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Étude FiH pour étudier l'innocuité, la pharmacocinétique et l'efficacité du NaPi2b ADC TUB-040 chez les patients atteints de PROC ou d'adénocarcinome r/r CPNPC (NAPISTAR1-01)

30 octobre 2026 mis à jour par: Gilead Sciences

Une première étude de phase I/IIa d'augmentation et d'optimisation de dose chez l'homme pour étudier l'innocuité, la tolérance, la pharmacocinétique et l'efficacité du NaPi2b ADC TUB-040 chez des patientes atteintes d'un cancer de l'ovaire de haut grade (PROC) ou r/r résistant au platine Adénocarcinome Cancer du poumon non à petites cellules (CPNPC)

The goal of this clinical study is to learn more about the study drug, TUB-040, including its safety, tolerability, pharmacokinetics, and preliminary efficacy, and to determine the best dose of TUB-040 in participants with ovarian cancer or non-small cell lung cancer (NSCLC).

The primary objectives of this study are:

Phase 1: To determine the safety and tolerability of TUB-040 and determine the maximum tolerated dose (MTD) or the identified dose for optimization (IDO).

Phase 2a: To assess safety of TUB-040, the preliminary efficacy of TUB-040, and to identify the recommended phase II dose (RP2D) for further development of TUB-040 .

Phase 2b: To determine the efficacy of TUB-040 in patients with PROC.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

334

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • Allemagne
      • Berlin, Allemagne, 13353
        • Recrutement
        • Charité- Universitaetsmedizin Berlin
      • Cologne, Allemagne, 50937
        • Recrutement
        • University Hospital of Cologne
  • Belgique
      • Leuven, Belgique, 3000
        • Recrutement
        • UZ Leuven - PPDS
  • Espagne
      • Madrid, Espagne, 28027
        • Recrutement
        • Clínica Universidad de Navarra - Madrid
      • Madrid, Espagne, 28223
        • Recrutement
        • NEXT Madrid, University Hospital Quironsalud Madrid
  • Roumanie
      • Cluj-Napoca, Roumanie, 40015
        • Recrutement
        • ARENSIA Exploratory Medicine, LLC
  • Royaume-Uni
      • London, Royaume-Uni, SE1 9RT
        • Actif, ne recrute pas
        • Guy's Hospital
  • Ukraine
      • Kyiv, Ukraine, 01135
        • Actif, ne recrute pas
        • ARENSIA Exploratory Medicine, LLC
  • États-Unis
    • Alabama
      • Birmingham, Alabama, États-Unis, 35294
        • Recrutement
        • University of Alabama at Birmingham
    • Georgia
      • Atlanta, Georgia, États-Unis, 30322
        • Recrutement
        • Winship Cancer Institute Emory University
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02215
        • Recrutement
        • Dana Farber Cancer Institute (DFCI)
    • New Jersey
      • East Brunswick, New Jersey, États-Unis, 08816
        • Recrutement
        • START New Jersey (Astera Cancer Center)
    • New York
      • New York, New York, États-Unis, 10011
        • Recrutement
        • Mount Sinai
    • Ohio
      • Cincinnati, Ohio, États-Unis, 45219
        • Recrutement
        • The Christ Hospital Physicians - Mt. Auburn
      • Columbus, Ohio, États-Unis, 43210
        • Recrutement
        • Ohio State University CRS
    • Oklahoma
      • Oklahoma City, Oklahoma, États-Unis, 73104
        • Recrutement
        • Stephenson Cancer Center
    • Oregon
      • Medford, Oregon, États-Unis, 97504
        • Recrutement
        • Asante Rogue Region al Medical Center
    • Texas
      • Fort Worth, Texas, États-Unis, 76104
        • Recrutement
        • START Dallas Fort Worth
      • Irving, Texas, États-Unis, 75039
        • Recrutement
        • NEXT Oncology Dallas
    • Utah
      • West Valley City, Utah, États-Unis, 84119
        • Recrutement
        • START Mountain Region
    • Virginia
      • Fairfax, Virginia, États-Unis, 22031
        • Recrutement
        • NEXT Virginia

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Key Inclusion Criteria (for all phases)

