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

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

A Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Daiichi Sankyo, Inc. | Trial completion date: Jul 2023 ➔ Oct 2024 | Trial primary completion date: May 2023 ➔ Oct 2024

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

Phase I, two-part, multicenter, first-in-human (FIH) study of DS-6000a in subjects with advanced renal cell carcinoma (RCC) and ovarian tumors (OVC). (ASCO 2022) - P1 | "The interim data from dose-escalation of this FIH study showed acceptable tolerability with early signals of efficacy in heavily pretreated pts with advanced RCC and Pt-R OVC, which support further clinical evaluation of DS-6000a in the planned dose-expansion cohorts in advanced RCC and OVC."

Clinical • P1 data • Fatigue • Febrile Neutropenia • Genito-urinary Cancer • Hematological Disorders • Immune Modulation • Inflammation • Neutropenia • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Thrombocytopenia • MUC16 • TOP1

[VIRTUAL] DS-6000a, a novel CDH6-targeting antibody-drug conjugate with a novel DNA topoisomerase I inhibitor DXd, demonstrates potent antitumor activity in preclinical models (ESMO 2021) - P1 | "Based on these preclinical , DS-6000a could provide a valuable therapy with a potential benefit in CDH6-expressing cancers at the clinical setting., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan; E-mail: suzuki.hirokazu.yc@daiichisankyo.co.jp"

Preclinical • Genito-urinary Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor

Trial of DS-6000a Elicits Early Efficacy/Safety Data in RCC and Ovarian Cancer (Targeted Oncology) - P1 | N=110 | NCT04707248 | Sponsor: Daiichi Sankyo, Inc. | "Erika P. Hamilton, MD, lead investigator and director of the Breast and Gynecologic Cancer Research Program at the Sarah Cannon Research Institute/Tennessee Oncology, discusses the findings from a phase 1 trial of DS-6000a in patients with advanced renal cell carcinoma (RCC) and ovarian cancer (NCT04707248)....Nineteen patients had treatment-emergent adverse events (TEAEs), including fatigue (45.5%), nausea (45.5%), and vomiting (27.3%). There were grade 3 or greater TEAEs observed in 4 patients (18.2%) and the most frequent was neutropenia (13.6%). Grade 3 febrile neutropenia was observed in 1 patient and 1 dose-limiting toxicity of grade 4 thrombocytopenia (9.6 mg/kg) also occurred."

P1 data • Genito-urinary Cancer • Gynecologic Cancers • Kidney Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor

Phase 1 Trial Evaluates DS-6000a in RCC and Ovarian Cancer (Targeted Oncology) - "Erika P. Hamilton, MD, discusses the background of a phase 1 trial of DS-6000a in patients with advanced renal cell carcinoma and ovarian cancer....This 2-part, multicenter, first-in-human, phase 1 study will evaluate DS-6000a given as a single agent once every 21 days in patients with platinum resistant ovarian cancer or RCC. In the dose escalation phase of the trial, participants with ovarian cancer and RCC will be enrolled to assess the safety and tolerability of DS-6000a and to determine the maximum tolerated dose for the expansion portion. In the dose expansion portion of the trial, investigators will assess the clinical activity of DS-6000a."

Video

DS-6000a Displays Early Clinical Activity in Ovarian Cancer and RCC (Targeted Oncology) - "In an interview with Targeted Oncology, Erika P. Hamilton, MD, discussed the early clinical activity seen with DS-6000a in patients with advanced ovarian cancer or renal cell carcinoma with disease progression following standard of care treatment....Erika P. Hamilton, MD, and support further evaluation of DS-6000a in the planned dose-expansion cohorts in advanced RCC and ovarian cancer....Hamilton...discussed the early clinical activity seen with DS-6000a in patients with advanced ovarian cancer or RCC with disease progression following standard of care treatment."

Interview

"4 PRs (3 Ov and 1 RCC) with 8 Ov ca pts with CA125 decreases of >=50% with DS-6000a. @SarahCannonDocs" (@MLJohnsonMD2)

Clinical • Renal Cell Carcinoma