Description:
HER2-positive cancer is a cancer that tests positive for a protein called human epidermal
growth factor receptor 2 (HER2). HER2 promotes the growth of certain cancer cells. This study
will test an experimental drug called DS-8201a that has not been approved by the health
authorities yet.
DS-8201a will be tested for safety in patients with advanced solid malignant tumors that test
positive for HER2. It also will test how DS-8201a moves within the body (pharmacokinetics).
Title
- Brief Title: Study of DS-8201a for Participants With Advanced Solid Malignant Tumors
- Official Title: A Phase 1, Multicenter, Open-label, Single Sequence Crossover Study to Evaluate Drug-drug Interaction Potential of OATP1B/CYP3A Inhibitor on the Pharmacokinetics of DS-8201a in Subjects With HER2-expressing Advanced Solid Malignant Tumors
Clinical Trial IDs
- ORG STUDY ID:
DS8201-A-A104
- NCT ID:
NCT03383692
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| DS-8201a | Experimental product | Cohort 1: DS-8201a + Ritonavir |
| Ritonavir | Norvir | Cohort 1: DS-8201a + Ritonavir |
| Itraconazole | Sporanox, Orungal | Cohort 2: DS-8201a + Itraconazole |
Purpose
HER2-positive cancer is a cancer that tests positive for a protein called human epidermal
growth factor receptor 2 (HER2). HER2 promotes the growth of certain cancer cells. This study
will test an experimental drug called DS-8201a that has not been approved by the health
authorities yet.
DS-8201a will be tested for safety in patients with advanced solid malignant tumors that test
positive for HER2. It also will test how DS-8201a moves within the body (pharmacokinetics).
Detailed Description
The expected time from the first subject's enrollment until the last subject's enrollment is
approximately 8.5 months. The screening period is 28 days and each cycle of treatment is 21
days.
The data for the primary analysis will cutoff after all subjects have either discontinued the
study or completed at least 3 cycles, whichever comes first. After the primary analysis, the
main study will be closed and transition to the extension period.
Depending on the preliminary results of Cohort 1, Sponsor may decide whether Cohort 2 will be
opened or not.
The number of treatment cycles is not fixed in this study. Subjects who continue to derive
clinical benefit from the study drug in the absence of withdrawal of consent, progressive
disease (PD), or unacceptable toxicity may continue the study drug.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Cohort 1: DS-8201a + Ritonavir | Experimental | DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3 | |
| Cohort 2: DS-8201a + Itraconazole | Experimental | DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Itraconazole BID on Day 17 of Cycle 2 until Day 21 of Cycle 3 | |
Eligibility Criteria
Inclusion Criteria:
- Has a pathologically documented unresectable or metastatic solid malignant tumor, with
HER2 expression [immunohistochemistry (IHC) 3+, 2+, or 1+ and/or in situ hybridization
(ISH) +], Next Generation Sequencing, or other analysis techniques as appropriate]
that is refractory to or intolerable with at least one prior systemic chemotherapy
regimen, or for which no standard treatment is available
- Has a left ventricular ejection fraction (LVEF) ≥ 50%
- Has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
Exclusion Criteria:
- Has a contraindication for receiving ritonavir or itraconazole according to the
prescribing information
- Has a medical history of myocardial infarction within 6 months before enrollment or
symptomatic congestive heart failure
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 20 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Cohort 1: Maximum concentration (Cmax) |
| Time Frame: | within 3 months |
| Safety Issue: | |
| Description: | Categories: DS-8201a and MAAA-1181a, with and without ritonavir |
Secondary Outcome Measures
| Measure: | Number of participants who discontinued because of adverse events (AEs) |
| Time Frame: | after all subjects have either discontinued the study or completed at least 4 cycles of the study drug (approximately 8.5 months) |
| Safety Issue: | |
| Description: | AEs include serious AEs, non-serious treatment-emergent AEs (TEAEs) and AEs of special interest (AESIs)
Clinically significant changes in physical examination findings, vital sign measurements, standard clinical laboratory parameters, 12-lead electrocardiogram (ECG) parameters, ECHO cardiography or multiple-gated acquisition (MUGA) scan, ophthalmologic findings and anti-drug antibodies will be recorded as AEs. |
| Measure: | Objective response rate (ORR) |
| Time Frame: | through the end of the trial (approximately 8.5 months) |
| Safety Issue: | |
| Description: | ORR is defined as the percentage of participants who achieve a best overall response of complete response (CR) or partial response (PR) |
| Measure: | Disease control rate (DCR) |
| Time Frame: | through the end of the trial (approximately 8.5 months) |
| Safety Issue: | |
| Description: | DCR is defined as the percentage of participants who achieve the sum of CR rate, PR rate, and stable disease (SD) rate for a minimum of 5 weeks from the first dosing date |
| Measure: | Duration of Response (DoR) |
| Time Frame: | through the end of the trial (approximately 8.5 months) |
| Safety Issue: | |
| Description: | DoR is defined as the length of time response of CR or PR or SD lasted |
| Measure: | Duration of stable disease (SD) |
| Time Frame: | through the end of the trial (approximately 8.5 months) |
| Safety Issue: | |
| Description: | Duration of stable disease is defined as the length of time SD lasted |
| Measure: | Clinical benefit ratio (CBR) |
| Time Frame: | through the end of the trial (approximately 8.5 months) |
| Safety Issue: | |
| Description: | BR is defined as the number of participants who achieved a best overall response of CR or PR or more than 6 months SD |
| Measure: | Time to response (TTR) |
| Time Frame: | through the end of the trial (approximately 8.5 months) |
| Safety Issue: | |
| Description: | TTR is defined as the time it took for the participants to have a response |
| Measure: | Progression free survival (PFS) |
| Time Frame: | through the end of the trial (approximately 8.5 months) |
| Safety Issue: | |
| Description: | Progression-free survival is defined as the length of time the participant survived without the disease getting worse, based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| Measure: | Number of participants with anti-drug antibodies against DS-8201a |
| Time Frame: | through the end of the trial (approximately 8.5 months) |
| Safety Issue: | |
| Description: | A reaction to the drug by the immune system leads to production of antibodies against the drug, called an anti-drug antibody (ADA) |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Daiichi Sankyo Co., Ltd. |
Trial Keywords
- Unresectable or metastatic solid malignant tumors
- Solid malignant tumors
- Oncology
- HER2
- Antibody drug conjugate
- ADC
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