  1. Male or non-pregnant, non-breastfeeding female, age 18 years or older at the date of consent.
  2. Disease not amenable to curative intent treatment.
  3. Individuals have exhausted the standard of care treatment (SoC) with expected survival benefit and are not denied SoC with expected survival benefit by participating in the trial.
  4. Individuals with previous systemic topoisomerase I inhibitor treatment (e.g., Topotecan) are allowed in the study.
  5. Radiologically measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the INV.
  6. Eastern Cooperative Oncology Group (ECOG) 0-1.
  7. Have a life expectancy of more than 12 weeks for disease-related mortality, as evaluated by the INV.
  8. Individuals must be willing to sign an archival tissue release form for research purposes and determination of biomarker expression.
  9. Individuals must be willing to undergo a non-contrast high resolution computed tomography (HRCT) of the thorax scan and pulmonary function testing (PFT) at screening.
  10. Adequate organ function
  11. Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤grade 1 (except alopecia, hyperpigmentation, or discoloration (incl. vitiligo) of the skin and nails, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic grade 2 peripheral sensory neuropathy after prior taxane therapy or anticancer treatment such as but not limited to immune oncology therapy (IOs)).
  12. Individuals of childbearing potential (FCBP) who are sexually active with a non-sterilized partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions until the end of exposure, plus 5 half-lives and 6 months add-on in the case of individuals assigned female at birth.
  13. In the opinion of the investigator, the individual must be able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations.
  14. The individual must not have a history of non-compliance with medical regimens or be considered potentially unreliable and/or uncooperative.
  15. The individual must be willing to sign and date the informed consent form (ICF)

Key Exclusion Criteria (for all phases)

  1. The individual is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.

  2. History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.

  3. Individuals are not allowed to participate in interventional clinical studies either concurrently or within the previous 28 days or within 5 half-lives of any investigational pharmacologic agents or imaging materials, including dyes, investigational surgical techniques, or devices.

  4. Individuals with spinal cord compression or active central nervous system disease, and/or carcinomatous meningitis.

  5. Prior radiotherapy <2 weeks from trial inclusion.

  6. Major surgery within 21 days prior to signing the ICF, unless the individual is recovered at that time.

  7. Has a history of non-infectious interstitial lung disease/pneumonitis (ILD)/pneumonitis/radiation pneumonitis that required steroids or has current ILD/pneumonitis.

  8. Has an oxygen saturation of <93% on room air at rest.

  9. Has a QTcF >470 ms

  10. History of nephrotic syndrome

  11. Active corneal disease, or history of corneal disease within 12 months prior to enrollment.

  12. Active, uncontrolled or severe impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic, or hematopoietic systems which, in the opinion of the investigator, would predispose the individual to the development of complications from the administration of protocol therapy.

  13. History of another malignancy with ongoing treatment or not yet free from disease for 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.

  14. Documented other concurrent non-malignant comorbidities such as unstable or uncontrolled pectoral angina, myocardial infarction during the last 6 months, valvular heart disease that requires treatment, acute myocarditis, or congestive heart failure (CHF) (New York Heart Association III or IV).

  15. Any anti-tumor chemotherapy, systemic anti-cancer therapy, radiotherapy (except for local radiation therapy of lesions that may cause imminent complications), hormonal therapy, immunotherapy, or corticoid therapy.

  16. Concurrent use of strong inhibitors or strong inducers of CYP3A4

  17. Live vaccines within 30 days prior to study entry.

  18. Individuals with acute or chronic infections such as:

    1. Individuals who are HBsAg positive are eligible if they have received Hepatitis B virus (HBV) anti-viral therapy for at least 4 weeks and have an undetectable HBV viral load prior to randomization.
    2. Individuals with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
    3. HIV infected individuals must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease
    4. Any other known unresolved and active bacterial, viral, fungal, mycobacterial, or other infection at screening.
    5. History of severe and recurrent infections per INV judgment.
    6. History of progressive multifocal leukoencephalopathy

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation séquentielle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Phase 1: Cohort 1: Dose Escalation in Platinum Resistant Ovarian Cancer (PROC)

Participants will receive escalating doses of TUB-040 every 3 weeks until the disease progresses or the patient has to stop due to side effects.
Médicament: TUB-040

Administered intravenous (IV) on day 1 of each 21-day treatment cycle
Expérimental: Phase 1: Cohort 2: Dose Escalation in R/R NSCLC of the adenocarcinoma subtype

Participants will receive escalating doses of TUB-040 every 3 weeks until the disease progresses or the patient has to stop due to side effects.
Médicament: TUB-040

Administered intravenous (IV) on day 1 of each 21-day treatment cycle
Expérimental: Phase 1: Cohort 3: PROC, Combination with Bevacizumab (BEV)

Participants will receive escalating doses of TUB-040 combined with BEV every 3 weeks until the disease progresses or the patient has to stop due to side effects.
Médicament: Bevacizumab

Administered IV

Autres noms:
  • VEB
Médicament: TUB-040

Administered intravenous (IV) on day 1 of each 21-day treatment cycle
Expérimental: Phase 2a: Dose Optimization in PROC

Participants will receive two different dose levels of TUB-040 every 3 weeks until the disease progresses or the patient has to stop due to side effects.
Médicament: TUB-040

Administered intravenous (IV) on day 1 of each 21-day treatment cycle
Expérimental: Phase 2b: Dose Expansion in PROC

