Recurrent or Metastatic Solid Tumors
Conditions
Keywords
T-DXd, solid tumor, subcutaneous
Brief summary
This dose escalation and dose expansion study was designed to assess the safety, tolerability, PK and efficacy of subcutaneous T-DXd in participants with metastatic solid tumors.
Interventions
DRUGTrastuzumab Deruxtecan
Dose Escalation Part: Trastuzumab Deruxtecan will be administered at escalating doses to determine the RDE. Expansion Part: Trastuzumab Deruxtecan will be administered at RDE.
Sponsors
Daiichi Sankyo
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Adults ≥18 years or the minimum legal adult age (whichever is greater). 2. a) Disease State: If HER2 status is required for eligibility (for all populations), a documented HER2 test result must be available. Breast Cancer: adults with pathologically documented unresectable or metastatic breast cancer HER2-positive BC: have received a prior anti-HER2-based regimen. For HER2-positive BC participants in Part 2 only, prior anti-HER2 based therapy should have been received in either: * the metastatic setting, or * the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. HR-, HER2-low BC: have received a prior systemic cytotoxic therapy in the metastatic setting; or developed disease recurrence during or within 6 months of completing (neo)adjuvant chemotherapy. HR+, HER2-low/ultralow BC: have received previous ET AND an additional line of ET must not be the next line of treatment considered in the participant's best interest. * For participants in Part 2 with HR+ HER-2low/ultralow BC, the following criteria also apply: * had disease progression while receiving 1 previous line of ET with a CDK4/6i and is not expected to benefit from immediate use of a second line of ET, OR * had disease progression on at least 2 previous lines of ET with or without a target therapy such as CDK4/6, mTOR or PI3-K inhibitors) administered for the treatment of metastatic disease * participants may not have received more than 2 prior lines of cytotoxic therapy in the recurrent or metastatic setting. NSCLC, HER2 mut: adults with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, and who have received a prior systemic therapy. b) Part 2 only: At least 1 RECIST 1.1 measurable lesion on CT or MRI. 3. Radiologic or objective evidence of disease progression on or after the last systemic therapy prior to starting trial intervention. Key
Exclusion criteria
1\. Prior treatment with ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor; 4. Medical history of MI within 6 months before enrollment or symptomatic CHF (New York Heart Association class II to IV). Participants with troponin levels above ULN at screening (as defined by the manufacturer), and without any MI-related symptoms should have a cardiologic consultation during the Screening Period to rule out MI. 5\. Has a corrected QT interval (QTcF) prolongation to \> 480 ms (regardless of participant's sex) based on average of the screening triplicate 12-lead ECG. 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE) | From the start of trial intervention to 21 days after the last dose, up to approximately 9 months | TEAEs are defined as those Adverse Events (AEs) with start or worsening date during the on-treatment period (from the first dose date of trial intervention to 21 days after the last dose date of trial intervention). |
| Area Under Curve (AUC) | From the start of trial intervention to last dose, up to approximately 9 months | — |
| Number of Participants with Dose limiting toxicities (DLT) During the Dose-Escalation Phase | From the start of trial intervention to 21 days after the last dose, up to approximately 9 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Anti-Drug Antibody (ADAs) | From baseline to post-baseline, up to approximately 12 months | — |
| Overall Response Rate (ORR) | From the enrollment/randomization date until documented disease progression, up to 12 months | ORR is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as assessed by investigator per RECIST v1.1 |
| Disease Control Rate (DCR) | From the enrollment/randomization date until documented disease progression, up to 12 months | DCR is defined as the proportion of participants with a BOR of confirmed CR, confirmed PR, or stable disease (SD) per RECIST v1.1. |
Countries
Brazil, France, Japan, South Korea, Spain, Taiwan, United States
Contacts
CONTACTContact for Trial Information
Outcome results
None listed