En studie av Raludotatug Deruxtecan hos deltakere med avanserte/metastatiske solide svulster (REJOICE-PanTumor01)
REJOICE-PanTumor01: En fase 2, multisenter, åpen etikett, pan-tumor-forsøk for å evaluere effektiviteten og sikkerheten til Raludotatug Deruxtecan (R-DXd) hos deltakere med avanserte/metastatiske solide svulster
This pan-tumor trial is designed as a signal-seeking trial to assess efficacy and safety of raludotatug deruxtecan (R-DXd) monotherapy in locally advanced or metastatic solid tumors with various cadherin-6 (CDH6) expression levels, including gynecological cancers (endometrial cancer, cervical cancer, and non-high-grade serous ovarian cancer) and genitourinary cancers (urothelial cancer and clear cell renal cell carcinoma [ccRCC]).
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
This trial is designed to evaluate the efficacy and safety of R-DXd in locally advanced or metastatic solid tumors with various CDH6 expression levels. Solid tumor types will include gynecological cancers (endometrial cancer, cervical cancer, and non-high-grade serous ovarian cancer) and genitourinary cancers (urothelial cancer and ccRCC).
For all cohorts except ccRCC, the primary endpoint will be objective response rate (ORR) by investigator assessment per RECIST 1.1. For the ccRCC cohort, the primary endpoint will be disease control rate (DCR) by investigator assessment per RECIST 1.1. All cohorts will also have the assessment of safety and tolerability as another primary objective.
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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Leuven, Belgia, 3000
- UZ Leuven Gynaec onco
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Wilrijk, Belgia, 2610
- ZAS Sint-Augustinus
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Copenhagen, Danmark, 2100
- Herlev og Gentofte Hosp
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Georgia
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Marietta, Georgia, Forente stater, 30060
- Northside Hospital
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Michigan
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Ann Arbor, Michigan, Forente stater, 48109
- University of Michigan Comprehensive Cancer Center Michigan Medicine
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New Jersey
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East Brunswick, New Jersey, Forente stater, 08816
- Astera Cancer Care
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New York
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Albany, New York, Forente stater, 12208
- Women's Cancer Care Associates
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New York, New York, Forente stater, 10065
- Memorial Sloan-Kettering Cancer Center
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Westbury, New York, Forente stater, 11590
- Clinical Research Alliance
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Tennessee
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Germantown, Tennessee, Forente stater, 38138
- West Cancer Center and Research Institute
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Texas
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Houston, Texas, Forente stater, 77030
- The University of Texas MD Anderson Cancer Center
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Caen, Frankrike, 14000
- François Baclesse Center
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Dijon, Frankrike, 21079
- Centre Georges-François Leclerc
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Lille, Frankrike, 59 000
- Centre Oscar Lambret
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Lyon, Frankrike, 69008
- Centre Leon Berard
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Paris, Frankrike, 75012
- Grp Hsp Diac Croix Saint Simon
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Plérin, Frankrike, 22190
- Cario - Centre Armoricain de Radiothérapie, Imagerie Médicale Et Oncologie
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Saint-Herblain, Frankrike, 44805
- Ico - Site René Gauducheau
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Toulouse, Frankrike, 31100
- Institut Claudius Regaud
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Villejuif, Frankrike, 94800
- Gustave Roussy
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Catania, Italia, 95126
- AO per lEmergenza Cannizzaro
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Genova, Italia, 16132
- Irccs Ospedale San Martino
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Meldola, Italia, 47014
- IRCCS Dino Amadori - IRST
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Milan, Italia, 20132
- IRCCS San Raffaele
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Milan, Italia, 40121
- Fondazione IRCCS Istituto Nazionale dei Tumori
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Naples, Italia, 80131
- Federico II Hospital
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Terni, Italia, 05100
- Azienda Ospedaliera S Maria
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Akashi, Japan, 13-70
- Hyogo Cancer Center
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Chūōku, Japan, 104-0045
- National Cancer Center Hospital
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Fukuoka, Japan, 811-1395
- National Hospital Organization Kyushu Cancer Center
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Hidaka, Japan, 1397-1
- Saitama Medical University International Medical Center
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Kashiwa, Japan, 277-8577
- National Cancer Center Hospital East
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Kōtoku, Japan
- The Cancer Institute Hospital of Jfcr
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Nagoya, Japan, 464-8681
- Aichi Cancer Centre
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Osaka, Japan, 541-8567
- Osaka International Cancer Institute
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Changsha, Kina, 410013
- Hunan Cancer Hospital
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Shanghai, Kina, 200000
- Shanghai Cancer center
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A Coruña, Spania, 15006
- Hospital Universitario de A Coruña
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Barcelona, Spania, 08035
- Vall d'Hebron University Hospital
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Barcelona, Spania, 08041
- Hospital de Sant Pau
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Madrid, Spania, 28041
- Hospital 12 Octubre
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Madrid, Spania, 28027
- The Clínica Universidad de Navarra Madrid
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Madrid, Spania, 28033
- Md Anderson Cancer Centre
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Málaga, Spania, 29010
- Hospital Universitario Virgen de la Victoria
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Goyang-si, Sør -Korea, 10408
- National Cancer Center
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Seoul, Sør -Korea, 05505
- Asan Medical Center
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Seoul, Sør -Korea, 06351
- Samsung Medical Center
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Seoul, Sør -Korea, 03722
- Severance Hospital
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Participants must meet all of the following criteria to be eligible for enrollment into the trial:
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Adults greater than or equal to ( ≥) 18 years of age on the day of signing the informed consent form (ICF).
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Participants must have at least 1 lesion, amenable to biopsy, and must consent to provide a pre-treatment biopsy from a primary and/or metastatic lesion.
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Has at least 1 measurable lesion according to RECIST version 1.1 per investigator assessment.
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Participants must have progressed radiologically on or after their most recent line of systemic therapy.
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Eastern Cooperative Oncology Group performance status of 0 or 1.
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Adequate organ/bone marrow function.
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Additional inclusion criteria for endometrial cancer cohort:
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Pathologically or cytologically documented endometrial cancer (carcinoma of any histological subtype or carcinosarcoma), irrespective of microsatellite instability (MSI) or mismatch repair status: small cell/neuroendocrine tumors are not allowed even if mixed histology.
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Documented disease progression after having received ≥1 line of therapy (no more than 3), including platinum-based chemotherapy (PBC)-containing systemic treatment and an anti-PD-(L)1 therapy containing regimen (combined or sequential) in the advanced/metastatic setting.
- Neo-adjuvant/adjuvant systemic therapies are counted as 1 line of therapy if there was progression or recurrence within 1 year from the final dose.
- Prior hormonal therapy is not counted as a line of therapy in regard to the maximum allowed lines of treatment.
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Additional inclusion criterion for non-HGSOC cohort:
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Pathologically or cytologically documented unresectable or metastatic CCOC, low-grade endometrioid (Grade2 or lower), low-grade serous (Grade2 or lower), or mucinous OVC, from ovary, fallopian tube or peritoneum origin that was previously treated with at least 1 prior line of therapy.
• Neo-adjuvant/adjuvant systemic therapies are counted as 1 line of therapy if there was progression or recurrence within 1 year from the final dose.
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In Stage 3 only, participants with pathologically or cytologically documented unresectable or metastatic CCOC can be enrolled. Prior line of therapy requirements remains unchanged.
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Participants who meet any of the following criteria will be disqualified from entering the trial:
- Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis.
- Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event (e.g., intestinal ischemia).
- Uncontrolled or significant cardiovascular disease as specified in the protocol.
- Has any history of (noninfectious) interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Clinically severe pulmonary compromise.
