Phase 1, two-part, multicenter, open-label, multiple dose, first-in-human study of DS-1062a in subjects with advanced solid tumors
Phase 1, first-in-human study of DS-1062a in subjects with advanced solid tumors (TROPION-PanTumor01)
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
recruiting
Feb. 06, 2018
890
Interventional
multi center, open-label
treatment purpose
1
All Participants:
1. Has relapsed or progressed following local standard treatments or for which no standard treatment is available.
2. 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.
3. 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.
4. Is aged >=18 years old.
5. Has an Eastern Cooperative Oncology Group performance status 0-1.
6. Has a left ventricular ejection fraction (LVEF) >=50% by either an ECHO or MUGA within 28 days before enrollment.
7. Has measurable disease based on RECIST version1.1.
8. Has adequate bone marrow reserve and organ function within 7 days before Cycle 1, Day 1.
9. Has an adequate treatment washout period prior to Cycle 1, Day 1.
10. 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.
11. 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.
12. Has a life expectancy of >=3 months.
13. Has no prior treatment with antibody drug conjugate with deruxtecan (including trastuzumab deruxtecan [T-DXd; DS-8201a] and patritumab deruxtecan [HER3-DXd; U3-1402]), and/or ifinatamab deruxtecan [I-DXd; DS-7300].) (Note : Subjects in the new HR-positive HER2-low breast cancer and the HER2-positive breast cancer cohorts are required to have prior treatment with T-DXd and are must not have been treated with any other deruxtecan ADC besides T-DXd.)
14. 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 negative disease and HER2 negative expression according to 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 and/or irinotecan
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 gastroesophageal cancer participants only:
- Pathologically documented unresectable or metastatic adenocarcinoma of the stomach or esophagus, including the gastroesophageal junction (GEJ) that was previously treated with at least 1 prior line of systemic therapy in the advanced or metastatic setting.
- No known history of HER2-positivity (defined as IHC 3+ or IHC 2+ and ISH +) as classified by ASCO-CAP at any time
Esophageal cancer participants only:
- 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.
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 the advanced or metastatic setting
Participants with advanced-stage urothelial cancer only:
- Pathologically documented unresectable, locally advanced or metastatic, urothelial carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) that was previously treated with at least 1 prior line of therapy including an ICI.
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 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 as determined by radiographic progression for participants with measurable disease after androgen deprivation
* Has relapsed or progressed after at least 1 of the following: abiraterone, enzalutamide, apalutamide or darolutamide.
* Has at least 1 documented lesion on either a bone scan or a CT/MRI scan.
* CRPC subjects will be chemotherapy-naive.
Additional inclusion criteria for HR-positive HER2-low breast cancer subjects previously treated with T-DXd
-Pathologically documented unresectable or metastatic breast cancer that is:
*HER2-low, defined as IHC 1+ or IHC 2+ / ISH-negative as classified by ASCO-CAP.
*Positive for estrogen receptor and/or progesterone receptor
-Was previously treated with T-DXd in the advanced or metastatic setting
The oral mucositis/stomatitis substudy
- Is competent and able to comprehend, sign, and date both the main study and the oral mucositis/stomatitis addendum ICFs prior to the start of any substudy procedure or assessment
- Is willing to comply with the procedures of the substudy, including keeping a daily questionnaire on oral hygiene and oral mucositis/stomatitis-related symptoms
1. 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.
2. Uncontrolled or significant cardiac disease including myocardial infarction or uncontrolled/unstable angina within 6 months prior to Cycle 1 Day 1.
3. 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).
4. Has a mean corrected QT interval (QTcF) prolongation to >470 ms based on average of the screening triplicate 12-lead ECGs.
5. 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.
6. Has clinically significant corneal disease.
7. Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. Has active human immunodeficiency virus (HIV) infection that is not well controlled.
8. Has an active or uncontrolled hepatitis B and/or hepatitis C infection.
9. 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.
10. Is lactating or pregnant as confirmed by pregnancy tests performed within 7 days before enrollment.
11. Has unresolved toxicities from previous anticancer therapy.
12. Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator.
13. 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.
14. 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.
15. 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.
16. Has leptomeningeal carcinomatosis.
17. 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.
18. 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.
19. Otherwise considered inappropriate for the study by the investigator.
The oral mucositis/stomatitis substudy
1. Has had any prior oral mucositis/stomatitis that did not resolve within 3 months of signing the ICFs
2. Requires oral steroid or steroid nasal spray or inhaler for asthma, chronic obstructive pulmonary disease, or any other reason at the time of randomization
3. Is immuno-suppressed.
a. Requires immunosuppressive drugs at the time of randomization
4. Has oral inflammation or infections, including candidiasis (thrush) at the time of randomization
5. Has a history of severe hypersensitivity reactions or any other contraindication to steroids or other active principles or excipients of the mouthwash
18age old over
No limit
Both
advanced solid tumors
investigational material(s)
Generic name etc : DS-1062a
INN of investigational material : datopotamab deruxtecan (Dato-DXd)
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Dose Escalation Part : IV solution (Once every 3 weeks, initial dose 0.27 mg /kg) Dose Expansion Part : IV solution (Once every 3 weeks and once every 2 weeks, recommended dose for expansion part)
control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -
safety
Dose Escalation Part: To investigate the safety and tolerability and to determine the maximum tolerated dose and the recommended dose for expansion of DS-1062a.
Dose Expansion Part: To investigate the safety and tolerability of DS-1062a.
The oral mucositis/stomatitis substudy
The proportion of subjects with Grade >=2 oral mucositis/stomatitis by 8 weeks
efficacy
pharmacokinetics
other
1. To characterize the pharmacokinetic (PK) properties of DS-1062a, total anti- TROP2 antibody and MAAA-1181a.
2. To investigate the antitumor activity of DS-1062a.
3. To assess the incidence of anti-drug antibodies against DS-1062a.
- Plasma PK endpoints of DS-1062a, total anti-TROP2 antibody and MAAA-1181a
- NCI-CTCAE ver. 5.0
- Plasma anti-drug antibodies samples
The oral mucositis/stomatitis substudy
1. Time to onset of Grade >=2 oral mucositis/stomatitis,
2. Duration of Grade >=2 oral mucositis/stomatitis
3. Proportion of subjects with any grade of oral mucositis/stomatitis
4. Median number of times the mouthwash was used per day
5. Dose modification for DS-1062a in the main study due to oral mucositis/stomatitis.
6. TEAEs, SAEs, and other AESIs (if applicable) associated with the use of the mouthwash
7. Characterize differences in salivary biomarkers between steroid and non-steroid mouthwash subject groups
- Daily questionnaire on oral hygiene and oral mucositis/stomatitis-related symptoms
- Saliva samples
