Urothelial Cancer, Non-small Cell Lung Cancer
Conditions
Keywords
Dato-DXd, TROPION, DS-1062a, Datopotamab Deruxtecan, Trophoblast cell surface protein 2 (TROP2)
Brief summary
This clinical trial is designed to assess the safety, tolerability, and antitumor activity of Datopotamab Deruxtecan (Dato-DXd) combined with other anticancer agents or as monotherapy in participants with solid tumors.
Detailed description
The study includes 2 independent substudies, which have been defined by tumor type as follows: 1. Sub-protocol 1 Urothelial Cancer (UC) - Cohort A: Dato-DXd plus enfortumab vedotin (EV) with and without pembrolizumab in participants with locally advanced (LA)/metastatic (m) UC (LA/mUC). 2. Sub-protocol 2 kirsten rat sarcoma viral oncogene-mutant-non-small cell lung cancer (KRAS-mutant NSCLC) - Cohort A: Dato-DXd in combination with KRAS G12C inhibitor, olomorasib in participants with LA/mNSCLC. Each sub-study will be conducted in 2 phases: Dose finding (Phase 1) and signal finding (Phase 2).
Interventions
DRUGDato-DXd
Dato-DXd will be administered as an IV infusion.
EV will be administered as IV infusion.
DRUGPembrolizumab
Pembrolizumab will be administered as an IV infusion.
DRUGOlomorasib
Olomorasib will be administered as oral capsules.
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Must consent to provide archival tumor tissue sample or newly obtained pretreatment biopsy if clinically feasible and at an acceptable risk as determined by the investigator. 2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 assessed no more than 14 days prior to Cycle 1 Day 1 (C1D1) (randomization for randomized cohort). 3. Has adequate organ and bone marrow function as assessed by local laboratory within 7 days prior to C1D1 (randomization for randomized cohort) as defined in the protocol. 4. Has a left ventricular ejection fraction (LVEF) ≥50 percent (%) by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) scan within 28 days before C1D1 (randomization for randomized cohort). 5. Has a life expectancy ≥3 months based on investigator's assessment. 6. Female participants must not be pregnant, does not plan to breastfeed during the trial intervention period, agrees to adhere to a contraceptive method that is highly effective and agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during the intervention period. 7. Male participants who intend to be sexually active with a female partner of childbearing potential should use additional barrier methods of contraception or avoid intercourse. Male participants must not freeze or donate sperm at any time during this study. Key
Exclusion criteria
1. Has unresolved toxicities from previous anticancer therapy. 2. Has spinal cord compression or clinically active central nervous system (CNS) metastases. 3. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients. 4. Has uncontrolled or significant cardiovascular disease. 5. Has a history of non-infectious interstitial lung disease (ILD)/pneumonitis, including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected interstitial lung disease (ILD)/pneumonitis that cannot be ruled out by imaging at screening. 6. Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses. 7. Has clinically significant corneal disease. 8. Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection. 9. Has active or uncontrolled HIV infection. 10. Has active or uncontrolled hepatitis B or C virus infection. 11. Female participants who are pregnant or breastfeeding or intend to become pregnant. 12. Live vaccines within 30 days before the first dose of treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) | During Cycle 1 (cycle length = 21 days) | DLTs are defined as the events pre-specified in the protocol and which are not clearly due to the underlying disease or extraneous causes. Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. |
| Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to approximately 2.9 years | An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are defined as those AEs with start or worsening date during the on-treatment period (from the start date of trial intervention to 35 days \[28 (+7) days\] after the last dose date of trial intervention). |
| Phase 2: Objective Response Rate (ORR) as Assessed by Investigator | Up to approximately 2.9 years | Objective response rate (ORR) is defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as assessed by the investigator per RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: ORR as Assessed by Investigator | Up to approximately 2.9 years | ORR is defined as the percentage of participants with a BOR of confirmed CR or confirmed PR, as assessed by the investigator per RECIST v1.1. |
| Phase 2: Number of Participants With TEAEs | Up to approximately 2.9 years | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are defined as those AEs with start or worsening date during the on-treatment period (from the start date of trial intervention to 35 days \[28 (+7) days\] after the last dose date of trial intervention). |
| Phase 1 and 2: Duration of Response (DoR) as Assessed by the Investigator | Up to approximately 2.9 years | DoR is defined as the time (in months) from the date of initial response (CR or PR) to the earlier date of the first objective documentation of radiographic disease progression or death due to any cause. |
| Phase 1 and 2: Clinical Benefit Rate (CBR) as Assessed by the Investigator | Up to approximately 2.9 years | CBR is defined as the percentage of participants with a BOR of confirmed CR, confirmed PR, or stable disease (SD) lasting ≥183 days, as assessed by the investigator per RECIST v1.1. |
| Phase 1 and 2: Disease Control Rate (DCR) as Assessed by the Investigator | Up to approximately 2.9 years | DCR is defined as the percentage of participants with a BOR of confirmed CR, confirmed PR, or SD as assessed by the investigator per RECIST v1.1. |
| Phase 1 and 2: Time to Response (TTR) as Assessed by the Investigator | Up to approximately 2.9 years | TTR is defined as the time (in months) from the start date of trial intervention (randomization for randomized cohort) to the date of the first documentation of objective response in responders (BOR of confirmed CR or confirmed PR as assessed by the investigator per RECIST v1.1). |
| Phase 1 and 2: Best Percentage Change in the SoD of Measurable Tumors as Assessed by Investigator | Up to approximately 2.9 years | The best percentage change in SoD as assessed by the investigator per RECIST v1.1, defined as the percentage change in the smallest SoD from all postbaseline tumor assessments, taking as reference the baseline SoD. |
| Phase 1 and 2: Progression-free Survival (PFS) as Assessed by the Investigator | Up to approximately 2.9 years | PFS is defined as the time (in months) from the start date of trial intervention (randomization for randomized cohort) to the earlier date of the first objective documentation of radiographic disease progression as assessed by investigator per RECIST v1.1 or death due to any cause. |
| Phase 1 and 2: Overall Survival (OS) | Up to approximately 2.9 years | OS is defined as the time (in months) from the start date of trial intervention (date of randomization for randomized cohort) to the date of death due to any cause. |
| Phase 1 and 2: Plasma Concentration of Dato-DXd, Total Anti-TROP2 Antibody and MAAA-1181a | Pre-dose and at multiple timepoints post-dose from Cycle 1 up to Cycle 8 (each cycle=21 days) | — |
| Phase 1 and 2: Percentage of Participants With Positive Anti-drug Antibodies (ADAs) | Up to approximately 2.9 years | — |
Countries
Taiwan
Contacts
CONTACTContact for Trial Information
Outcome results
None listed