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

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ClinicalTrials.gov Identifier: NCT03401385
Recruitment Status : Recruiting
First Posted : January 17, 2018
Last Update Posted : October 5, 2021
Sponsor:
Collaborators:
Daiichi Sankyo, Inc.
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Hormone Receptor Positive Breast Cancer Triple Negative Breast Cancer Non-small Cell Lung Cancer Drug: DS-1062a Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 770 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Single group, but in two study parts, therefore two sequential arms are identified
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : January 31, 2018
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : January 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation - All Participants
All participants enrolled in the dose escalation part
Drug: DS-1062a
A total anti-TROP2 antibody and MAAA-1181a
Other Name: Study treatment

Experimental: Dose Expansion - All Participants
All participants enrolled in the dose expansion part
Drug: DS-1062a
A total anti-TROP2 antibody and MAAA-1181a
Other Name: Study treatment




Primary Outcome Measures :
  1. Number of participants with dose-limiting toxicities [ Time Frame: Within 8 cycles (each cycle is 21 days) ]
    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.

  2. Number of participants with adverse events (AEs) [ Time Frame: When all participants have either discontinued the study or the last participant enrolled in the study has completed at least 6 months of follow up (approximately 4 years) ]

Secondary Outcome Measures :
  1. Maximum concentration (Cmax) [ Time Frame: Within 8 cycles (each cycle is 21 days) ]
    Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a

  2. Time at which Cmax is reached (Tmax) [ Time Frame: Within 8 cycles (each cycle is 21 days) ]
    Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a

  3. Area under the drug concentration-time curve (AUC) to the last observable concentration (AUClast) [ Time Frame: Within 8 cycles (each cycle is 21 days) ]
    Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a

  4. AUC during the dosing period (AUCtau) [ Time Frame: Within 8 cycles (each cycle is 21 days) ]
    Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a

  5. Minimum observed concentration (Ctrough) [ Time Frame: Within 8 cycles (each cycle is 21 days) ]
    Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03401385


Contacts
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Contact: (For Asia sites only) Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111(M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp
Contact: (For US sites) Daiichi Sankyo Contact for Clinical Trial Information 908-992-6400 CTRinfo@dsi.com

Locations
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United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Principal Investigator         
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Principal Investigator         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Principal Investigator         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Principal Investigator         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37205
Contact: Principal Investigator         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Principal Investigator         
Next Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Principal Investigator         
START Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Principal Investigator         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Principal Investigator         
Japan
The Cancer Institute Hospital of Japanese Foundation For Cancer Research Recruiting
Koto-Ku, Tokyo, Japan, 135-8550
Contact: Principal Investigator         
National Cancer Center Hospital Recruiting
Chuo Ku, Japan, 104-0045
Contact: Principal Investigator         
National Cancer Center Hospital East Recruiting
Kashiwa, Japan, 277-8577
Contact: Principal Investigator         
Showa University Hospital Recruiting
Tokyo, Japan, 142-0064
Contact: Principal Investigator         
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Daiichi Sankyo, Inc.
AstraZeneca
Investigators
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Study Director: Global Team Leader Daiichi Sankyo, Inc.
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Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT03401385    
Other Study ID Numbers: DS1062-A-J101
173812 ( Registry Identifier: JAPIC CTI )
First Posted: January 17, 2018    Key Record Dates
Last Update Posted: October 5, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
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.
URL: https://vivli.org/ourmember/daiichi-sankyo/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Hormone Receptor Positive Breast Cancer
Triple Negative Breast Cancer
Non-small Cell Lung Cancer
Other solid tumors
Additional relevant MeSH terms:
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Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms