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GEN3014 Sikkerhedsforsøg i recidiverende eller refraktære hæmatologiske maligniteter

27. april 2026 opdateret af: Genmab

Et åbent, multicenter, fase 1/2-forsøg med GEN3014 (HexaBody®-CD38) i recidiverende eller refraktær myelomatose og andre hæmatologiske maligniteter

Lægemidlet, der vil blive undersøgt i undersøgelsen, er et antistof, GEN3014. Da dette er den første undersøgelse af GEN3014 i mennesker, er hovedformålet at evaluere sikkerheden. Udover sikkerhed vil undersøgelsen bestemme den anbefalede GEN3014-dosis, der skal testes i en større gruppe patienter, og vurdere den foreløbige kliniske aktivitet af GEN3014. GEN3014 vil blive undersøgt i recidiverende eller refraktær myelomatose (også kendt som RRMM) og andre blodkræftformer. Studiet består af 3 dele:

  1. Dosiseskaleringen vil teste stigende doser af GEN3014 for at finde et sikkert dosisniveau, der skal testes i de to andre dele.
  2. Udvidelsesdel A vil yderligere teste GEN3014-dosis bestemt ud fra dosiseskaleringsdelen.
  3. Udvidelsesdel B vil sammenligne GEN3014 med daratumumab subkutan (SC), som er et godkendt lægemiddel til RRMM.

Forsøgspersoner vil modtage GEN3014-undersøgelsesbehandling eller daratumumab; ingen vil få placebo. Studievarigheden vil være forskellig for de enkelte deltagere. Samlet set kan undersøgelsen være i gang op til 5 år efter den sidste deltagers første behandling

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Dette forsøg vil blive udført i 3 dele: Dosiseskalering (fase 1), Ekspansionsdele, A og B (fase 2).

Alle deltagere i dosiseskaleringen vil modtage GEN3014, administreret i forskellige dosisniveauer i 28-dages cyklusser. Dosisbegrænsende toksiciteter (DLT'er) vil blive vurderet under den første behandlingscyklus, og den maksimale tolererede dosis (MTD) og/eller den anbefalede fase 2-dosis (RP2D) vil blive bestemt.

I udvidelsesdel A vil GEN3014 blive yderligere evalueret og i yderligere hæmatologiske maligniteter. I udvidelsesdel B vil GEN3014 blive sammenlignet med daratumumab, head-to-head for at evaluere, om GEN3014 kan være mere potent i anti-CD38 mAb-naive RRMM-patienter.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

