DS-3201b in Participants With Lymphomas

A Phase 1 Multiple Ascending Dose Study of DS-3201b in Subjects With Lymphomas

DS-3201b is an experimental drug. It is not approved for regular use. It can only be used in clinical research.

Adults with non-Hodgkin lymphoma (NHL) might be able to join this study if their disease:

• has come back after remission
• is not responding to current treatment

This study has three parts:

1. Dose Escalation is to find the safe dose of DS-3201b that adults with advanced NHL can tolerate.

2. Dose Expansion is to:

   • find out how effective DS-3201b is for rare types of NHL
   • collect additional safety data
3. Drug-Drug Interaction (DDI) Cohort (US Only) is to evaluate the effect of DS-3201b on the pharmacokinetics (PK) midazolam and digoxin when co-administered to patients with NHL

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, Malignant; Non-hodgkin Lymphoma
• Intervention / Treatment: Drug: DS-3201b

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 467-8602
      • Nagoya City University Hospital
  • Chiba
    • Kahiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Iwate
    • Morioka-shi, Iwate, Japan, 020-8505
      • Iwate Medical University Hospital
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 890-0064
      • Imamura General Hospital
    • Kagoshima-shi, Kagoshima, Japan, 890-8520
      • Kagoshima University Hospital
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan, 860-8556
      • Kumamoto University Hosipital
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 852-8501
      • Nagasaki University Hospital
  • Okinawa
    • Nakagami-gun, Okinawa, Japan, 903-0215
      • University of the Ryukyus Hospital
  • Tokyo
    • Minato-ku, Tokyo, Japan, 108-8639
      • The Institute of Medical Science, The University of Tokyo
  • Toyko
    • Chuo Ku, Toyko, Japan, 104-0045
      • National Cancer Center Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8064
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30322-1013
      • Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5418
      • Dana-Farber Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medicine
    • New York, New York, United States, 10065-6007
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center and James Cancer Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-5001
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has hematocytological or pathological diagnosis of non- Hodgkin's lymphoma (NHL)
• Has relapsed from or is refractory to standard treatment or no standard treatment is available
• Is the age of majority in their country (18 in the US and 20 in Japan) at the time of informed consent
• Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Has at least one evaluable lesion site (not applicable for the DDI cohort)
• Has preserved organ function based on baseline laboratory data at screening tests
• If of reproductive potential, agrees to avoid harvesting ova or sperm, and to use a protocol-defined form of contraception or avoid intercourse, during and upon completion of the study, and for at least 3 months after the last dose of study drug

• Tumor biopsy collections:

  1. willing to provide archived or fresh tumor tissue samples that are sufficient for comprehensive genomic and/or proteomic analyses at baseline

  2. [US only] willing to provide fresh on-treatment tumor biopsy if deemed acceptable risk by the investigator

     [Japan only] fresh on-treatment tumor biopsy should be performed if deemed acceptable risk by the investigator

  3. willing to provide optional fresh end-of-treatment biopsy

For ATL subjects:

• Has a positive test result for human T-lymphotropic virus type I antibody
• Has ATL subtype classified as acute, lymphomatous, or chronic with poor prognostic factor
• Has diagnosis of relapse (including relapse after partial remission [PR]) or treatment-resistant ATL at the time of informed consent after prior treatment with at least 1 anti-cancer medication regimen

Exclusion Criteria:

• Has been diagnosed with protocol-defined cutaneous T-cell lymphoma or T-cell leukemia. For DDI cohort, CTCL is not exclusionary.
• Has a history or presence of central nervous system (CNS) involvement
• Has a medical history, complication or other malignancy considered inappropriate for participation in the study, or a serious physical or psychiatric disease, the risk of which may be increased by participation in the study
• Has received drugs or other treatments not allowed by the protocol
• History of treatment with other enhancer of zeste (EZH) inhibitors
• Has had allogeneic hematopoietic stem cell transplantation (HTCP) within 90 days before scheduled dosing on Cycle 1 Day 1
• Is pregnant or breastfeeding
• Is otherwise deemed ineligible to participate by the investigator or sub-investigator

DDI Cohort Only:

• Has received following medications within 14 days prior to study drug administration
• Any CYP3A inhibitors/inducers including weak CYP3A inhibitors/inducers, and P-gp inhibitors, midazolam as well as digoxin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DS-3201b	Drug: DS-3201b

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation Period: Number of participants with dose-limiting toxicities (DLTs)	Number of DLT-evaluable participants with protocol-defined DLTs	within 28 days after the initial dose of the study drug
Dose Escalation Period: Maximum concentration (Cmax) of DS-3201	Categories: Cycle 1 Day 1, Cycle 1 Day 15	within the first 28-day cycle
Dose Escalation Period: Time of maximum concentration (Tmax) of DS-3201	Categories: Cycle 1 Day 1, Cycle 1 Day 15	within the first 28-day cycle
Dose Escalation Period: Area under the plasma concentration time curve up to the last quantifiable time (AUClast) for DS-3201		Day 1 of the first 28-day cycle
Dose Escalation Period: Area under the plasma concentration time curve during the dosing interval (AUCtau) for DS-3201		Day 1 of the first 28-day cycle
Dose Escalation Period: Trough (minimum) plasma concentration (Ctrough)		Day 15 of the first 28-day cycle
Dose Escalation Period: Average plasma concentration (Cavg)		Day 15 of the first 28-day cycle
DDI cohort only: Maximum concentration (Cmax) of DS-3201, midazolam, digoxin	Categories: Day -4, Cycle 1 Day 1, Cycle 1 Day 15	within the first 28-day cycle
DDI cohort only: Time of maximum concentration (Tmax) of DS-3201, midazolam, digoxin	Categories: Day -4, Day 0 (for alternate schedule), Cycle 1 Day 1, Cycle 1 Day 15	within the first 28-day cycle
DDI cohort only: Area under the plasma concentration time curve up to the last quantifiable time (AUClast) for DS-3201,midazolam,digoxin	Categories: Day -4, Day 0 (for alternate schedule), Cycle 1 Day 1, Cycle 1 Day 15	within the first 28-day cycle
DDI cohort only: Area under the plasma concentration time curve during the dosing interval (AUCtau) for DS-3201, midazolam, digoxin	Cycle 1 Day 1, Cycle 1 Day 15	within the first 28-day cycle
Number of participants with treatment-emergent adverse events (TEAEs)	TEAEs are systematically collected from lab values, physical exams, and other investigations	through the end of the study (within approximately 5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best overall response, based on international consensus criteria	Best overall response is defined as the percentage of participants who achieved each category as the best response, considering all overall responses assessed at all time points after the start of study treatment. Categories: CR, CRu, PR, SD, RD/PD, UA Categories: Malignant lymphoma, ATL, CTCL	from the start of study treatment to the end of follow-up visit (within 5 years)
Objective response rate (ORR)	ORR is defined as the percentage of participants who were assessed for best overall response, who achieved CR, UCR, or PR	within 5 years
Disease control rate (DCR)	DCR is defined as the percentage of participants who were assessed for best overall response, who achieved a best response of CR, UCR, PR, or SD	within 5 years
Duration of response (DOR)	DOR is defined as the time from the date at which criteria are first met for CR or PR (including CRu for ATL) until the first date that progressive disease is objectively documented.	within 5 years
Progression-free survival (PFS)	PFS is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of disease progression or death due to any cause.	witihn 5 years
Number of participants with malignant lymphoma who achieved each level of therapeutic response per international consensus standards	Categories: Complete remission (CR), Partial remission (PR), Stable disease (SD), Relapsed disease or progressive disease (RD/PD)	through the end of the study (within approximately 5 years)
Number of participants with ATL who achieved each level of therapeutic response per international consensus standards	Categories: CR, Uncertified complete remission (CRu), PR, SD, RD/PD, Unassessable (UA)	through the end of the study (within approximately 5 years)
Number of participants with CTCL who achieved response per 2011 CTCL criteria	Categories: CR,PR,SD,PD,Relapse	through the end of the study (within approximately 5 years)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.
• Collaborators: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2016
• Primary Completion (Actual): December 31, 2022
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: April 4, 2016
• First Submitted That Met QC Criteria: April 4, 2016
• First Posted (Estimate): April 8, 2016

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: B-cell lymphoma; Peripheral T-cell lymphoma (PTCL); Cutaneous T-cell lymphoma (CTCL); Adult T-cell leukemia-lymphoma (ATL)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: DS3201-A-J101; 163173 (Registry Identifier: JAPIC CTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No