-DXd) in patient-derived cell models (ESMO 2023) - "DXd demonstrated cytotoxicity in all PDC models, regardless of CDH6 expression, whereas control ADC and anti-CDH6 naked antibody showed no growth inhibitory effects. Conclusions CDH6 is an attractive target for EOC and R-DXd is a promising agent for the treatment of CDH6-expressing EOC."

Clinical • Oncology • Ovarian Cancer • Solid Tumor • CDH6

Raludotatug deruxtecan (R-DXd; DS-6000) monotherapy in patients with previously treated ovarian cancer (OVC): Subgroup analysis of a first-in-human phase I study (ESMO 2023) - P1 | "Results As of 03 March 2023, 42 patients with OVC had received R-DXd at 4.8 (n = 7), 6.4 (n = 20), and 8.0 (n = 15) mg/kg: 40 (95%) had platinum-resistant disease, 29 (69%) had received prior bevacizumab, and 26 (62%) had received prior PARP inhibitors. Eleven of 21 GCIG-evaluable patients (52%) had a CA-125 response. Conclusions In heavily pretreated OVC patients without CDH6 preselection, R-DXd demonstrated acceptable safety and encouraging preliminary efficacy, which supports further clinical development in OVC."

Clinical • Monotherapy • P1 data • Oncology • Ovarian Cancer • Solid Tumor • CDH6 • MUC16

Raludotatug Deruxtecan Continues to Demonstrate Promising Clinical Activity in Patients with Advanced Ovarian Cancer in Early Trial (Yahoo Finance) - "'Following treatment with the current standard of care of platinum-based chemotherapy, disease progression in patients with advanced ovarian cancer is inevitable and underscores the need for new treatment options,' said Erika Hamilton, MD...'The response rate seen in these heavily pretreated patients is promising and further study of raludotatug deruxtecan in ovarian cancer is warranted.'"

Media quote

Raludotatug Deruxtecan Continues to Demonstrate Promising Clinical Activity in Patients with Advanced Ovarian Cancer in Early Trial (Daiichi Sankyo Press Release) - P1 | N=140 | NCT04707248 | Sponsor: Daiichi Sankyo, Inc | "Updated results from a subgroup analysis of a first-in-human phase 1 trial showed that raludotatug deruxtecan (R-DXd) continues to demonstrate promising clinical activity in patients with heavily pretreated platinum-resistant advanced ovarian cancer...A confirmed objective response rate (ORR) of 46% (95% CI: 32–61) by investigator assessment was observed in the subgroup of 50 patients with measurable ovarian cancer receiving raludotatug deruxtecan (4.8 to 8.0 mg/kg) in the phase 1 trial. One complete response (CR), 22 partial responses (PRs) and four unconfirmed responses were seen. A disease control rate (DCR) of 98% was observed. Median duration of response (DOR) was 11.2 months (95% CI: 3.0-NE) and median progression-free survival (PFS) was 7.9 months (95% CI: 4.4-12.4) as of the data cutoff of July 14, 2023....Patient enrollment in the dose expansion part of the trial remains underway in Asia and North America."

P1 data • Trial status • Ovarian Cancer

Daiichi Sankyo and Merck Announce Global Development and Commercialization Collaboration for Three Daiichi Sankyo DXd ADCs (Merck (MSD) Press Release) - "Daiichi Sankyo...and Merck...have entered into a global development and commercialization agreement for three of Daiichi Sankyo’s DXd antibody-drug conjugate (ADC) candidates: patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd). The companies will jointly develop and potentially commercialize these ADC candidates worldwide, except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply...The submission of a biologics license application (BLA) in the U.S. is planned by the end of March 2024 for patritumab deruxtecan, which is based on data from the HERTHENA-Lung01 Phase 2 trial...In conjunction with this transaction, Merck will record an aggregate pretax charge of $5.5 billion, or approximately $1.70 per share, reflecting the $4 billion upfront payment and the $1.5 billion in continuation payments."

BLA • Commercial • Licensing / partnership • Non Small Cell Lung Cancer • Ovarian Cancer • Small Cell Lung Cancer

Daiichi Sankyo Showcases Progress in Developing New Standards of Care for Patients with Industry-Leading DXd ADC Portfolio Across Multiple Cancers at ESMO (Businesswire) - "Daiichi Sankyo...will present new clinical research across its DXd antibody drug conjugate (ADC) portfolio in multiple types of cancer at the 2023 European Society for Medical Oncology (#ESMO23) Congress to be held October 20 - 24, 2023....Updates from other trials across Daiichi Sankyo’s DXd ADC portfolio include mini-oral sessions presenting an exploratory analysis of the intracranial efficacy of patritumab deruxtecan (HER3-DXd) in patients with EGFR-mutated metastatic NSCLC from the HERTHENA-Lung01 phase 2 trial, and updated data from an ongoing first-in-human phase 1 trial of raludotatug deruxtecan (R-DXd) in patients with previously treated ovarian cancer. A poster presentation also will feature updated clinical and biomarker results of ifinatamab deruxtecan (I-DXd) in patients with advanced solid tumors from an ongoing phase 1/2 trial."

P1 data • P1/2 data • P2 data • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor