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A Clinical Study Evaluating a New Treatment Strategy for Patients With Advanced Pancreatic Cancer Who Have Not Received Prior Treatment for Advanced Disease. (NUMANTIA-2)

11 maggio 2026 aggiornato da: Nelum Corp

A Randomized Phase II Study of Priming Treatment With the Hedgehog Inhibitor NLM-001 Prior to Gemcitabine/Nab-Paclitaxel (GNab-P) plusBotensilimab and Balstilimab (Bot/Bal) Versus GNab-P in Patients With Previously Untreated Advanced Pancreatic Cancer (NUMANTIA-2)

Phase II, open label, randomized multicenter study to evaluate efficacy and safety of study treatment in previously untreated patients with advanced pancreatic cancer. Patients will receive study treatment for a maximum of 24 months or until progression disease or until unacceptable toxicity. In the experimental arm, patients who discontinue chemotherapy for reasons other than disease progression may continue receiving the remaining study drugs (NLM-001, botensilimab and balstilimab) up to a maximum of 24 months, according to schedule.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Participants will be centrally randomized 1:1 to one of the study arms. Randomization will be stratified according to:

  1. ECOG Performance Status (0 vs 1)
  2. Presence of liver metastases (yes vs no)

Tipo di studio

Interventistico

Iscrizione (Stimato)

40

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Spagna
    • Aragon
      • Zaragoza, Aragon, Spagna
        • Hospital Universitario Miguel Servet
        • Contatto:
          • Roberto Pazo, MD
        • Investigatore principale:
          • Roberto Pozo, MD
    • Barcelona
      • Barcelona, Barcelona, Spagna
        • Hospital Clinic Barcelona
        • Investigatore principale:
          • Teresa Macarulla, MD
        • Contatto:
          • Teresa Macarulla, MD
    • Cantabria
      • Santander, Cantabria, Spagna
        • Hospital Universitario Marqués de Valdecilla
        • Investigatore principale:
          • Fernando Rivera, MD
        • Contatto:
          • Fernando Rivera, MD
    • Gipuzkoa
      • San Sebastián, Gipuzkoa, Spagna
        • Hospital Universitario DE Donostia
        • Contatto:
          • Aitziber Gil-Negrete, MD
        • Investigatore principale:
          • Aitziber Gil-Negrete, MD
    • La Coruña
      • Santiago de Compostela, La Coruña, Spagna
        • Complexo Hospitalario Universitario De Santiago
        • Contatto:
          • Elena María Brozos, MD
        • Investigatore principale:
          • Elena María Brozos, MD
    • Málaga
      • Málaga, Málaga, Spagna
        • Hospital Universitario Virgen de la Victoria
        • Contatto:
          • Laura Medina, MD
        • Investigatore principale:
          • Laura Medina, MD

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  1. Investigators must ensure that patients are able to understand the requirements of the study and provide informed consent.
  2. Age ≥18 years.
  3. Histological or cytological diagnosis of pancreatic adenocarcinoma.
  4. Stage IV disease.
  5. No prior treatment for advanced disease. Patients who have received chemotherapy for localized disease are eligible if they progress within six months from the last chemotherapy treatment.
  6. Measurable disease per iRECIST 1.1 as determined by the investigator.
  7. ECOG (Eastern Cooperative Oncology Group) PS 0-1.

  8. Sufficient hematopoietic, renal and liver function as defined as:

    • Neutrophil count ≥ 1.5 x 10^9 / L
    • Platelet count ≥ 100 x 10^9 / L
    • Bilirubin ≤ 1.5 x ULN (upper limit of normal)
    • AST and / or ALT ≤2.5 x ULN or ≤5 for patients with liver disease
    • Serum creatinine ≤ 1.5 x ULN
  9. Tumor lesion amenable to safe repeated tumor biopsy.
  10. Women of child-bearing age and men who wish to participate in the study must agree to use appropriate contraceptive methods from the signing of informed consent until 6 months for women and 3 months for men after discontinuation of the study drug o Adequate contraception includes abstinence, oral contraceptives, transdermal patches, and injections that prolong release of a progestogen (starting at least 4 weeks prior to the administration of the investigational drug), condom or female condom (diaphragm or condom / vaginal) plus spermicide, intrauterine device (IUD), implant or a vaginal ring (placed at least 4 weeks prior to administration of investigational drug) or male partner sterilization (vasectomy with documentation of azoospermia) before the inclusion of the woman in the trial if the male is the only sex partner of the woman (see appendix G).