Patients will receive TUB-040 at the safe dose established during dose escalation until disease progression or unacceptable toxicity.
Médicament: TUB-040

Administered intravenous (IV) on day 1 of each 21-day treatment cycle

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Phase 1 and 2a: Percentage of Participants Experiencing Treatment-Emergent Adverse Event (TEAEs)
Délai: First dose date up to 30 days post last dose (Up to 3 years)
First dose date up to 30 days post last dose (Up to 3 years)
Phase 1: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs)
Délai: First dose up to 21 days
First dose up to 21 days
Phase 2a & 2b: Overall Response Rate (ORR) by Blinded Independent Central Review (BICR)
Délai: Up to 3 years

ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR), as assessed by BICR.
Up to 3 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Phase 1: Percentage of Participants Experiencing Serious Adverse Events (SAEs)
Délai: First dose date up to 30 days post last dose (Up to 3 years)
First dose date up to 30 days post last dose (Up to 3 years)
Phase 1, 2a & 2b: Percentage of Participants Developing anti-TUB-040 antibodies and semiquantitative titer assessments
Délai: From enrollment until 30 days after last study drug
From enrollment until 30 days after last study drug
Phase 2a & 2b: Percentage of Participants Experiencing TEAEs
Délai: First dose date up to 30 days post last dose date (Up to 3 years)
First dose date up to 30 days post last dose date (Up to 3 years)
Phase 2a & 2b: Duration of Response (DOR) by BICR
Délai: Up to 3 years

DOR is defined as the interval from the first documentation of CR or PR until the date of first documented disease progression or death, whichever comes first, as assessed by BICR.
Up to 3 years
Phase 1, 2a & 2b: ORR by INV
Délai: Up to 3 years

ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR), as assessed by Investigator (INV).
Up to 3 years
Phase 1, 2a & 2b: DOR by INV
Délai: Up to 3 years

DOR is defined as the interval from the first documentation of CR or PR until the date of first documented disease progression or death, whichever comes first, as assessed by INV.
Up to 3 years
Phase 1, 2a & 2b: Progression-Free Survival (PFS) by INV
Délai: Up to 3 years

PFS is defined as the time from first dose date until disease progression or death from any cause, whichever comes first, as assessed by INV.
Up to 3 years
Phase 1, 2a & 2b: Disease Control Rate (DCR) by INV
Délai: Up to 3 years

DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease, as assessed by INV.
Up to 3 years
Phase 2a & 2b: Progression-Free Survival (PFS) by BICR
Délai: Up to 3 years

PFS is defined as the time from first dose date until disease progression or death from any cause, whichever comes first, as assessed by BICR.
Up to 3 years
Phase 2a & 2b: Disease Control Rate (DCR) by BICR
Délai: Up to 3 years

DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease, as assessed by BICR.
Up to 3 years
Phase 1, 2a & 2b: Percentage of Participants Experiencing Grade ≥3 Lab Abnormalities
Délai: Up to 3 years
Up to 3 years
Phase 1 & 2a: Pharmacokinetic (PK) Parameter of TUB-040, total Monoclonal Antibody (mAb), and Free Exatecan: Cmax
Délai: Up to 3 years

Cmax is defined as the maximum observed drug concentration.
Up to 3 years
Phase 1 & 2a: PK Parameter of TUB-040, Total mAb, and Free Exatecan: Cmin
Délai: Up to 3 years

The concentration of TUB-040 (conjugated ADC), total mAb, and free payload (Cmin will be derived).
Up to 3 years
Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Tmax
Délai: Up to 3 years

Tmax is defined as the time (observed time point) of Cmax.
Up to 3 years
Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Area Under Curve (AUC)
Délai: Up to 3 years

AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Up to 3 years
Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Half life (t1/2)
Délai: Up to 3 years

t1/2 is defined as the terminal elimination half-life at steady state.
Up to 3 years
Phase 2a & 2b: Overall Survival (OS)
Délai: Up to 3 years

OS is defined as the length of time from first dose until the date of death from any cause.
Up to 3 years
Phase 2a & 2b: Cancer Antigen (CA)-125 response according to Gynecological Cancer InterGroup (GCIG)
Délai: Up to 3 years
Up to 3 years

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Gilead Sciences

Les enquêteurs

  • Directeur d'études: Gilead Study Director, Gilead Sciences

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

12 juin 2024

Achèvement primaire (Estimé)

1 décembre 2027

Achèvement de l'étude (Estimé)

1 décembre 2027

Dates d'inscription aux études

Première soumission

6 février 2024

Première soumission répondant aux critères de contrôle qualité

6 mars 2024

Première publication (Réel)

12 mars 2024

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

3 novembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

30 octobre 2026

Dernière vérification

1 octobre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • NAPISTAR 1-01
  • 2024-511074-80 (Numéro EudraCT)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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