Clinical Trials /

First-in-human Study of DS-1062a for Advanced Solid Tumors (TROPION-PanTumor01)

NCT03401385

Description:

This study is one single group of participants with non-small cell lung cancer (NSCLC) who have not been cured by other treatments. It is the first time the drug has been used in humans, and will be in two parts. The primary purpose of the parts are: - Dose Escalation: To investigate the safety and tolerability and to determine the maximum tolerated dose (MTD) and the recommended dose for expansion (RDE) of DS-1062a - Dose Expansion: To investigate the safety and tolerability of DS-1062a in additional solid tumors This study is expected to last approximately 6 years from the time the first participant is enrolled to the time the last subject is off the study. Study sites are located in both the United States and Japan. The number of treatment cycles is not fixed in this study. Participants who continue to benefit from the study treatment may continue, unless: - they withdraw - their disease gets worse - they experience unacceptable side effects.

Related Conditions:
  • Breast Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-human Study of DS-1062a for Advanced Solid Tumors
  • Official Title: Phase 1, Two-part, Multicenter, Open-label, Multiple Dose, First-in-human Study of DS-1062a in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: DS1062-A-J101
  • SECONDARY ID: 173812
  • NCT ID: NCT03401385

Conditions

  • Carcinoma, Non-Small-Cell Lung
  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
DS-1062aStudy treatmentDose Escalation - All Participants

Purpose

This study is one single group of participants with non-small cell lung cancer (NSCLC) who have not been cured by other treatments. It is the first time the drug has been used in humans, and will be in two parts. The primary purpose of the parts are: - Dose Escalation: To investigate the safety and tolerability and to determine the maximum tolerated dose (MTD) and the recommended dose for expansion (RDE) of DS-1062a - Dose Expansion: To investigate the safety and tolerability of DS-1062a This study is expected to last approximately 4 years from the time the first participant is enrolled to the time the last subject is off the study. Study sites are located in both the United States and Japan. The number of treatment cycles is not fixed in this study. Participants who continue to benefit from the study treatment may continue, unless: - they withdraw - their disease gets worse - they experience unacceptable side effects.

Detailed Description

      The dosage strength will change during the study but all participants will receive the same
      study drug. So the study is not a true 2-arm study, it is a 2-part study.

      In both parts, participants with pathologically documented unresectable advanced NSCLC who
      have been refractory to or relapsed from standard treatment or for which no standard
      treatment is available, will be enrolled. Additional solid tumors might be evaluated, if the
      study treatment demonstrates acceptable safety, tolerability and efficacy in NSCLC and/or
      triple negative breast cancer (TNBC) participants. After the primary analysis, the main
      (registered) study will be considered complete, but data will be collected from participants
      who continue receiving study drug.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation - All ParticipantsExperimentalAll participants enrolled in the dose escalation part
  • DS-1062a
Dose Expansion - All ParticipantsExperimentalAll participants enrolled in the dose expansion part
  • DS-1062a

Eligibility Criteria

        Inclusion Criteria:

          -  Has a pathologically documented unresectable advanced NSCLC disease not amenable to
             curative therapy (NSCLC participants only).

          -  Has a pathologically documented advanced/unresectable or metastatic triple negative
             breast cancer (TNBC participants only).

          -  Has relapsed from or is refractory to standard treatment or for which no standard
             treatment is available.

          -  Consents to provide mandatory pre-treatment tumor tissue samples for the measurement
             of recent TROP2 levels by immunohistochemistry and other biomarkers, which means
             either an archived sample following the last treatment or a DS1062a pre-treatment
             biopsy. There is no minimum TROP2 expression level required for inclusion.

          -  Consents to undergo mandatory on-treatment biopsy if clinically feasible and not
             contraindicated at the time of on-treatment biopsy, and consents to provide the tumor
             tissue samples from on-treatment biopsy for the measurement of TROP2 level and other
             biomarkers.

          -  Is aged ≥20 years old in Japan or ≥18 years old in other countries.

          -  Has an Eastern Cooperative Oncology Group performance status 0-1.