Exclusion Criteria:

  1. Active or uncontrolled infectious disease or serious medical condition that may interfere with the patient's eligibility or treatment.
  2. History of psychiatric condition that would compromise the patient's ability to understand or comply with the requirements of the protocol, or the ability to provide informed consent.
  3. Concurrent antineoplastic therapy.
  4. Prior chemotherapy or chemo-radiation therapy for advanced pancreatic cancer.
  5. Prior anti-PD-(L)1 or anti-CTLA-4 as prior therapy(ies).
  6. Pregnant or lactating women.
  7. History of allergic reactions attributed to compounds of similar chemical structure or similar biological study drug composition.
  8. History of life-threatening serious adverse events to Gemcitabine or Nab-Paclitaxel.
  9. Patients requiring or being treated with potent CYP3A4 inhibitors and inducers.
  10. Other active malignancies undergoing or requiring systemic treatment.
  11. History of interstitial lung disease.
  12. Subjects with history or presence of a known clotting disorder or difficulty achieving haemostasis will be excluded.

  13. Primary or secondary immunodeficiency, including immunosuppressive disease or autoimmune disease (including autoimmune endocrinopathies).

    Note: Subjects with type 1 diabetes, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible. Subjects with Type 2 diabetes mellitus are allowed.

  14. Subjects with a known history of human immunodeficiency virus 1 and 2, human T lymphotropic virus 1.

  15. Prior treatment with anticancer therapies, immunosuppressive agents, corticosteroids, radiation, investigational drugs or vaccines within the following time intervals before the first dose of study treatment (C1D1):

    (i) Cytotoxic chemotherapy: within 3 weeks prior to C1D1. (ii) Monoclonal antibodies, antibody-drug conjugates or radioimmunoconjugates: within 4 weeks or 5 half-lives, whichever is shorter.

    (iii) Small-molecule targeted therapies, including tyrosine kinase inhibitors: within 2 weeks or 5 half-lives, whichever is shorter.

    (iv) Any other anti-neoplastic therapy (including experimental agents): within 3 weeks, except:

    • Investigational drugs or devices must not have been administered within 21 days or 5 half-lives (whichever is longer).

    • For investigational agents with long half-lives (>5 days), earlier enrolment requires approval by the medical monitor.

      (v) Radiotherapy: - A 1-week washout is permitted for palliative radiation to non-CNS lesions, with medical monitor approval.

    • Patients must not have experienced radiation pneumonitis or be receiving chronic corticosteroids for this condition.

    (vi) Corticosteroids: - No systemic corticosteroids within 7 days, except:

    • inhaled or topical corticosteroids,
    • corticosteroid premedication for contrast allergy,
    • physiologic replacement doses, with medical monitor approval. (vii) Immunosuppressive therapies: - No immunosuppressive treatment within 7 days, except for the permitted corticosteroid uses listed above.

    (viii) SARS-CoV-2 vaccination:

    • No COVID-19 vaccine within 7 days before randomization.
    • When feasible, multi-dose vaccine series should be completed prior to randomization.

  16. Has not recovered to grade ≤1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting therapy.

    Note: Subjects with grade ≤2 neuropathy and alopecia are an exception and may enroll.

  17. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful.

  18. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of study enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication.

    a. QTcF (QT interval corrected using Fridericia's formula) of > 480 ms.

  19. Concurrent participation in other investigational drug trials.

  20. Known central nervous system (CNS) involvement as follows:

    • Untreated CNS metastases.
    • Leptomeningeal metastases. Note: Patients may be eligible if CNS metastases have been treated and patients have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment).
  21. Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection. Participants who are receiving or who have received anti-HBV therapy and have undetectable HBV DNA for at least 6 months prior to study enrollment are eligible. Serological testing for HBV at screening is not required.
  22. Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Participants on or who have received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study enrollment. Serological testing for HCV at screening is not required.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: Control Arm
Gemcitabine (G): 1,000 mg/m2 Nab-Paclitaxel (Nab-P): 125 mg/m2
Droga: Gemcitabine (1000 mg/m2)
Gemcitabine 1,000 mg / m2 IV administered on days 1, 8 and 15 in cycles of 28 days.
Droga: Nab-paclitaxel (Abraxane)
Nab-P 125 mg / m2 IV administered on days 1, 8 and 15 in cycles of 28 days.
Sperimentale: Experimental Arm
NLM-001: 800 mg/day Gemcitabine (G): 1,000 mg/m2 Nab-Paclitaxel (Nab-P): 125 mg/m2 Botensilimab (Bot, CTLA-4 inhibitor): 75 mg Balstilimab (Bal, PD-1 inhibitor): 240 mg
Droga: Gemcitabine (1000 mg/m2)
Gemcitabine 1,000 mg / m2 IV administered on days 1, 8 and 15 in cycles of 28 days.
Droga: Nab-paclitaxel (Abraxane)
Nab-P 125 mg / m2 IV administered on days 1, 8 and 15 in cycles of 28 days.
Droga: NLM-001
NLM-001: 800 mg/day, p.o, once daily (4 tablets of 200 mg) days -4 to -1 and 10-13 of each cycle.
Droga: Botensilimab
Botensilimab: 75 mg every 6 weeks for 4 administrations, from D1C1.
Droga: Balstililmab
Balstilimab: 240 mg IV Day 1 and Day 15 of each 28-day cycle.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
To evaluate the response rate in each of the study arms, assessed according to iRECIST criteria, including the confirmation of progression to distinguish true progression from potential pseudoprogression.
Lasso di tempo: 12 months
Objective Response Rate (ORR): Complete Response (CR) + Partial Response (PR), according to iRECIST 1.1 criteria, according to investigator criteria. Suspected progression (including possible pseudoprogression due to immune-related effects or new lesions) must be confirmed with repeat imaging performed 4-8 weeks after the initial assessment before considering the patient as having true disease progression.
12 months

