First-in-human Study of DS-1062a for Advanced Solid Tumors (TROPION-PanTumor01)
- Conditions
- Hormone Receptor Positive Breast CancerNon-small Cell Lung CancerTriple Negative Breast Cancer
- Interventions
- Drug: Datopotamab Deruxtecan (Dato-DXd)Drug: Steroid Containing MouthwashOther: Non-Steroid Containing Mouthwash
- Registration Number
- NCT03401385
- Lead Sponsor
- 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. There will be two parts and a sub-study.
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.
The primary purpose of the sub-study is to compare the effectiveness of steroid versus non-steroid mouthwash as prophylaxis against oral mucositis/stomatitis in participants receiving DS-1062a.
The sub-study is a randomized study that will include approximately 76 participants enrolling into the Dose Expansion part.
- 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, HR-positive HER2-low breast cancer, HER2-positive 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.
In the sub-study, the additional indications listed for Dose Expansion (except for head and neck cancer) may be evaluated.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 890
Not provided
- 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.
- 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 clinically significant corneal disease.
- Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. Has active human immunodeficiency virus (HIV) infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4+ count >350, no history of AIDS-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications. If an HIV infection meets the above criteria, monitoring of viral RNA load and CD4+ count is recommended. Subjects/participants must be tested for HIV during the Screening Period if acceptable by local regulations or an IRB/IEC.
- Has an active or uncontrolled hepatitis B and/or hepatitis 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 a history of severe hypersensitivity reaction to other monoclonal antibodies.
- 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.
- 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 Sub-study:
- Has had any prior oral mucositis/stomatitis that did not resolve within 3 months of signing the ICFs
- Requires oral steroid or steroid nasal spray or inhaler for asthma, chronic obstructive pulmonary disease, or any other reason at the time of randomization
- Requires immunosuppressive drugs at the time of randomization
- Has oral inflammation or infections, including candidiasis (thrush) at the time of randomization
- Has a history of severe hypersensitivity reactions or any other contraindication to steroids or other active principles or excipients of the mouthwash
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion - All Participants Steroid Containing Mouthwash All participants enrolled in the dose expansion part Dose Expansion - All Participants Non-Steroid Containing Mouthwash All participants enrolled in the dose expansion part Dose Escalation - All Participants Datopotamab Deruxtecan (Dato-DXd) All participants enrolled in the dose escalation part Dose Expansion - All Participants Datopotamab Deruxtecan (Dato-DXd) All participants enrolled in the dose expansion part
- Primary Outcome Measures
Name Time Method Number of participants with adverse events (AEs) 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) Number of participants with Grade >/= 2 oral mucositis/stomatitis in Sub-Study At 8 weeks Number of participants with dose-limiting toxicities 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.
- Secondary Outcome Measures
Name Time Method Maximum concentration (Cmax) Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W) Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Time at which Cmax is reached (Tmax) Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W) Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Area under the drug concentration-time curve (AUC) to the last observable concentration (AUClast) Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W) Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
AUC during the dosing period (AUCtau) Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W) Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Minimum observed concentration (Ctrough) Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W) Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Trial Locations
- Locations (18)
START Oncology
🇺🇸San Antonio, Texas, United States
Showa Medical University Hospital
🇯🇵Shinagawa-Ku, Tokyo, Japan
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Johns Hopkins Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Tisch Cancer Institute, Icahn School of Medicine
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Next Oncology
🇺🇸San Antonio, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Aichi Cancer Center
🇯🇵Nagoya, Aichi, Japan
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
🇯🇵Koto-Ku, Tokyo, Japan
National Cancer Center Hospital
🇯🇵Chuo-Ku, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Japan