Phase 2 Pan-Tumor Trial of R-DXd for Advanced/Metastatic Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 May 2025 → ongoing

Decision date (initial)

2025-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo, Inc.

External identifiers

EU CT number

2024-513307-13-00

ClinicalTrials.gov

NCT06660654

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety, Pharmacokinetic

For all cohorts except ccRCC: To evaluate the efficacy of R-DXd treatment measured by ORR as assessed by the investigator

For ccRCC cohort only: To evaluate the efficacy of R-DXd treatment measured by DCR as assessed by the investigator

To assess safety and tolerability of R-DXd

Conditions and MedDRA coding

Advanced/metastatic solid tumors including gynecological cancers (endometrial cancer, cervical cancer, and nonhigh- grade serous ovarian cancer) and genitourinary cancers (urothelial cancer and ccRCC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is >18 years old.
2. Participants must have at least 1 lesion, not previously irradiated, amenable to biopsy, and must consent to provide a pre-treatment biopsy from a primary and/or metastatic lesion.
3. Has at least 1 measurable lesion according to RECIST version 1.1 per investigator assessment.
4. Participants must have progressed radiologically on or after their most recent line of systemic therapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
6. Additional inclusion criteria for endometrial cancer cohort a. Pathologically or cytologically documented endometrial cancer (carcinoma of any histological subtype or carcinosarcoma), irrespective of MSI or mismatch repair status. b. Documented disease progression after having received ≥1 line of therapy (no more than 3), including PBC-containing systemic treatment and an anti-PD-1 therapy containing regimen (combined or sequential) in the advanced/metastatic setting.
7. Additional inclusion criteria for cervical cancer cohort a. Pathologically or cytologically documented recurrent or persistent squamous, adenosquamous, or adenocarcinoma of the uterine cervix. b. Disease progression after having received ≥1 prior line of therapy that includes systemic therapy in the advanced or metastatic setting.
8. Additional inclusion criterion for non-HGSOC cohort a. Pathologically or cytologically documented unresectable or metastatic CCOC, lowgrade endometrioid, low-grade serous, or mucinous OVC that was previously treated with at least 1 prior line of therapy.
9. Additional inclusion criteria for urothelial cancer cohort a. Pathologically or cytologically documented unresectable or metastatic urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Histological variants are allowed if urothelial histology is predominant. b. Relapsed or progressed after treatment with ≥1 prior line of therapy (maximum of 3) that contains anti-PD-(L)1 therapy in the perioperative or metastatic setting.
10. Additional inclusion criterion for the ccRCC cohort a. Pathologically or cytologically documented unresectable or metastatic ccRCC that was previously treated with no more than 3 prior systemic regimens for locally advanced or metastatic RCC, including both a PD-(L)1 checkpoint inhibitor and a VEGF-TKI in sequence or in combination.

Exclusion criteria 11

1. Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis.
2. Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
3. Uncontrolled or significant cardiovascular disease as specified in the protocol.
4. Has a history of (noninfectious) ILD/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
5. Clinically severe pulmonary compromise
6. Chronic steroid treatment (>10 mg/day) with exceptions as noted in the protocol.
7. History of other active malignancy within 3 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (eg, 5-year OS rate >90%) and treated with expected curative outcome .
8. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE Version 5.0, Grade ≤1 or baseline.
9. Prior exposure to other CDH6-targeted agents or an ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan, datopotamab deruxtecan).
10. Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
11. Has active or uncontrolled HIV, HBV or HCV infection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. For all cohorts except ccRCC: ORR is defined as the proportion of participants with a BOR of confirmed CR or confirmed PR according to RECIST version 1.1 criteria.For ccRCC cohort only: DCR is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (maintained for ≥5 weeks) according to RECIST version 1.1. Incidence of TEAEs, SAEs, AESIs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 11

Locations

5 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 83 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications