Dato-DXd in solid tumors (Urothelial Cancer and KRAS-mutant NSCLC) in two sub-studies

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This interventional program includes two sub-studies, each with dose-finding and signal-finding phases. Sub-Protocol 1 investigates Dato-DXd plus enfortumab vedotin, with or without pembrolizumab, in locally advanced or metastatic urothelial cancer. Sub-Protocol 2 tests Dato-DXd in combination with the KRAS G12C inhibitor olomorasib in locally advanced or metastatic KRAS-mutant NSCLC. The study evaluates safety, tolerability, and antitumor activity across solid tumors. Enrollment requires archival tumor tissue when feasible, adequate organ function, good performance status, and other standard eligibility criteria.

Why it matters

Who can join: the full rules

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.

Where it's running

• TCVGH (Taichung Veterans General Hospital)
  Taichung, Taiwan Recruiting

Study contacts

• Study coordinator: Contact for Trial Information
• Email: CTRinfo_us@daiichisankyo.com
• Phone: 908-992-6400

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.