A Study of Dato-DXd in Participants With Solid Tumors [TROPION-PanTumor04 (TP04)]

NCT07890714 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: DS1062-2702024-519729-39-00
• Study Type: interventional
• Target: 268
• Locations: 1 country
• Sites: 1

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.

Conditions

Urothelial Cancer; Non-small Cell Lung Cancer

Keywords

Dato-DXd; TROPION; DS-1062a; Datopotamab Deruxtecan; Trophoblast cell surface protein 2 (TROP2)

Outcome Measures

Primary Outcomes (3)

• Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)

  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.

  During Cycle 1 (cycle length = 21 days)

• Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  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).

  Up to approximately 2.9 years

• Phase 2: Objective Response Rate (ORR) as Assessed by Investigator

  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.

  Up to approximately 2.9 years

Secondary Outcomes (11)

• Phase 1: ORR as Assessed by Investigator

  Up to approximately 2.9 years

• Phase 2: Number of Participants With TEAEs

  Up to approximately 2.9 years

• Phase 1 and 2: Duration of Response (DoR) as Assessed by the Investigator

  Up to approximately 2.9 years

• Phase 1 and 2: Clinical Benefit Rate (CBR) as Assessed by the Investigator

  Up to approximately 2.9 years

• Phase 1 and 2: Disease Control Rate (DCR) as Assessed by the Investigator

  Up to approximately 2.9 years

Study Arms (6)

Sub-study 1: Phase 1: Part 1: Dato-DXd + EV

EXPERIMENTAL

Participants will be administered Dato-DXd, intravenously (IV), along with EV, administered IV.

Drug: Dato-DXd; Drug: Enfortumab Vedotin (EV)

Sub-study 1: Phase 1: Part 2: Dato-DXd + EV + Pembrolizumab

EXPERIMENTAL

Based on the maximum tolerated dose (MTD) determined by Phase 1 Part 1, participants will be administered Dato-DXd, IV, along with EV and pembrolizumab, administered IV.

Drug: Dato-DXd; Drug: Enfortumab Vedotin (EV); Drug: Pembrolizumab

Sub-study 1: Phase 2: Group A: Dato-DXd + EV + Pembrolizumab

EXPERIMENTAL

Participants will be administered Dato-DXd, at recommended Phase 2 dose (RP2D) based on Phase 1 data, along with EV and pembrolizumab, administered IV.

Drug: Dato-DXd; Drug: Enfortumab Vedotin (EV); Drug: Pembrolizumab

Sub-study 1: Phase 2: Group B: EV + Pembrolizumab

ACTIVE COMPARATOR

Participants will be administered EV, IV, along with pembrolizumab, IV.

Drug: Enfortumab Vedotin (EV); Drug: Pembrolizumab

Sub-study 2: Phase 1: Cohort A: Dato-DXd + Olomorasib

EXPERIMENTAL

Participants will be administered Dato-DXd, IV, along with olomorasib, administered orally.

Drug: Dato-DXd; Drug: Olomorasib

Sub-study 2: Phase 2: Dato-DXd + Olomorasib

EXPERIMENTAL

Participants will be administered Dato-DXd along with Olomorasib at RP2D, based on Part 1 data.

Drug: Dato-DXd; Drug: Olomorasib

Interventions

Dato-DXd DRUG

Dato-DXd will be administered as an IV infusion.

Also known as: DS-1062a

Sub-study 1: Phase 1: Part 1: Dato-DXd + EV; Sub-study 1: Phase 1: Part 2: Dato-DXd + EV + Pembrolizumab; Sub-study 1: Phase 2: Group A: Dato-DXd + EV + Pembrolizumab; Sub-study 2: Phase 1: Cohort A: Dato-DXd + Olomorasib; Sub-study 2: Phase 2: Dato-DXd + Olomorasib

Enfortumab Vedotin (EV) DRUG

EV will be administered as IV infusion.

Sub-study 1: Phase 1: Part 1: Dato-DXd + EV; Sub-study 1: Phase 1: Part 2: Dato-DXd + EV + Pembrolizumab; Sub-study 1: Phase 2: Group A: Dato-DXd + EV + Pembrolizumab; Sub-study 1: Phase 2: Group B: EV + Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab will be administered as an IV infusion.

Sub-study 1: Phase 1: Part 2: Dato-DXd + EV + Pembrolizumab; Sub-study 1: Phase 2: Group A: Dato-DXd + EV + Pembrolizumab; Sub-study 1: Phase 2: Group B: EV + Pembrolizumab

Olomorasib DRUG

Olomorasib will be administered as oral capsules.

Sub-study 2: Phase 1: Cohort A: Dato-DXd + Olomorasib; Sub-study 2: Phase 2: Dato-DXd + Olomorasib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• 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.
• 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).
• Has a life expectancy ≥3 months based on investigator's assessment.
• 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.
• 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.

You may not qualify if:

• Has unresolved toxicities from previous anticancer therapy.
• Has spinal cord compression or clinically active central nervous system (CNS) metastases.
• Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients.
• Has uncontrolled or significant cardiovascular disease.
• 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.
• Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
• Has clinically significant corneal disease.
• Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
• Has active or uncontrolled HIV infection.
• Has active or uncontrolled hepatitis B or C virus infection.
• Female participants who are pregnant or breastfeeding or intend to become pregnant.
• Live vaccines within 30 days before the first dose of treatment.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (1)

TCVGH (Taichung Veterans General Hospital)

Taichung, 407219, Taiwan

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

enfortumab vedotin; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Contact for Trial Information

CONTACT

908-992-6400; CTRinfo_us@daiichisankyo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2026
• First Posted: October 22, 2026
• Study Start: October 16, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): January 31, 2030
• Last Updated: October 22, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

TW (1)