Studio FiH per indagare la sicurezza, la farmacocinetica e l'efficacia del NaPi2b ADC TUB-040 in pazienti con NSCLC PROC o adenocarcinoma r/r (NAPISTAR1-01)
Un primo studio di fase I/IIa di incremento e ottimizzazione della dose nell'uomo per indagare la sicurezza, la tollerabilità, la farmacocinetica e l'efficacia di NaPi2b ADC TUB-040 in pazienti con cancro ovarico di alto grado (PROC) resistente al platino o r/r Adenocarcinoma Carcinoma polmonare non a piccole cellule (NSCLC)
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.
Panoramica dello studio
Stato
Intervento / Trattamento
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Contatto studio
- Nome: Gilead Clinical Study Information Center
- Numero di telefono: 1-833-445-3230 (GILEAD-0)
- Email: GileadClinicalTrials@gilead.com
Luoghi di studio
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Leuven, Belgio, 3000
- Reclutamento
- UZ Leuven - PPDS
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Berlin, Germania, 13353
- Reclutamento
- Charité- Universitaetsmedizin Berlin
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Cologne, Germania, 50937
- Reclutamento
- University Hospital of Cologne
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London, Regno Unito, SE1 9RT
- Attivo, non reclutante
- Guy's Hospital
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Cluj-Napoca, Romania, 40015
- Reclutamento
- ARENSIA Exploratory Medicine, LLC
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Madrid, Spagna, 28027
- Reclutamento
- Clínica Universidad de Navarra - Madrid
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Madrid, Spagna, 28223
- Reclutamento
- NEXT Madrid, University Hospital Quironsalud Madrid
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Alabama
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Birmingham, Alabama, Stati Uniti, 35294
- Reclutamento
- University of Alabama at Birmingham
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Georgia
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Atlanta, Georgia, Stati Uniti, 30322
- Reclutamento
- Winship Cancer Institute Emory University
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02215
- Reclutamento
- Dana Farber Cancer Institute (DFCI)
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New Jersey
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East Brunswick, New Jersey, Stati Uniti, 08816
- Reclutamento
- START New Jersey (Astera Cancer Center)
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New York
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New York, New York, Stati Uniti, 10011
- Reclutamento
- Mount Sinai
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Ohio
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Cincinnati, Ohio, Stati Uniti, 45219
- Reclutamento
- The Christ Hospital Physicians - Mt. Auburn
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Columbus, Ohio, Stati Uniti, 43210
- Reclutamento
- Ohio State University CRS
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Oklahoma
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Oklahoma City, Oklahoma, Stati Uniti, 73104
- Reclutamento
- Stephenson Cancer Center
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Oregon
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Medford, Oregon, Stati Uniti, 97504
- Reclutamento
- Asante Rogue Region al Medical Center
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Texas
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Fort Worth, Texas, Stati Uniti, 76104
- Reclutamento
- START Dallas Fort Worth
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Irving, Texas, Stati Uniti, 75039
- Reclutamento
- NEXT Oncology Dallas
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Utah
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West Valley City, Utah, Stati Uniti, 84119
- Reclutamento
- START Mountain Region
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Virginia
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Fairfax, Virginia, Stati Uniti, 22031
- Reclutamento
- NEXT Virginia
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Kyiv, Ucraina, 01135
- Attivo, non reclutante
- ARENSIA Exploratory Medicine, LLC
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Key Inclusion Criteria (for all phases)
- Male or non-pregnant, non-breastfeeding female, age 18 years or older at the date of consent.
- Disease not amenable to curative intent treatment.
- 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.
- Individuals with previous systemic topoisomerase I inhibitor treatment (e.g., Topotecan) are allowed in the study.
- Radiologically measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the INV.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
- Have a life expectancy of more than 12 weeks for disease-related mortality, as evaluated by the INV.
- Individuals must be willing to sign an archival tissue release form for research purposes and determination of biomarker expression.
- 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.
- Adequate organ function
- 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)).
- 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.
- 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.
- The individual must not have a history of non-compliance with medical regimens or be considered potentially unreliable and/or uncooperative.
- The individual must be willing to sign and date the informed consent form (ICF)
Key Exclusion Criteria (for all phases)
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The individual is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.
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History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.
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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.
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Individuals with spinal cord compression or active central nervous system disease, and/or carcinomatous meningitis.
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Prior radiotherapy <2 weeks from trial inclusion.
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Major surgery within 21 days prior to signing the ICF, unless the individual is recovered at that time.
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Has a history of non-infectious interstitial lung disease/pneumonitis (ILD)/pneumonitis/radiation pneumonitis that required steroids or has current ILD/pneumonitis.
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Has an oxygen saturation of <93% on room air at rest.
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Has a QTcF >470 ms
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History of nephrotic syndrome
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Active corneal disease, or history of corneal disease within 12 months prior to enrollment.
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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.
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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.
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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).
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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.
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Concurrent use of strong inhibitors or strong inducers of CYP3A4
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Live vaccines within 30 days prior to study entry.
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Individuals with acute or chronic infections such as:
- 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.
- Individuals with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
- HIV infected individuals must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease
- Any other known unresolved and active bacterial, viral, fungal, mycobacterial, or other infection at screening.
- History of severe and recurrent infections per INV judgment.
- History of progressive multifocal leukoencephalopathy
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione sequenziale
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: 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. |
Administered intravenous (IV) on day 1 of each 21-day treatment cycle |
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Sperimentale: 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. |
Administered intravenous (IV) on day 1 of each 21-day treatment cycle |
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Sperimentale: 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. |
Administered IV
Altri nomi:
Administered intravenous (IV) on day 1 of each 21-day treatment cycle |
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Sperimentale: 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. |
Administered intravenous (IV) on day 1 of each 21-day treatment cycle |
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Sperimentale: 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. |
Administered intravenous (IV) on day 1 of each 21-day treatment cycle |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Phase 1 and 2a: Percentage of Participants Experiencing Treatment-Emergent Adverse Event (TEAEs)
Lasso di tempo: First dose date up to 30 days post last dose (Up to 3 years)
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First dose date up to 30 days post last dose (Up to 3 years)
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Phase 1: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs)
Lasso di tempo: First dose up to 21 days
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First dose up to 21 days
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Phase 2a & 2b: Overall Response Rate (ORR) by Blinded Independent Central Review (BICR)
Lasso di tempo: Up to 3 years
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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
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Phase 1: Percentage of Participants Experiencing Serious Adverse Events (SAEs)
Lasso di tempo: First dose date up to 30 days post last dose (Up to 3 years)
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First dose date up to 30 days post last dose (Up to 3 years)
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Phase 1, 2a & 2b: Percentage of Participants Developing anti-TUB-040 antibodies and semiquantitative titer assessments
Lasso di tempo: From enrollment until 30 days after last study drug
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From enrollment until 30 days after last study drug
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Phase 2a & 2b: Percentage of Participants Experiencing TEAEs
Lasso di tempo: First dose date up to 30 days post last dose date (Up to 3 years)
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First dose date up to 30 days post last dose date (Up to 3 years)
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Phase 2a & 2b: Duration of Response (DOR) by BICR
Lasso di tempo: Up to 3 years
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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
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Phase 1, 2a & 2b: ORR by INV
Lasso di tempo: Up to 3 years
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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
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Phase 1, 2a & 2b: DOR by INV
Lasso di tempo: Up to 3 years
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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
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Phase 1, 2a & 2b: Progression-Free Survival (PFS) by INV
Lasso di tempo: Up to 3 years
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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
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Phase 1, 2a & 2b: Disease Control Rate (DCR) by INV
Lasso di tempo: Up to 3 years
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DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease, as assessed by INV. |
Up to 3 years
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Phase 2a & 2b: Progression-Free Survival (PFS) by BICR
Lasso di tempo: Up to 3 years
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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
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Phase 2a & 2b: Disease Control Rate (DCR) by BICR
Lasso di tempo: Up to 3 years
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DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease, as assessed by BICR. |
Up to 3 years
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Phase 1, 2a & 2b: Percentage of Participants Experiencing Grade ≥3 Lab Abnormalities
Lasso di tempo: Up to 3 years
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Up to 3 years
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Phase 1 & 2a: Pharmacokinetic (PK) Parameter of TUB-040, total Monoclonal Antibody (mAb), and Free Exatecan: Cmax
Lasso di tempo: Up to 3 years
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Cmax is defined as the maximum observed drug concentration. |
Up to 3 years
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Phase 1 & 2a: PK Parameter of TUB-040, Total mAb, and Free Exatecan: Cmin
Lasso di tempo: Up to 3 years
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The concentration of TUB-040 (conjugated ADC), total mAb, and free payload (Cmin will be derived). |
Up to 3 years
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Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Tmax
Lasso di tempo: Up to 3 years
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Tmax is defined as the time (observed time point) of Cmax. |
Up to 3 years
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Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Area Under Curve (AUC)
Lasso di tempo: Up to 3 years
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AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. |
Up to 3 years
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Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Half life (t1/2)
Lasso di tempo: Up to 3 years
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t1/2 is defined as the terminal elimination half-life at steady state. |
Up to 3 years
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Phase 2a & 2b: Overall Survival (OS)
Lasso di tempo: Up to 3 years
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OS is defined as the length of time from first dose until the date of death from any cause. |
Up to 3 years
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Phase 2a & 2b: Cancer Antigen (CA)-125 response according to Gynecological Cancer InterGroup (GCIG)
Lasso di tempo: Up to 3 years
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Up to 3 years
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Collaboratori e investigatori
Sponsor
Investigatori
- Direttore dello studio: Gilead Study Director, Gilead Sciences
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Malattie urogenitali
- Malattie genitali
- Malattie del sistema endocrino
- Neoplasie urogenitali
- Neoplasie per sede
- Neoplasie
- Malattie urogenitali femminili
- Malattie urogenitali femminili e complicanze della gravidanza
- Malattie delle vie respiratorie
- Malattie genitali, femmina
- Malattie polmonari
- Neoplasie delle ghiandole endocrine
- Neoplasie delle vie respiratorie
- Neoplasie toraciche
- Neoplasie polmonari
- Malattie ovariche
- Malattie annessiali
- Neoplasie genitali, femmina
- Disturbi gonadici
- Carcinoma, broncogeno
- Neoplasie bronchiali
- Neoplasie ovariche
- Carcinoma, polmone non a piccole cellule
- Aminoacidi, peptidi e proteine
- Proteine
- Anticorpi, monoclonali, umanizzati
- Anticorpi, monoclonali
- Anticorpi
- Immunoglobuline
- Immunoproteine
- Proteine del sangue
- Globuline sieriche
- Globuline
- Bevacizumab
Altri numeri di identificazione dello studio
- NAPISTAR 1-01
- 2024-511074-80 (Numero EudraCT)
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Informazioni su farmaci e dispositivi, documenti di studio
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