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:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Esophageal Adenocarcinoma
  • Esophageal Squamous Cell Carcinoma
  • Fallopian Tube Carcinoma
  • Gastric Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Adenocarcinoma
  • Primary Peritoneal Carcinoma
  • Prostate Adenocarcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-human Study of DS-1062a for Advanced Solid Tumors (TROPION-PanTumor01)
  • Official Title: Phase 1, Two-part, Multicenter, Open-label, Multiple Dose, First-in-human Study of DS-1062a in Subjects With Advanced Solid Tumors (TROPION-PanTumor01)

Clinical Trial IDs

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

Conditions

  • Hormone Receptor Positive Breast Cancer
  • Triple Negative Breast Cancer
  • Non-small Cell Lung 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 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.

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 and
      triple negative breast cancer (TNBC) who have been refractory to or relapsed from standard
      treatment or for which no standard treatment is available, will be enrolled. In Dose
      Expansion, additional indications (hormone receptor [HR]-positive human epidermal growth
      factor receptor 2 [HER2]-negative breast cancer, small cell lung cancer [SCLC], endometrial
      cancer, pancreatic adenocarcinoma, HER2-negative gastric/gastroesophageal junction [GEJ]
      cancer, esophageal cancer, head and neck squamous cell carcinoma [HNSCC], transitional cell
      carcinoma of the urothelium, colorectal cancer [CRC], platinum-resistant ovarian cancer,
      platinum-sensitive ovarian cancer, cervical cancer, and castration-resistant prostate cancer
      [CRPC]) may be evaluated, if the study treatment demonstrates acceptable safety, tolerability
      and efficacy in NSCLC 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

        All Participants:

          -  Has relapsed or progressed following local standard treatments or for which no
             standard treatment is available.

          -  Consents to provide mandatory pre-treatment tumor tissue samples for the measurement
             of TROP2 and other biomarkers. 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 bone marrow reserve and organ function within 7 days before Cycle 1, Day
             1.

          -  Has an adequate treatment washout period prior to Cycle 1, Day 1.

          -  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 7 months for females and 4 months for males 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 7 months for males and 4 months for males
             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.

          -  Has no prior treatment with antibody drug conjugate with deruxtecan (including
             trastuzumab deruxtecan [T-DXd; DS-8201a] and patritumab deruxtecan [HER3-DXd; U31402])

          -  Has no prior treatment with trophoblast cell surface antigen 2 (TROP2)-targeted
             therapy

        NSCLC participants only:

          -  Has a pathologically documented unresectable advanced NSCLC disease not amenable to
             curative therapy

        TNBC participants only:

          -  Has a pathologically documented advanced/unresectable or metastatic breast cancer with
             HR- (estrogen and progesterone receptor) negative disease and HER2 negative expression
             according to the American Society of Clinical Oncology - College of American
             Pathologists guidelines (ASCO-CAP)

        HR positive, HER2-negative participants only:

          -  Pathologically documented unresectable or metastatic breast cancer that is:

               -  HER2-negative

               -  Positive for estrogen receptor and/or progesterone receptor

               -  Is documented refractory or resistant to endocrine therapy

               -  Was previously treated with a minimum of 1 and a maximum of 3 prior lines of
                  chemotherapy in the advanced/metastatic setting

        Small-cell lung cancer (SCLC) participants only:

          -  Pathologically documented unresectable or metastatic, and/or extensive-stage SCLC that
             was previously treated with 1 to 2 prior lines of therapy including platinum-based
             chemotherapy and immune checkpoint inhibitor

          -  No prior exposure to topotecan

        Endometrial cancer participants only:

          -  Pathologically documented recurrent or persistent endometrial cancer that relapsed or
             progressed after any established and/or curative therapies, including at least 1
             systemic therapy

        Pancreatic adenocarcinoma participants only:

          -  Pathologically documented unresectable or metastatic pancreatic cancer that was
             previously treated with at least 1 prior line of systemic therapy in neoadjuvant,
             adjuvant, locally advanced or metastatic setting

        HER2-negative gastric/GEJ cancer participants only:

          -  Pathologically documented unresectable or metastatic gastric/GEJ adenocarcinoma that
             was previously treated with at least 1 prior line of systemic therapy

          -  No known history of HER2-overexpression (Immunohistochemistry [IHC] 0, IHC 1 or IHC
             2+/ in situ hybridization [ISH]-negative) as classified by ASCO-CAP at any time

