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

  • STATUS
    Recruiting
  • End date
    Jan 1, 2024
  • participants needed
    770
  • sponsor
    Daiichi Sankyo Co., Ltd.
Updated on 1 December 2021
cancer
systemic therapy
estrogen
measurable disease
carcinoma
growth factor
squamous cell carcinoma
endocrine therapy
lung cancer
progesterone
hormone therapy
immunohistochemistry
HER2
EGFR
trastuzumab
cancer chemotherapy
solid tumour
solid tumor
triple negative breast cancer
targeted therapy
progesterone receptor
erbb2
epidermal growth factor
estrogen receptor
taxane
platinum-based chemotherapy
lung carcinoma

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.

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.

Details
Condition Non-Small Cell Lung Cancer, Breast Cancer, Diet and Nutrition, Chronic Diarrhea, Skin Wounds, Chronic Shoulder Pain, Vaginal Atrophy, Adverse Effects, Drugs, Injection Port, Breast Cancer - HER2 Positive, Anal Dysplasia, Primary Immunodeficiency, Pediatric Health, Near-Sighted Corrective Surgery, Peripheral Arterial Occlusive Disease, Triple Negative Breast Cancer, Brain Function, Recurrent Respiratory Papillomatosis, Razor Bumps (Pseudofolliculitis Barbae), Metastatic Triple-Negative Breast Cancer, Hormone Receptor Positive Breast Cancer, nsclc
Treatment DS-1062a, Datopotamab Deruxtecan (Dato-DXd)
Clinical Study IdentifierNCT03401385
SponsorDaiichi Sankyo Co., Ltd.
Last Modified on1 December 2021

Eligibility

Yes No Not Sure

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
Additional Inclusion Criteria for NSCLC participants
Has a pathologically documented unresectable advanced NSCLC disease not amenable to curative therapy
Additional Inclusion Criteria for TNBC participants
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)
Additional Inclusion Criteria for HR positive, HER2-negative participants
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
Additional Inclusion Criteria for Small-cell lung cancer (SCLC) participants
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
Additional Inclusion Criteria for Endometrial cancer participants
Pathologically documented recurrent or persistent endometrial cancer that relapsed or progressed after any established and/or curative therapies, including at least 1 systemic therapy
Additional Inclusion Criteria for Pancreatic adenocarcinoma participants
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
Additional Inclusion Criteria for HER2-negative gastroesophageal cancer
participants
Pathologically documented unresectable or metastatic adenocarcinoma of the stomach or esophagus, including the gastroesophagel junction (GEJ) that was previously treated with at least 1 prior line of systemic therapy
No known history of HER2-positivity (defined as Immunohistochemistry IHC 3+ or IHC 2+ and in situ hybridization ISH+) as classified by ASCO-CAP at any time
Additional Inclusion Criteria for Esophageal cancer participants
Pathologically documented unresectable or metastatic squamous cell carcinoma of the esophagus that was previously treated with at least 1 prior line of therapy including platinum-based chemotherapy
Additional Inclusion Criteria for Head and neck squamous cell carcinoma
(HNSCC)
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
participants
Additional Inclusion Criteria for participants with advanced-stage urothelial
cancer
Pathologically documented unresectable, locally advanced or metastatic, urothelial 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 immune checkpoint inhibitor (in combination or sequential)
Additional Inclusion Criteria for Colorectal cancer (CRC) participants
Has not progressed or relapsed within 6 months of therapy with irinotecan
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
Pathologically documented unresectable or metastatic ovarian cancer that
Additional Inclusion Criteria for Platinum-resistant ovarian cancer
Is epithelial ovarian (including less-common histologies per National Comprehensive Cancer Network (NCCN)
participants
Has relapsed or progressed within 6 months of platinum-based chemotherapy
Pathologically documented unresectable or metastatic ovarian cancer that
Is epithelial ovarian (including less-common histologies per NCCN guidelines), fallopian tube, or primary peritoneal presentation
Additional Inclusion Criteria for Platinum-sensitive ovarian cancer
Has relapsed or progressed at least 6 months after the most recent platinum-based chemotherapy
participants
Pathologically documented unresectable or metastatic cervical cancer that relapsed or progressed after at least 1 prior line of systemic therapy
Pathologically documented unresectable or metastatic CRPC that
Additional Inclusion Criteria for Cervical cancer participants
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
Additional Inclusion Criteria for Castration-resistant prostate cancer
participants
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
Objective progression as determined by radiographic progression for participants with measurable disease after androgen deprivation
Additional Inclusion Criteria for Participants with Bacillus Calmette-Guerin
(BCG)-unresponsive (BCGu) High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC)
Histologically confirmed diagnosis of high-risk non-muscle-invasive transitional cell carcinoma of the bladder. Participants with tumors of mixed transitional/non-transitional cell histology are allowed, but transitional cell carcinoma must be the predominant histology. Participants with predominant or exclusively non-transitional cell histology are not allowed
Participants who have papillary tumors (Ta and T1), a complete TURBT must have been performed
Prior treatment with adequate BCG therapy and development of high-risk NMIBC that is unresponsive to BCG therapy
Has elected not to undergo, or is considered ineligible for radical cystectomy, as determined by the treating surgeon
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1, or 2 for BCGu-NMIBC
Receipt of one prior course of checkpoint inhibitor therapy (eg, anti-PD-1 or anti-PD-L1 monoclonal antibody) administered for BCGu-NMIBC is permitted; such participants must have either persistence or recurrence of NMIBC following such therapy

Exclusion Criteria

Has clinically significant corneal disease
Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
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
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
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 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
Uncontrolled or significant cardiac disease including myocardial infarction or uncontrolled/unstable angina within 6 months prior to Cycle 1 Day 1
History of congestive heart failure (New York Heart Association classes II-IV) or uncontrolled or significant cardiac arrhythmia, uncontrolled hypertension(resting systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg)
Has a mean corrected QT interval (QTcF) prolongation to >470 ms based on of the screening triplicate 12-lead ECGs
Has a history of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
Has active human immunodeficiency virus (HIV) infection that is uncontrolled (increasing plasma HIV RNA viral load) with medication, or has an active or uncontrolled hepatitis B and/or hepatitis C infection, is positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis B surface antigen [HBsAg], anti-hepatitis B surface antibody [anti-HBs], anti-hepatitis B core antibody [anti-HBc], or hepatitis B virus [HBV] DNA) and/or hepatitis C infection (as per HCV RNA) within 28 days of Cycle 1 Day 1
Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients of DS-1062a. Has a history of severe hypersensitivity reaction to other monoclonal antibodies
Has leptomeningeal carcinomatosis
Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the participant's participation in the clinical study or evaluation of the clinical study results
Psychological, social, familial, or geographical factors that would prevent regular follow-up. Adults under guardianship, curatorship, safeguard of justice, or family empowerment measure are not eligible
Otherwise considered inappropriate for the study by the investigator
Additional Exclusion Criteria for Participants with BCGu NMIBC
Has muscle invasive (ie, T2, T3, T4) locally advanced non-resectable or metastatic urothelial carcinoma
Has concurrent extra-vesical (ie, urethra, ureter or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
Has undergone any intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/transurethral resection of bladder tumor (TURBT) to starting trial treatment
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