- Chronic steroid treatment (greater than [>]10 mg/day prednisone [or equivalent]) with exceptions as noted in the protocol.
- 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.
- 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 (NCI-CTCAE) v 5.0, Grade less than or equal to (≤)1 or baseline.
- Prior exposure to other CDH6-targeted agents or an antibody drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., trastuzumab deruxtecan, datopotamab deruxtecan).
- Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
- Has active or uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: Endometrial Cancer Cohort
Participants with endometrial cancer who will receive raludotatug deruxtecan (R-DXd) administered intravenously every 3 weeks (Q3W). |
IV administration Q3W
Andre navn:
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Eksperimentell: Cervical Cancer Cohort
Participants with cervical cancer who will receive R-DXd administered intravenously Q3W. |
IV administration Q3W
Andre navn:
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Eksperimentell: Non-high-grade Serous Ovarian Cancer
Participants with non-high-grade serous ovarian cancer who will receive R-DXd administered intravenously Q3W. |
IV administration Q3W
Andre navn:
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Eksperimentell: Urothelial Cancer Cohort
Participants with urothelial cancer who will receive R-DXd administered intravenously Q3W. |
IV administration Q3W
Andre navn:
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Eksperimentell: Clear Cell Renal Carcinoma (ccRCC) Cohort
Participants with clear cell renal carcinoma (ccRCC) who will receive R-DXd administered intravenously Q3W. |
IV administration Q3W
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Objective Response Rate as Assessed by the Investigator (All Cohorts Except ccRCC)
Tidsramme: Baseline up to 48 months
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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. |
Baseline up to 48 months
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Disease Control Rate (DCR) as Assessed by the Investigator (ccRCC Cohort Only)
Tidsramme: Baseline up to 48 months
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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. |
Baseline up to 48 months
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Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) (All Cohorts)
Tidsramme: Baseline up to 48 months
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Baseline up to 48 months
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Progression-free Survival (PFS) as Assessed by the Investigator
Tidsramme: Baseline up to 48 months
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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. |
Baseline up to 48 months
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Duration of Response (DoR) as Assessed by the Investigator
Tidsramme: Baseline up to 48 months
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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. |
Baseline up to 48 months
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Time to Response (TTR) as Assessed by the Investigator
Tidsramme: Baseline up to 48 months
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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. |
Baseline up to 48 months
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Objective Response Rate as Assessed by the Investigator (ccRCC Cohort Only)
Tidsramme: Baseline up to 48 months
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ORR is defined as the proportion of participants with a BOR of confirmed CR or PR according to RECIST version 1.1 criteria. |
Baseline up to 48 months
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Disease Control Rate (DCR) as Assessed by the Investigator (All Cohorts Except ccRCC Cohort)
Tidsramme: Baseline up to 48 months
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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. |
Baseline up to 48 months
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Pharmacokinetic Parameter Maximum Concentration (Cmax) of R-DXd
Tidsramme: Cycles 1 and 3 Day 1 predose and end of infusion (EOI), 3 hours (hr), and 5 hr postdose; Cycle 1 Days 8, 15, and 22; Cycle 2 Day 1 predose and EOI postdose; Cycle 4 (and every 2 cycles thereafter) predose, up to 48 months (each cycle is 21 days)
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Cycles 1 and 3 Day 1 predose and end of infusion (EOI), 3 hours (hr), and 5 hr postdose; Cycle 1 Days 8, 15, and 22; Cycle 2 Day 1 predose and EOI postdose; Cycle 4 (and every 2 cycles thereafter) predose, up to 48 months (each cycle is 21 days)
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The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have a Treatment-emergent ADA
Tidsramme: Baseline up to 48 months
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Baseline up to 48 months
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Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- DS6000-126
- 2024-513307-13-00 (Ctis)
- jRCT2031240486 (Registeridentifikator: jRCT)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
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/
IPD-delingstidsramme
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.
Tilgangskriterier for IPD-deling
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.
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
- ICF
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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