        Esophageal cancer participants only:

          -  Pathologically documented unresectable or metastatic esophageal cancer that:

               -  Is squamous or adenocarcinoma

               -  Was previously treated with at least 1 prior line of therapy including
                  platinum-based chemotherapy

        Head and neck squamous cell carcinoma (HNSCC) participants only:

          -  Pathologically documented unresectable or metastatic HNSCC that was previously treated
             with 1-3 prior lines of therapy including platinum and ICI (in combination or
             sequential), in the advanced or metastatic setting

        Transitional cell carcinoma of the urothelium participants only:

          -  Pathologically documented unresectable, locally advanced or metastatic, transitional
             cell carcinoma (transitional cell and mixed transitional/non-transitional cell
             histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and
             urethra) that was previously treated with at least 1 prior line of therapy including
             platinum-based chemotherapy and ICI (in combination or sequential).

          -  Was previously treated with enfortumab vedotin where available

        Colorectal cancer (CRC) participants only:

          -  Pathologically documented unresectable or metastatic CRC that was previously treated
             with, or were not considered candidates for, available therapies including
             fluoropyrimidine-based chemotherapy, an anti-vascular endothelial growth factor
             therapy, and an anti-epidermal growth factor (EGFR) therapy

          -  Has not progressed or relapsed within 6 months of therapy with irinotecan

        Platinum-resistant ovarian cancer participants only:

          -  Pathologically documented unresectable or metastatic ovarian cancer that:

               -  Is epithelial ovarian (including less-common histologies per National
                  Comprehensive Cancer Network (NCCN)

               -  Has relapsed or progressed within 6 months of platinum-based chemotherapy

        Platinum-sensitive ovarian cancer participants only:

          -  Pathologically documented unresectable or metastatic ovarian cancer that:

               -  Is epithelial ovarian (including less-common histologies per NCCN guidelines),
                  fallopian tube, or primary peritoneal presentation

               -  Has relapsed or progressed at least 6 months after the most recent platinum-based
                  chemotherapy

        Cervical cancer participants only:

          -  Pathologically documented unresectable or metastatic cervical cancer that relapsed or
             progressed after at least 1 prior line of systemic therapy

        Castration-resistant prostate cancer participants only:

          -  Pathologically documented unresectable or metastatic CRPC that:

               -  Is adenocarcinoma of the prostate without neuroendocrine differentiation or small
                  cell histology

               -  Is surgically or medically castrated, with testosterone levels of less than 50
                  nanograms per deciliter

               -  Objective progression by RECIST version 1.1 criteria for participants with
                  measurable disease after androgen deprivation

               -  Has relapsed or progressed after at least 1 of the following: abiraterone or
                  enzalutamide

               -  Has relapsed or progressed after at least 1, but not more than 2, cytotoxic
                  chemotherapy regimens for metastatic castration resistant prostate cancer
                  (mCRPC). At least 1 regimen must have contained a taxane. If a specific taxane
                  was used more than once, the regimens containing the same taxane would be
                  considered as 1 regimen in total.

        Exclusion Criteria:

          -  Has a history of malignancy, other than a tumor type specified in the Inclusion
             Criteria, except (a) adequately resected non-melanoma skin cancer, (b) curatively
             treated in situ disease, or (c) 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 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 based on average of
             the screening triplicate 12-lead ECGs.

          -  Has a history of non-infectious ILD/pneumonitis that required steroids, has current
             ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out 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 spinal cord compression or clinically active brain metastases, defined as
             untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to
             control associated symptoms. Participants with clinically inactive brain metastases
             may be included in the study. A minimum of 2 weeks must have elapsed between the end
             of whole brain radiotherapy and study enrollment. 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 a history of severe hypersensitivity reactions to either the drug substances or
             inactive ingredients of DS-1062a.

          -  Has any other medical conditions, including cardiac disease or psychological
             disorders, and/or substance abuse 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.

          -  Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
             including, but not limited to, any underlying pulmonary disorder, or any autoimmune,
             connective tissue or inflammatory disorders with pulmonary involvement, or prior
             pneumonectomy.
      
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 during 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

  • Hormone Receptor Positive Breast Cancer
  • Triple Negative Breast Cancer
  • Non-small Cell Lung Cancer
  • Other solid tumors

Last Updated

March 23, 2021