130

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Australien
      • Epping, Australien
        • Northern Health
      • Melbourne, Australien
        • The Alfred Hospital
      • Sydney, Australien
        • Royal Prince Alfred Hospital
  • Bosnien-Hercegovina
      • Banja Luka, Bosnien-Hercegovina
        • University Clinical Center of the Republic of the Srpska
      • Sarajevo, Bosnien-Hercegovina
        • Klinika za hematologiju KCUS
      • Tuzla, Bosnien-Hercegovina
        • UKC - University Clinical Center Tuzla
  • Danmark
      • Aalborg, Danmark
        • Aalborg Universitet
      • Vejle, Danmark
        • Vejle Hospital
  • Filippinerne
      • Makati City, Filippinerne
        • Makati Medical Center
  • Forenede Stater
    • New Jersey
      • Hackensack, New Jersey, Forenede Stater, 07601
        • John Theurer Cancer Center
    • Ohio
      • Cleveland, Ohio, Forenede Stater, 44106
        • University Hospitals Cleveland Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, Forenede Stater, 53226
        • Medical College of Wisconsin
  • Frankrig
      • Lille, Frankrig
        • CHRU de Lille
      • Nantes, Frankrig
        • CHRU de Nantes
  • Georgien
      • Tbilisi, Georgien
        • ARENSIA Exploratory Medicine LLC
  • Grækenland
      • Athens, Grækenland
        • Alexandra General Hospital
      • Athens, Grækenland
        • Evangelismos Hospital NKUA
      • Rio, Grækenland
        • University General Hospital of Patras
      • Thessaloniki, Grækenland
        • Ahepa University General hospital
  • Holland
      • Maastricht, Holland
        • Maastricht UMC
      • Rotterdam, Holland
        • Erasmus MC
      • Utrecht, Holland
        • UMC Utrecht
  • Malaysia
      • Ampang, Malaysia
        • Hospital Ampang
      • Johor Bahru, Malaysia
        • Hospital Sultanah Aminah
      • Kuching, Malaysia
        • Hospital Umum Sarawak
      • Petaling Jaya, Malaysia
        • Beacon Hospital
  • Moldova
      • Chisinau, Moldova
        • Institute of Oncology, ARENSIA Exploratory Medicine
  • New Zealand
      • Christchurch, New Zealand
        • Christchurch Hospital
      • Grafton, New Zealand
        • Auckland Cancer Trials Centre
      • Palmerston North, New Zealand
        • Palmerston North Hospital
      • Takapuna, New Zealand
        • North Shore Hospital
  • Nordmakedonien
      • Skopje, Nordmakedonien
        • University Clinic of Hematology
  • Polen
      • Gdansk, Polen
        • University Centrum Kliniczne
      • Katowice, Polen
        • Pratia Onkologia Katowice
      • Krakow, Polen
        • Pratia MCM
      • Wroclaw, Polen
        • Wroclaw Medical University
  • Spanien
      • Pamplona, Spanien
        • University of Navarra
      • Salamanca, Spanien
        • University Hospital of Salamanca
  • Sverige
      • Huddinge, Sverige
        • Karolinska Institute
      • Lund, Sverige
        • Universitetssjukhuset i Lund
  • Sydkorea
      • Gwangju, Sydkorea
        • Chonnam National University Hwasun Hospital
      • Pusan, Sydkorea
        • Pusan National University Hospital PNUH
      • Seongnam, Sydkorea
        • Gachon University Gil Medical Center
      • Seoul, Sydkorea
        • Samsung Medical Center
      • Seoul, Sydkorea
        • Seoul National University Hospital
  • Tjekkiet
      • Brno, Tjekkiet
        • Fakultní nemocnice Brno
      • New Town, Tjekkiet
        • Vseobecna Fakultní Nemocnice
      • Nový Hradec Králové, Tjekkiet
        • Fakultni Nemocnice Hradec Kralove FNHK
      • Olomouc, Tjekkiet
        • Fakultni Nemocnice Olomouc (FNOL)
      • Poruba, Tjekkiet
        • FNO - Fakultni nemocnice Ostrava
  • Ukraine
      • Kyiv, Ukraine
        • ARENSIA Exploratory Medicine
  • Ungarn
      • Nyíregyháza, Ungarn
        • Szabolcs-Szatmar-Bereg County Hospitals and University Hospital, Josa Andras University Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

14 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

Nøgleinklusionskriterier

  1. Skal være mindst 18 år.
  2. Skal underskrive en informeret samtykkeformular (ICF) før alle screeningsprocedurer.
  3. Skal have friske knoglemarvsprøver indsamlet ved screening.
  4. Eastern Cooperative Oncology Group (ECOG) præstationsstatus (PS) score 0, 1 eller 2.
  5. Har acceptable laboratorietestresultater i screeningsperioden
  6. En kvinde med reproduktionspotentiale skal acceptere at bruge passende prævention under forsøget og i 12 måneder efter den sidste GEN3014-administration.
  7. En kvinde i den fødedygtige alder skal have et negativt serum beta-humant choriongonadotropin (β-hCG) ved screening.
  8. En kvinde skal acceptere ikke at donere æg (æg, oocytter) til assisteret reproduktion under forsøget og i 12 måneder efter at have modtaget den sidste dosis af GEN3014.

  9. En mand, der er seksuelt aktiv med en kvinde i den fødedygtige alder og ikke har fået foretaget en vasektomi, skal acceptere at bruge en barrieremetode til prævention.

    Specifikt for RRMM:

  10. Skal have dokumenteret myelomatose som defineret af kriterierne nedenfor og have bevis for sygdomsprogression på det seneste tidligere behandlingsregime baseret på IMWG-kriterier:

    • Forudgående dokumentation af monoklonale plasmaceller i knoglemarven

      ≥10 % eller tilstedeværelse af et biopsi-bevist plasmacytom. og

    • Målbar sygdom ved baseline som defineret ved et af følgende:
    • IgG, IgA, IgD eller IgM myelom: Serum M-proteinniveau ≥0,5 g/dL (≥5 g/L) eller urin M-proteinniveau ≥200 mg/24 timer; Eller
    • Let kæde myelom: Serum Ig fri let kæde (FLC) ≥10 mg/dL og unormalt serum Ig kappa lambda FLC ratio Bemærk: Individer med RRMM skal have udtømt standardbehandlinger efter investigators skøn.
  11. For anti-CD38 mAb-naiv RRMM-kohorte: Forsøgspersonen har modtaget mindst 3 tidligere behandlingslinjer inklusive en PI og en IMiD i vilkårlig rækkefølge, eller er dobbelt refraktær over for en PI og en IMiD; eller forsøgsperson modtog ≥ 2 tidligere behandlingslinjer, hvis 1 af disse linjer omfattede en kombination af PI og IMiD. Bemærk: Forsøgspersoner bør ikke have modtaget noget anti-CD38-antistof. Anti-CD38 mAb-naive RRMM-personer vil blive rekrutteret fra lande, hvor anti-CD38-terapier ikke er tilgængelige.

  12. For anti-CD38 mAb-behandlet RRMM-kohorte: Forsøgspersonen har modtaget mindst 2 tidligere behandlingslinjer og skal have seponeret daratumumab eller isatuximab i mindst 4 uger før den første dosis af GEN3014. Bemærk: Forsøgspersoner bør ikke have modtaget noget andet anti-CD38-antistof undtagen daratumumab eller isatuximab.

    Specifikt for AML:

  13. Tilbagefaldende eller refraktær AML, både de novo eller sekundær; må have fejlet al konventionel terapi. Akut promyelocytisk leukæmi (APL) er udelukket fra dette forsøg. Bemærk: Tilbagefald er defineret ved BM-blaster ≥5 % hos patienter, der tidligere har været i CR, eller genkomst af blaster i blodet eller udvikling af ekstramedullær AML. Refraktær er defineret som ikke at kunne opnå en CR efter den indledende behandling.
  14. Person med recidiverende AML, som har modtaget mindst 2 tidligere behandlinger for AML med undtagelse af hydroxyurinstof.
  15. •Forsøgsperson med refraktær AML, som har modtaget mindst 1 tidligere behandlingslinje for AML med undtagelse af hydroxyurinstof.

  16. Forsøgspersonens forventede levetid ved screening vurderes til at være mindst 3 måneder.

    Specifikt for DLBCL

  17. Tilbagefaldende eller refraktær DLBCL, både de novo eller histologisk transformeret. Bemærk: Tilbagefaldende sygdom defineres som tilbagevenden eller vækst af lymfom efter mindst 6 måneders varighed af respons. Refraktær sygdom er defineret som manglende opnåelse af respons efter mindst 2 behandlingscyklusser eller gensyn efter en varighed af respons på
  18. Modtaget mindst 2 tidligere linjer med systemisk terapi, hvor 1 er en CD20-holdig kemoimmunterapi.

  19. Har mindst 1 målbart sygdomssted:

    • En fluorodeoxyglucose (FDG)-positronemissionstomografi (PET) computertomografi (CT)-scanning, der viser positiv læsion, der er kompatibel med CT (eller magnetisk resonansbilleddannelse [MRI])-definerede anatomiske tumorsteder og
    • En CT-scanning (eller MR) med involvering af ≥2 tydeligt afgrænsede læsioner/knuder med lang akse >1,5 cm og kort akse >1,0 cm; eller 1 tydeligt afgrænset læsion/knude med en lang akse >2,0 cm og en kort akse ≥1,0 ​​cm.
  20. Skal have tilgængeligt arkiv eller frisk tumorvæv eller begge dele for at indsendes til et centralt laboratorium for CD38-analyse

Nøgleudelukkelseskriterier

  1. Forudgående behandling med et anti-CD38-antistof undtagen daratumumab eller isatuximab.
  2. Behandling med et anticancermiddel, kemoterapi, strålebehandling eller større operation inden for 2 uger før den første dosis af undersøgelsesbehandlingen.
  3. Behandling med et forsøgslægemiddel inden for 4 uger eller 5 halveringstider, alt efter hvad der er kortest, før den første dosis af undersøgelsesbehandlingen.
  4. Kumulativ dosis af kortikosteroider mere end det, der svarer til ≥140 mg prednison inden for en 2-ugers periode før den første dosis af undersøgelsesbehandlingen.
  5. Har klinisk signifikant hjertesygdom.
  6. Toksiciteter fra tidligere anti-cancer-terapier er ikke forsvundet til baseline-niveauer eller til grad 1 eller mindre bortset fra alopeci og perifer neuropati.
  7. Primær centralnervesystem (CNS) tumor eller kendt CNS involvering ved screening.
  8. Har kendt historie/positiv serologi for hepatitis B
  9. Kendt sygehistorie eller igangværende hepatitis C-infektion, der ikke er blevet helbredt.
  10. HIV-positiv ved screening
  11. Modtager i øjeblikket andre undersøgelsesmidler.
  12. En kvinde, der er gravid eller ammer, eller som planlægger at blive gravid, mens hun er tilmeldt dette forsøg eller inden for 12 måneder efter den sidste dosis af undersøgelsesbehandlingen.

  13. En mand, der planlægger at blive far til et barn, mens han er tilmeldt dette forsøg eller inden for 12 måneder efter den sidste dosis af undersøgelsesbehandlingen.

    Specifikke ekskluderingskriterier for RRMM:

  14. • Tidligere allogen HSCT.

  15. Autolog HSCT inden for 3 måneder efter den første dosis af GEN3014.

    Specifikke ekskluderingskriterier for R/R AML:

  16. •
  17. • Tidligere autolog HSCT.
  18. • Allogen HSCT inden for 3 måneder efter den første dosis af GEN3014.
  19. • Aktiv graft-versus-host-sygdom, der kræver immunsuppressiv behandling. Enhver immunsuppressiv medicin (f.eks. calcineurinhæmmere) skal stoppes ≥4 uger før den første dosis af GEN3014.

BEMÆRK: Andre protokoldefinerede inklusions-/eksklusionskriterier kan være gældende.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Daratumumab

Deltagere i Udvidelse Del B med

- RRMM (anti-CD38 mAb-naiv)
Medicin: Daratumumab
Daratumumab administreres ved subkutane injektioner.
Andre navne:
  • DARZALEX FASPRO®
Eksperimentel: Gen3014

Eksperimentel: Gen3014 Deltagere i dosisoptrapningsfase med

  • RRMM
  • R/R aml

Deltagere i ekspansion del A med

  • RRMM (Anti-CD38 MAB-NAIVE)
  • RRMM (Anti-CD38 MAB-Refractory)
  • R/R DLBCL
  • R/R aml

Deltagere i ekspansionsdel B med

• RRMM (Anti-CD38 MAB-NAIVE)
Biologisk: GEN3014
GEN3014 administreres ved IV-infusion.
Andre navne:
  • HexaBody®-CD38

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)
Tidsramme: 28 days during the first cycle (cycle =28 days)
DLTs were defined as: All Grade 5 toxicities, Grade 4 thrombocytopenia, neutropenia or anemia and Grade 3/4 febrile neutropenia and hemorrhage associated with thrombocytopenia, all non-hematological toxicities of grade ≥3 (with exceptions per protocol), Grade 4 tumor lysis syndrome (TLS), Grade 4 infusion-related reaction (IRR), and any liver toxicity of elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times or greater above the upper limit of normal (ULN) with serum total bilirubin of ≥2 times the upper limit of normal, without findings of cholestasis and in the absence of alternative etiologies. DLTs were graded for severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
28 days during the first cycle (cycle =28 days)
Dose Escalation: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsramme: Up to approximately 4 years 3 months
An AE was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE was defined as an AE that met 1 of the following criteria: fatal or life-threatening, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, was medically significant (jeopardized the participant or may have required medical or surgical intervention to prevent one of the outcomes listed above), required inpatient hospitalization or prolongation of existing hospitalization. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Up to approximately 4 years 3 months
Expansion Part A: Objective Response Rate (ORR)
Tidsramme: Up to approximately 4 years 3 months
ORR was defined as the percentage of participants with a partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria for RRMM participants and based on Lugano criteria for DLBCL participants. Per IMWG criteria, PR was defined as ≥50% reduction of serum M-protein plus reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h. In addition to these criteria, if present at baseline, a ≥50% reduction in the size (sum of the product of the diameters [SPD]) of soft tissue plasmacytomas was also required. Per Lugano criteria, PR was defined as ≥50% decrease in SPD of up to 6 target measurable nodes and extranodal sites, absent/normal, regressed, but no increase in non-measurable lesions, spleen regressed >50% in length beyond normal (13 centimeters [cm]), and no new lesions.
Up to approximately 4 years 3 months
Expansion Part B: ORR
Tidsramme: Up to approximately 4 years 3 months
ORR was defined as the percentage of participants with a PR or better based on IMWG criteria. Per IMWG criteria, PR was defined as ≥50% reduction of serum M-protein plus reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h. In addition to these criteria, if present at baseline, a ≥50% reduction in the size (SPD) of soft tissue plasmacytomas was also required.
Up to approximately 4 years 3 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Dose Escalation and Expansion Part A: Maximum (Peak) Plasma Concentration (Cmax) of GEN3014
Tidsramme: Dose Escalation: Cycle 1 Day 1, Cycle 1 Day 8 (RRMM Dose Escalation: GEN3014 0.2/0.6 mg/kg only), Cycle 2 Day 1, Expansion Part A: Cycle 1 Day 1, Cycle 2 Day 1 (cycle =28 days)
Venous blood samples were collected for analyzing concentrations of GEN3014. For the RRMM Dose Escalation 0.2/0.6 mg/kg arm, the participant underwent intraparticipant dose escalation in Cycle 1, where the participant received 0.2 mg/kg during the first week and 0.6 mg/kg from second week and beyond. Therefore, pharmacokinetic (PK) parameters were additionally calculated for Cycle 1 Day 8 dosing only in the RRMM Dose Escalation 0.2/0.6 mg/kg arm to account for the change in dosing over Cycle 1 in this arm.
Dose Escalation: Cycle 1 Day 1, Cycle 1 Day 8 (RRMM Dose Escalation: GEN3014 0.2/0.6 mg/kg only), Cycle 2 Day 1, Expansion Part A: Cycle 1 Day 1, Cycle 2 Day 1 (cycle =28 days)
Dose Escalation, Expansion Part A and Expansion Part B: Pre-dose (Trough) Concentrations (Ctrough) of GEN3014
Tidsramme: Dose Escalation: Cycle (C) 1 Day (D) 1, C1D8 (RRMM GEN3014 0.2/0.6 mg/kg, R/R AML Dose Escalation), C2D1, Expansion Part A: C1D1, C2D1 (R/R DLBCL Expansion Part A: C1D8 and C2D8) Expansion Part B: C1D1, C1D8, C2D1, C3D1, C7D1, C8D1 (cycle = 28 days)
Venous blood samples were collected for analyzing concentrations of GEN3014. For the RRMM Dose Escalation 0.2/0.6 mg/kg arm, the participant underwent intraparticipant dose escalation in Cycle 1, where the participant received 0.2 mg/kg during the first week and 0.6 mg/kg from second week and beyond. Therefore, PK parameters were additionally calculated for Cycle 1 Day 8 dosing in the RRMM Dose Escalation 0.2/0.6 mg/kg arm to account for the change in dosing over Cycle 1 in this arm.