          -  Has a left ventricular ejection fraction (LVEF) ≥50% by either an ECHO or MUGA within
             28 days before enrollment.

          -  Has measurable disease based on RECIST version1.1.

          -  Has adequate organ function within 7 days before enrollment.

          -  Has an adequate treatment washout period prior to enrollment.

          -  If of reproductive/childbearing potential, agrees to use a highly effective from of
             contraception or avoid intercourse during and upon completion of the study and for at
             least 4 months after the last dose of study drug, and agrees not to retrieve, freeze
             or donate sperm or ova starting at Screening and throughout the study period, and at
             least 4 months after the final study drug administration.

          -  After being fully informed about their illness and the investigative nature of the
             protocol (including foreseeable risks and possible toxicities), is willing and able
             comply with the protocol and to provide written, ethics committee-approved informed
             consent form before performance of any study-specific procedures or examinations.

          -  Has a life expectancy of ≥3 months.

          -  If the study Sponsor decides to evaluate additional solid tumors, participants must
             satisfy following criteria to be included in the study: Has a pathologically
             documented advanced solid tumor.

        Exclusion Criteria:

          -  Has multiple primary malignancies, except adequately resected non-melanoma skin
             cancer, curatively treated in situ disease, or other solid tumors curatively treated,
             with no evidence of disease for ≥3 years.

          -  Has a history of myocardial infarction or unstable angina within 6 months before
             enrollment.

          -  Has a medical history of symptomatic congestive heart failure (New York Heart
             Association classes II-IV) or a serious cardiac arrhythmia requiring treatment.

          -  Has a mean corrected QT interval (QTcF) prolongation to >470 ms (females) or >450 ms
             (males) based on average of the screening triplicate 12-lead ECGs.

          -  Has clinically significant lung disease or is suspected to have such diseases by
             imaging at Screening.

          -  Has clinically significant corneal disease.

          -  Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.

          -  Has active human immunodeficiency virus infection that is uncontrolled (increasing
             plasma HIV RNA viral load) with medication, or has an active hepatitis B or C
             infection.

          -  Has clinically active brain metastases, defined as untreated and symptomatic, or
             requiring therapy with steroids or anticonvulsants to control associated symptoms.
             Participants with treated brain metastases that are no longer symptomatic and who
             require no treatment with steroids may be included in the study if they have recovered
             from the acute toxic effect of radiotherapy.

          -  Is lactating or pregnant as confirmed by pregnancy tests performed within 7 days
             before enrollment.

          -  Has unresolved toxicities from previous anticancer therapy.

          -  Has a concomitant medical condition that would increase the risk of toxicity, in the
             opinion of the Investigator.

          -  Has known hypersensitivity to either the drug substances or inactive ingredients in
             the drug product.

          -  Has substance abuse or any other medical conditions that would increase the safety
             risk to the participant or interfere with participation of the participant or
             evaluation of the clinical study in the opinion of the Investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose-limiting toxicities
Time Frame:Within 8 cycles (each cycle is 21 days)
Safety Issue:
Description:Dose-limiting toxicities are defined as side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.

Secondary Outcome Measures

Measure:Maximum concentration (Cmax)
Time Frame:Within 8 cycles (each cycle is 21 days)
Safety Issue:
Description:Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Measure:Time at which Cmax is reached (Tmax)
Time Frame:Within 8 cycles (each cycle is 21 days)
Safety Issue:
Description:Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Measure:Area under the drug concentration-time curve (AUC) to the last observable concentration (AUClast)
Time Frame:Within 8 cycles (each cycle is 21 days)
Safety Issue:
Description:Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Measure:AUC to the end of the dosing period (AUCtau)
Time Frame:Within 8 cycles (each cycle is 21 days)
Safety Issue:
Description:Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Measure:Minimum observed concentration (Ctrough)
Time Frame:Within 8 cycles (each cycle is 21 days)
Safety Issue:
Description:Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo Co., Ltd.

Trial Keywords

  • Non-small cell lung cancer
  • NSCLC
  • Other solid tumors
  • TNBC

Last Updated

April 21, 2020