A Study of Raludotatug Deruxtecan (R-DXd) in Subjects With Platinum-resistant, High Grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Jun 2024 → ongoing

Decision date (initial)

2024-05-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Daiichi Sankyo Inc.

External identifiers

EU CT number

2023-507914-28-00

ClinicalTrials.gov

NCT06161025

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Pharmacogenetic, Pharmacodynamic

Phase 2:
To evaluate BICR-assessed ORR at each dose level of R-DXd
Phase 3:
To evaluate BICR-assessed PFS with R-DXd treatment compared with investigator’s choice of paclitaxel, PLD or topotecan

Conditions and MedDRA coding

Platinum-resistant, high-grade serous ovarian cancer (OVC),high-grade endometrioid OVC, primary peritoneal cancer, or fallopian tube cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration, Pharmaceuticals And Medical Devices Agency

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Sign and date the informed consent form prior to the start of any study-specific qualification procedures
2. Age ≥18 years or the minimum legal adult age (whichever is greater) at the time the informed consent form is signed
3. Participants with histologically or cytologically documented high-grade serous ovarian cancer (OVC), high-grade endometrioid OVC, primary peritoneal cancer, or fallopian tube cancer
4. For Phase 2 (Part A): Subjects must have at least 1 lesion, not previously irradiated, amenable to biopsy, and must consent to provide a pretreatment biopsy and on-treatment biopsy tissue sample (on-treatment biopsy sample not required for the Phase 3 part of the study). Fresh pretreatment biopsy may be waived for subjects who consent to provide an archival tumor tissue sample from a lesion not previously irradiated, performed within 6 months of consent, and performed after treatment with their most recent cancer therapy regimen For Phase 3 (Part B): Subjects must be willing and able to provide most recently collected (within 5 years of signing the ICF) archival tumor samples with sufficient quantity and quality of tissue. Alternatively, if an archival tumor tissue sample is not available, a newly obtained tumor tissue biopsy from at least 1 lesion not previously irradiated and amenable to core needle biopsy must be provided. If a biopsy procedure is required, the subject must have a lesion that can be biopsied at an acceptable clinical risk as judged by the investigator to be eligible for this trial
5. For Phase 2 (Part A): Has received at least 1 but no more than 3 prior systemic lines of anticancer therapy For Phase 3 (Part B): Has received at least 1 but no more than 4 prior systemic lines of anticancer therapy
6. Has platinum-resistant disease. If a subject had only 1 line of platinum therapy, must have received at least 4 cycles of platinum, must have had a best response of not PD, and then progressed between >90 and ≤180 days after the date of the last dose of platinum If a subject had 2 or 4 lines of platinum therapy, must have received at least 2 cycles of platinum and have progressed on or within 180 days after the date of the last dose of platinum Note: Subjects who are primary platinum refractory during front-line treatment (defined as disease that has progressed on or within ≤90 days of the last dose of first line platinum therapy) are excluded.
7. Has had prior poly-ADP ribose polymerase (PARP) inhibitors for participants with documented breast cancer gene mutation (germline and/or somatic), unless the participant is not eligible for treatment with a PARP inhibitor (Not applicable to subjects in the Phase 3 part of the study)
8. If mirvetuximab soravtansine (MIRV) is locally available: has had prior treatment with MIRV for subjects with documented high folate receptor alpha expression, unless the subject is not eligible for treatment with MIRV
9. Has at least 1 measurable lesion evaluated by computed tomography or magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per investigator assessment
10. Eastern Cooperative Oncology Group performance status of 0 or 1
11. Has adequate organ and bone marrow function as assessed by local laboratory within 14 days prior to initiation of study treatment as defined below. Organ and bone marrow function criteria must also be met when laboratory tests are repeated within 3 days of initiation of study treatment as appropriate. Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 2 weeks prior to screening laboratory tests.Adequate organ/bone marrow function is defined in inclusion criterion 11 of the protocol.
12. If the participant is a female of childbearing potential, she must have a negative serum pregnancy test within 72 hours or urine test within 24 hours before the first dose of study drug and must be willing to use highly effective birth control upon enrollment, during the Treatment Period, and for at least the time required to eliminate each study treatment after the last dose. Male partners of subjects with childbearing potential should use additional barrier methods of contraception for the durationof same period. The length of time required to continue contraception for each study treatment is listed in inclusion criterion 12 of the protocol.
13. Female participants must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least the time required to eliminate each study treatment after the last dose, as described in the inclusion criterion 12 of the protocol.
14. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions
15. For Phase 3 (Part B) only: Participants must be eligible for one of the treatments included in the Investigator's choice of chemotherapy arm

Exclusion criteria 20

1. Has clear cell, mucinous, or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline OVC. (Note for Phase 3 [Part B]: seromucinous, low-grade serous carcinoma or ovarian sarcoma, carcinosarcoma and undifferentiated carcinoma are excluded.)
2. For Phase 2 (Part A): 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 or datopotamab deruxtecan). For Phase 3 (Part B): Prior exposure to other CDH6-targeted agents or an ADC containing a topoisomerase I inhibitor.
3. History of hypersensitivity to any excipients in the R-DXd or any known contraindication to treatment with, including hypersensitivity to, the study drug(s)
4. Has an active or uncontrolled human immunodeficiency virus (HIV) infection . Participants must be tested for HIV viral load during the Screening Period if acceptable by local regulations or institutional review boards Further details provided in exclusion criterion 13 of the protocol.
5. Has any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses or active infection, substance abuse) or other factors that, in the investigator's opinion, makes it undesirable for the participant to participate in the study or which would jeopardize compliance with the protocol
6. Has an active or uncontrolled hepatitis B virus (HBV) or hepatitis C infection (HCV). Hepatitis B and Hepatitis C Screening tests are required. Further details provided in exclusion criterion 15 of the protocol.
7. Female who is pregnant or breastfeeding or intends to become pregnant during the study
8. Psychological, social, familial, or geographical factors that would prevent regular follow-up
9. Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participants ; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results
10. Has a history of receiving live-attenuated vaccine (messenger RNA [mRNA] and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention
11. For Phase 3 (Part B) only: Has clinical symptoms or radiographic evidence of intestinal obstruction for the control group
12. Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with untreated and asymptomatic brain metastases or subjects with treated brain metastases who are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy, at the investigator’s discretion. A minimum of 2 weeks must have elapsed between the end of radiotherapy and randomization and there should be no evidence of progression or need for steroid treatment or anticonvulsants for at least 2 weeks prior to randomization.
13. Any of the following within the past 6 months prior to randomization: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event (eg, intestinal ischemia).
14. Uncontrolled or significant cardiovascular disease as defined in exclusion criterion 5 of the protocol.
15. Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
16. Clinically severe pulmonary compromise (ie, requiring any supplemental oxygen) resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement or prior pneumonectomy
17. Chronic steroid treatment (>10 mg/day)
18. History of malignancy other than epithelial OVC, primary peritoneal cancer, or fallopian tube cancer within 3 years prior to enrollment
19. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 Grade ≤1 or baseline
20. For Phase 3 (Part B) only: Has ascites or pleural effusions that require repeated drainage (less than 4 weeks between drainages).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase 2: ORR as assessed by BICR based on RECIST version 1.1 Phase 3: PFS as assessed by BICR based on RECIST version 1.1 or death due to any reason

Investigational products

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

Test 1

Comparator 3

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 19

Locations

9 EU/EEA countries · 57 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 75 files

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

Application history

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