Dose Escalation: Cycle (C) 1 Day (D) 1, C1D8 (RRMM GEN3014 0.2/0.6 mg/kg, R/R AML Dose Escalation), C2D1, Expansion Part A: C1D1, C2D1 (R/R DLBCL Expansion Part A: C1D8 and C2D8) Expansion Part B: C1D1, C1D8, C2D1, C3D1, C7D1, C8D1 (cycle = 28 days)
Dose Escalation and Expansion Part A: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last) of GEN3014
Tidsramme: Dose Escalation: Cycle 1 Day 1, Cycle 1 Day 8 (RRMM Dose Escalation: GEN3014 0.2/0.6 mg/kg only), Cycle 2 Day 1, Expansion Part A: Cycle 1 Day 1, Cycle 2 Day 1 (cycle =28 days)
Venous blood samples were collected for analyzing concentrations of GEN3014. For the RRMM Dose Escalation 0.2/0.6 mg/kg arm, the participant underwent intraparticipant dose escalation in Cycle 1, where the participant received 0.2 mg/kg during the first week and 0.6 mg/kg from second week and beyond. Therefore, PK parameters were additionally calculated for Cycle 1 Day 8 dosing only in the RRMM Dose Escalation 0.2/0.6 mg/kg arm to account for the change in dosing over Cycle 1 in this arm.
Dose Escalation: Cycle 1 Day 1, Cycle 1 Day 8 (RRMM Dose Escalation: GEN3014 0.2/0.6 mg/kg only), Cycle 2 Day 1, Expansion Part A: Cycle 1 Day 1, Cycle 2 Day 1 (cycle =28 days)
Dose Escalation and Expansion Part A: Area Under the Concentration Time Curve From Zero to 168 Hours (AUC0-168 h) of GEN3014
Tidsramme: Dose Escalation: Cycle 1 Day 1, Cycle 1 Day 8 (RRMM Dose Escalation: GEN3014 0.2/0.6 mg/kg only), Cycle 2 Day 1, Expansion Part A: Cycle 1 Day 1, Cycle 2 Day 1 (R/R DLBCL Expansion Part A: Cycle 1 Day 1 only) (cycle =28 days)
Venous blood samples were collected for analyzing concentrations of GEN3014. For the RRMM Dose Escalation 0.2/0.6 mg/kg arm, the participant underwent intraparticipant dose escalation in Cycle 1, where the participant received 0.2 mg/kg during the first week and 0.6 mg/kg from second week and beyond. Therefore, PK parameters were additionally calculated for Cycle 1 Day 8 dosing only in the RRMM Dose Escalation 0.2/0.6 mg/kg arm to account for the change in dosing over Cycle 1 in this arm.
Dose Escalation: Cycle 1 Day 1, Cycle 1 Day 8 (RRMM Dose Escalation: GEN3014 0.2/0.6 mg/kg only), Cycle 2 Day 1, Expansion Part A: Cycle 1 Day 1, Cycle 2 Day 1 (R/R DLBCL Expansion Part A: Cycle 1 Day 1 only) (cycle =28 days)
Dose Escalation and Expansion Part A: Number of Participants With Anti-Drug Antibodies (ADAs) to GEN3014
Tidsramme: Dose Escalation: Baseline up to a max of approx. 34.5 months, Expansion Part A: Baseline up to a max of approx. 16.6 months
Venous blood samples were drawn for analysis of ADAs to GEN3014.
Dose Escalation: Baseline up to a max of approx. 34.5 months, Expansion Part A: Baseline up to a max of approx. 16.6 months
Dose Escalation: ORR
Tidsramme: Up to approximately 4 years 3 months
ORR was defined as the percentage of participants with a PR or better. The response in RRMM Cohorts was assessed following IMWG criteria 2016. Per IMWG criteria, PR was defined as ≥50% reduction of serum M-protein plus reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h. In addition to these criteria, if present at baseline, a ≥50% reduction in the size (SPD) of soft tissue plasmacytomas was also required.
Up to approximately 4 years 3 months
Dose Escalation and Expansion Part A: Clinical Benefit Rate (CBR)
Tidsramme: Up to approximately 4 years 3 months
CBR was defined as the percentage of participants with a best overall response of minimal response (MR), partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) as determined by the investigator per IMWG response criteria for RRMM participants. MR=≥25% but ≤49% reduction of serum M-protein, reduction of 24-h urine by 50%-89% and if present at baseline, ≥50% reduction in the size (SPD) of soft tissue plasmacytomas. PR=≥50% reduction of serum M-protein, reduction in 24-h urinary M-protein by ≥90% or to <200mg/24h and if present at baseline,≥50% reduction in SPD of soft tissue plasmacytomas. VGPR=Serum+urine M-protein detectable by IFE but not electrophoresis or ≥90% reduction in serum M-protein+urine M-protein level <100mg/24h. CR=Negative IFE on serum/urine + disappearance of soft tissue plasmacytomas and ≤5% plasma cells in bone marrow aspirates. sCR=CR+normal FLC ratio, absence of clonal cells in bone marrow biopsy by IHC.
Up to approximately 4 years 3 months
Dose Escalation, Expansion Part A and Expansion Part B: Duration of Response (DOR)
