REJOICE-PanTumor01: A Phase 2, Multicenter, Open-Label, Pan-Tumor Trial to Evaluate Efficacy andSafety of Raludotatug Deruxtecan (R-DXd) in Participants with Advanced/Metastatic Solid Tumors
A Study of Raludotatug Deruxtecan in ParticipantsWith Advanced/Metastatic Solid Tumors (REJOICE-PanTumor01)
Inoguchi Akihiro
Daiichi Sankyo Co., Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-362251111
dsclinicaltrial@daiichisankyo.co.jp
Contact for Clinical Trial Information
Daiichi Sankyo Co., Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-362251111
dsclinicaltrial@daiichisankyo.co.jp
Pending
Dec. 02, 2024
200
Interventional
non-randomized controlled trial
open(masking not used)
uncontrolled control
single assignment
treatment purpose
Inclusion Criteria
Participants must meet all of the following criteriato be eligible for enrollment into the trial:
1. Sign and date the ICF prior to the start of any trial-specific qualification procedures.
2. 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.
3. Participants must have at least 1 lesion, not reviously irradiated, amenable to biopsy, and must consent to provide a pre-treatment biopsy from a primary and/or metastatic lesion.
4. Has at least 1 measurable lesion evaluated by computed tomography (CT) or magnetic resonanceimaging (MRI) according to RECIST version 1.1 perinvestigator assessment.
5. Participants must have progressed radiologically on or after their most recent line of systemic therapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
7. Required baseline local laboratory data (within14 days prior to the first administration of trial intervention) as specified in the protocol.
8. Additional inclusion criteria for endometrial cancer cohorta. 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.
9. Additional inclusion criteria for cervical cancer cohorta. 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.
10. Additional inclusion criterion for non-HGSOC cohorta. Pathologically or cytologically documented unresectable or metastatic CCOC, low grade endometrioid, low-grade serous, or mucinous OVC that waspreviously treated with at least 1 prior line of therapy.
11. Additional inclusion criteria for urothelial cancer cohort
a. Pathologically or cytologically documented unresectable or metastatic urothelial carcinoma of thebladder, renal pelvis, ureter, or urethra. Histological variants are allowed if urothelial histology is predominant.
b. Relapsed or progressed after treatment with >=1prior line of therapy (maximum of 3) that containsanti-PD-(L)1 therapy in the perioperative or metastatic setting. At least 1 line of therapy must also contain one of the following treatment modalities: chemotherapy or EV. Prior fibroblast growth factorreceptor-inhibitor treatment for those who are eligible is allowed.
*Required treatments can be given in combination or sequentially.
*Prior cisplatin-based therapy or PD-(L)1 therapygiven for the treatment of muscle invasive urothelial carcinoma is counted as 1 line of therapy.
*The same regimen administered twice in different disease settings will be counted as 1 line of prior therapy.
*A minimum of 20 participants in the 2L settingwho have previously received EV and pembrolizumab in combination will be enrolled.
12. ccRCC cohorta. 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.
13. A female participant of childbearing potential(POCBP) is eligible to participate if the following conditions are met:
*Participant is not pregnant as confirmed by highly sensitive pregnancy test.
*Participant does not breastfeed during the trial intervention period and for at least 7 months afterlast dose of trial intervention.
*Participant agrees to adhere to a contraceptivemethod that is highly effective and agrees not todonate eggs (ova, oocytes) to others or freeze/store eggs during the intervention period and for at least the time needed to eliminate the trial intervention after the last dose. The length of time required to continue contraception after last dose for the trial intervention is 7 months.
*Male partners of POCBP (using hormonal contraception) that are capable of producing sperm should use additional barrier methods of contraception for the duration of treatment intervention anduntil 7 months following the last dose of trial intervention.
14. A male participant capable of producing sperm is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate the trial intervention. The length of time required to continue contraception after last dose for the trial intervention is4 months.
*Avoid donating sperm.
*Adhere to either of the following contraceptionmethods:
-True abstinence from penile-vaginal intercourse,when this is in line with the preferred and usual lifestyle of the participant, OR
-Uses a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential PLUS partner use of an additional contraceptive method, as a condom may break or leak
15. Is willing and able to comply with scheduled visits, trial intervention administration plan, laboratory tests, other trial procedures, and trial restrictions.
Participants who meet any of the following criteria will be disqualified from entering the
trial:
1. Inadequate washout period before C1D1 as specified in the protocol.
2. 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.
3. Participants with current bowel involvement/obstruction (including subocclusive disease) related to underlying disease, a history of abdominal fistula, GI perforation, or intraabdominal abscess, or evidence of rectosigmoid involvement by pelvic examination, bowel involvement on CT, or clinical symptoms of bowel obstruction interfering with nutrition.
4. Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
5. Uncontrolled or significant cardiovascular disease as specified in the protocol.
6. 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.
7. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder and any autoimmune, connective tissue, or inflammatory disorder with potential pulmonary involvement or prior pneumonectomy.
8. Chronic steroid treatment (>10 mg/day) with exceptions as noted in the protocol.
9. 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.
10. 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.
11. 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).
12. History of hypersensitivity to any excipients in R-DXd or any known contraindication (included in the approved local labels) to treatment with, including hypersensitivity to, the trial intervention.
13. Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection. Participants with localized fungal infections of skin or nails are eligible.
14. Has active or uncontrolled HIV infection.
15. 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 trial or which would jeopardize compliance with the protocol.
16. Has active or uncontrolled hepatitis B virus infection.
17. Has active or uncontrolled hepatitis C virus infection.
18. Female who is pregnant or breastfeeding or intends to become pregnant during the trial.
19. Men who plan to father a child while in the trial and for at least 4 months after the last administration of trial intervention.
20. Psychological, social, familial, or geographical factors that would prevent regular follow-up.
21. 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 participant; alter the absorption, distribution, metabolism, or excretion of the trial intervention; or confound the assessment of trial results.
22. 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 trial intervention.
18age old over
No limit
Both
Advanced / metastatic solid tumors
Participants will receive raludotatug deruxtecan (R-DXd) administered intravenously every 3 weeks (Q3W).
- Objective Response Rate (ORR) as assessed by the investigator (all cohorts except ccRCC)
ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1 criteria.
- Disease Control Rate (DCR) as assessed by the investigator (ccRCC cohort only)
DCR is defined as 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 Participants Reporting Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) (All Cohorts)
- Progression-free Survival (PFS) as Assessed by the Investigator
Progression-free survival (PFS) is defined as the time interval from the start date of trial intervention to the date of radiographic disease progression according to RECIST version 1.1 criteria or death due to any cause, whichever comes first.
- Duration of Response (DoR) as Assessed by the Investigator
Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (CR or PR) that is subsequently confirmed to the date of the first documentation of radiographic disease progression according to RECIST version 1.1 criteria or death due to any cause, whichever occurs first.
- Time to Response (TTR) as Assessed by the Investigator
Time to response (TTR) is defined as the time from the start date of trial intervention to the date of the first documentation of response (CR or PR) that is subsequently confirmed. TTR will be calculated for confirmed responders only.
- Objective Response Rate as Assessed by the Investigator (ccRCC Cohort Only)
Objective response rate (ORR) is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1 criteria.
- Disease Control Rate (DCR) as Assessed by the Investigator (All Cohorts Except ccRCC Cohort)
Disease control rate (DCR) is defined as 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 participants who are Anti-Drug Antibody (ADA)-Positive at any time and who have a treatment-emergent ADA
Daiichi Sankyo Co., Ltd.
Merck Sharp & Dohme LLC
Applicable
The Cancer Institute Hospital of JFCR, Institutional Review Board
3-8-31 Ariake, Koto-ku, Tokyo
Approval
Oct. 02, 2024
Yes
De-identified individual participant data (IPD) on completed studies 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/
Supporting Information:
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (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.
URL: https://vivli.org/ourmember/daiichi-sankyo/
