Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

U3-1565

Antineoplastic Agents, Immunological

Dose escalation of U3 1565 will follow a modified 3+3 study design with a starting intravenous (IV) dose of 2 mg/kg. A maximum of 2 new subjects will receive their first dose of U3-1565 per 24-hour period during the dose-escalation phase. Subsequent escalating doses of 8, 16, and 24 mg/kg are planned. Three to 6 subjects will be enrolled in 4 sequential dose level cohorts.

For Part 2a, 6 or 12 subjects with advanced solid malignant tumors will be enrolled and treated at the MTD or MAD to further define the safety and tolerability of U3-1565. These additional subjects are expected to permit the detection of relatively rare toxicities that would not likely be observed during the dose escalation part of the study, whose 3+3 design implies a maximum of 6 subjects only will be treated at the MTD or MAD. Six subjects will be treated; however, if toxicities meeting the definition of DLT are observed during the first cycle of treatment, 6 more subjects will be treated for a total of 12 subjects.

For Part 2b, up to 30 subjects with advanced solid malignant tumors, with a preference for those with advanced ovarian cancer, will be enrolled and treated at the MTD or MAD. This number of subjects should allow demonstrating U3-1565 has anti-tumor impact by showing treatment-induced changes in pharmacodynamic biomarkers and clinical activity. Ovarian cancer may be more likely to be impacted by U3 1565 than other tumors, considering that in this cancer, high levels of HB-EGF have been associated with an unfavorable clinical outcome. Six subjects will be initially treated; at which point, a safety analysis will be conducted after these initial subjects have completed the first cycle of treatment, to allow the reevaluation of the appropriateness of the dosing level.

U3 1565 will be provided as a sterile, frozen solution. Each glass vial will contain 1.1 mL (1 mL extractable) of study medication with a concentration of 100 mg/mL. U3 1565 will be diluted in a final volume of 100 mL and administered by continuous IV infusion over 60 minutes. Infusion times can be extended to a maximum of 120 minutes for subjects unable to tolerate the 60 minute infusion.

Giorgio Senaldi, MD, PhD

This is a Phase 1, open label study to assess the safety and tolerability of U3 1565, determine maximum tolerated dose (MTD) or establish maximum administered dose (MAD) safety and tolerability.

This study will be conducted in 2 phases: a dose-escalation phase corresponding to Part 1 and a dose-expansion phase articulated in 2 concomitant parts (i.e., Parts 2a and 2b).

All parts of this study are single arm and open label. In all parts, tumor assessments will be performed at screening and every 3 cycles thereafter, while the subject remains on study. U3-1565 clinical activity will be assessed measuring tumor response by physical examination and imaging according to RECIST version 1.1, if applicable.

Study to Assess the Safety and Tolerability of U3-1565 in Subjects With Advanced Solid Malignant Tumors

Phase 1, Open Label Study to Assess the Safety and Tolerability of U3 1565 in Subjects With Advanced Solid Malignant Tumors

Number (percent) of subjects experiencing adverse events (AEs) after treatment with U3-1565

Changes in pharmacodynamic biomarkers in blood and other body fluid specimens (such as soluble HB-EGF and CA125 in serum and ascites) and tumor biopsies after U3 1565 treatment.

Daiichi Sankyo

Anti-Arrhythmia Agents

Cardiotonic Agents

Lipid Regulating Agents

Bone Density Conservation Agents

Digoxin

Rosuvastatin Calcium

Calcium

Calcium, Dietary

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Enzyme Inhibitors

Protective Agents

Single dose of digoxin 0.5 mg (2 tablets 0.25 mg) orally without and with regorafenib

Single dose of rosuvastatin 5mg (1 tablet 5 mg) without and with regorafenib 160 mg q.d. (4 tablets 40 mg)

Rosuvastatin

Once daily orally 160 mg (4 tablets 40 mg)

Regorafenib (Stivarga, BAY73-4506)

Bayer Study Director

Evaluate the effect of regorafenib on the pharmacokinetics of digoxin (P-gp substrate : P-glycoprotein) and rosuvastatin (BCRP substrate: Breast cancer resistant protein) by comparing their Area under time curve (AUC(0-24)) and maximum drug concentration (Cmax) on Day -7 and Cycle 1 or Cycle 2 Day 15 of regorafenib in cancer patients

Effect of Regorafenib on Digoxin and Rosuvastatin in Patients With Advanced Solid Malignant Tumors.

A Phase I, Multi-center, Non-randomized, Open Label, Drug-drug-interaction Study to Determine the Effect of Multiple Doses of Regorafenib (BAY 73-4506) on the Pharmacokinetics of Probe Substrates of Transport Proteins P-gp (Digoxin; Group A) and BCRP (Rosuvastatin; Group B) in Patients With Advanced Solid Malignant Tumors

Bayer

This study will follow a modified Continual Reassessment Method (mCRM) + Escalation with Overdose Control (EWOC),design with a starting intravenous (IV) dose of 0.1 mg/kg.

starting intravenous (IV) dose of 0.1 mg/kg.

DS-1123

Global Clinical Leader

This is an open-label study to evaluate the safety, tolerability, and pharmacokinetics of DS-1123a in Japanese subjects with advanced solid tumors.

Study of DS-1123a in Advanced Solid Tumours

Phase 1, Open-label Study to Assess the Safety, Tolerability, and Pharmacokinetics of DS-1123a in Subjects With Advanced Solid Tumors

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

DS-1123a antibody on Cycle 1: Days 1,15; Cycles 2 and on: Day 1, Stop date, final follow-up date

Change in DS-1123a biomarkers Cytokines expression on Cycle 1: Days 1, 2, 15, 16; Cycle 2: Days 1, 2

Daiichi Sankyo Co., Ltd.

DS-6051b

This is a Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of DS-6051b in Japanese subjects with advanced solid malignant tumors harboring either a ROS1 or NTRK fusion gene.

This study is single arm study with DS-6051b in approximately 9 subjects with advanced solid malignant tumors harboring either a ROS1 or NTRK fusion gene. Safety and tolerability, pharmacokinetics (PK), maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) and preliminary efficacy of DS-6051b will be evaluated.

Phase 1 Study of DS-6051b in Japanese Subjects With Advanced Solid Malignant Tumors

Phase 1 Study of DS-6051b in Japanese Subjects With Advanced Solid Malignant Tumors Harboring Either a ROS1 or NTRK Fusion Gene

number and severity of treatment emergent adverse events

Maximum concentration (Cmax), time to maximum plasma concentration (Tmax), area under the concentration-time curve (AUC) and CL/F for DS-6051a (a free base form of DS-6051b) will be assessed on Days 1 and 15 of Cycle 1.

to determine maximum tolerated dose/recommended phase 2 dose

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Assess the Safety and Tolerability of U3-1565 in Subjects With Advanced Solid Malignant Tumors	NCT01290471	Advanced Solid ... Advanced Ovaria...	U3-1565	18 Years -	Daiichi Sankyo
Effect of Regorafenib on Digoxin and Rosuvastatin in Patients With Advanced Solid Malignant Tumors.	NCT02106845	Neoplasms	Digoxin Rosuvastatin Regorafenib (St...	18 Years -	Bayer
Study to Assess the Safety and Tolerability of U3-1565 in Subjects With Advanced Solid Malignant Tumors	NCT01290471	Advanced Solid ... Advanced Ovaria...	U3-1565	18 Years -	Daiichi Sankyo
Study of DS-1123a in Advanced Solid Tumours	NCT02690337	Advanced Solid ...	DS-1123	20 Years -	Daiichi Sankyo
Phase 1 Study of DS-6051b in Japanese Subjects With Advanced Solid Malignant Tumors	NCT02675491	Advanced Solid ...	DS-6051b	20 Years -	Daiichi Sankyo

Spots Global Cancer Trial Database for advanced solid malignant tumors