Tidsramme: Up to approximately 4 years 3 months
DOR was defined as time from first response (PR or better) to timing of disease progression or death (due to any cause), whichever came first.
Up to approximately 4 years 3 months
Dose Escalation, Expansion Part A and Expansion Part B: Time-to-response (TTR)
Tidsramme: Up to approximately 4 years 3 months
TTR was defined as the time from date of first dose, or date of randomization for participants in the Expansion Part B, to time of first response (PR or better).
Up to approximately 4 years 3 months
Dose Escalation, Expansion Part A and Expansion Part B: Progression-free Survival (PFS)
Tidsramme: Up to approximately 4 years 3 months
PFS was defined as the time from the date of first dose, or date of randomization for participants in the Expansion Part B, to the date of progression or death (due to any cause), whichever came first.
Up to approximately 4 years 3 months
Dose Escalation, Expansion Part A and Expansion Part B: Overall Survival (OS)
Tidsramme: Up to approximately 4 years 3 months
OS was defined as the time from the date of first dose, or date of randomization for participants in the Expansion Part B, to the date of death due to any cause.
Up to approximately 4 years 3 months
Expansion Part A and Part B: Number of Participants With AEs and SAEs
Tidsramme: Up to approximately 4 years 3 months
An AE was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE was defined as an AE that met 1 of the following criteria: fatal or life-threatening, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, was medically significant (jeopardized the participant or may have required medical or surgical intervention to prevent one of the outcomes listed above), required inpatient hospitalization or prolongation of existing hospitalization. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Up to approximately 4 years 3 months
Expansion Part B: Percentage of Participants With Very Good Partial Response (VGPR) or Better
Tidsramme: Up to approximately 4 years 3 months
Based on Investigator Assessment per IMWG 2016 Criteria, VGPR was defined as serum and urine M-protein detectable by immunofixation (IFE) but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 h. Data are reported for the percentage of participants with a VGPR or better.
Up to approximately 4 years 3 months
Expansion Part B: Percentage of Participants With Complete Response (CR) or Better
Tidsramme: Up to approximately 4 years 3 months
CR was defined as negative IFE on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow aspirates based on Investigator assessment per IMWG response criteria. Data are reported for the percentage of participants with CR or better.
Up to approximately 4 years 3 months
Expansion Part B: Time to Next Therapy (TTNT)
Tidsramme: Up to approximately 4 years 3 months
TTNT for participants in the Expansion Part B was defined as the time from randomization to the start of subsequent anti-cancer therapy. Participants who withdrew consent or were lost to follow up or died due to causes other than disease progression were censored at their last disease assessment.
Up to approximately 4 years 3 months
Expansion Part B: Number of Participants With Anti-GEN3014 Antibodies and Anti-Daratumumab Antibodies
Tidsramme: Cycle 1 Day 22 up to a maximum of approximately 23.9 months (cycles = 28 days)
Venous blood samples were drawn for analysis of ADAs to GEN3014 and daratumumab. In the GEN3014 arm, participants were tested for anti-GEN3014-antibodies; in the daratumumab arm, participants were tested for anti-daratumumab-antibodies.
Cycle 1 Day 22 up to a maximum of approximately 23.9 months (cycles = 28 days)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Genmab

Efterforskere

  • Studieleder: Study Official, Genmab

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

9. marts 2021

Primær færdiggørelse (Faktiske)

30. juni 2025

Studieafslutning (Faktiske)

31. juli 2025

Datoer for studieregistrering

Først indsendt

9. marts 2021

Først indsendt, der opfyldte QC-kriterier

29. marts 2021

Først opslået (Faktiske)

1. april 2021

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

19. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

27. april 2026

Sidst verificeret

1. april 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • GCT3014-01
  • 2020-003781-40 (EudraCT nummer)
  • NL75422.056.21 (Registry Identifier: The Netherlands CCMO)
  • 2023-507086-26-00 (Ctis: EU CT Number)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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