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
To evaluate safety profile and tolerability of study treatment according to NCI-CTCAE v 5.0 criteria.
Lasso di tempo: 12 months
Safety profile will be assessed according to NCI-CTCAE v 5.0 criteria. The number of patients experiencing each AE will be summarized by CTCAE grade.
12 months
To evaluate treatment efficacy according to progression free survival (PFS)
Lasso di tempo: 12 months
Progression Free Survival (PFS): PFS is defined as the time in months from the patient's randomization until patient progression according to iRECIST 1.1 criteria or death.
12 months
To evaluate treatment efficacy according to 6 months PFS
Lasso di tempo: 6 months
Progression Free Survival (PFS): PFS is defined as the time in months from the patient's randomization until patient progression according to iRECIST 1.1 criteria or death.
6 months
To evaluate treatment efficacy according todisease control rate (DCR)
Lasso di tempo: 12 months
Disease Control Rate (DCR): Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) evaluated by iRECIST 1.1 criteria according to investigator criteria.
12 months
To evaluate treatment efficacy according to duration of response (DoR)
Lasso di tempo: 12 months
Duration of Response (DoR): DoR is defined as the time in months from the date of first documented objective response (complete response [CR] or partial response [PR], whichever is first) until the date of first documented disease progression or death from any cause, whichever occurs first.
12 months
To evaluate treatment efficacy according to duration of clinical benefit (DoCB)
Lasso di tempo: 12 months
Duration of Clinical Benefit (DoCB): DoCB is defined, for subjects achieving clinical benefit (complete response [CR], partial response [PR], or stable disease [SD] per iRECIST v1.1), as the time from the date of first documented evidence of clinical benefit (CR, PR, or SD) until the date of first documented radiographic disease progression or death from any cause, whichever occurs first.
12 months
To evaluate treatment efficacy according to overall survival.
Lasso di tempo: 12 months
Overall Survival (OS): OS is defined as the time in months from the patient's randomization until death.
12 months
To evaluate CA 19.9 levels during study treatment (Decrease > 50%)
Lasso di tempo: 12 months
Decrease in CA 19.9 levels > 50%. Responses based on levels of the tumor marker CA 19.9 will be calculated as the maximum percentage of change with respect to baseline in those patients with a baseline higher than 1.25 times the upper limit of normal in the local laboratory of each center.
12 months
To evaluate CA 19.9 levels during study treatment (Decrease > 75%)
Lasso di tempo: 12 months
Decrease in CA 19.9 levels > 75%. Responses based on levels of the tumor marker CA 19.9 will be calculated as the maximum percentage of change with respect to baseline in those patients with a baseline higher than 1.25 times the upper limit of normal in the local laboratory of each center.
12 months
To evaluate CA 19.9 levels during study treatment (Decrease > 90%).
Lasso di tempo: 12 months
Decrease in CA 19.9 levels > 90%. Responses based on levels of the tumor marker CA 19.9 will be calculated as the maximum percentage of change with respect to baseline in those patients with a baseline higher than 1.25 times the upper limit of normal in the local laboratory of each center.
12 months

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Nelum Corp

Collaboratori

Apices Soluciones S.L.
PH Research, S.L.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

15 luglio 2026

Completamento primario (Stimato)

28 febbraio 2029

Completamento dello studio (Stimato)

28 febbraio 2029

Date di iscrizione allo studio

Primo inviato

5 maggio 2026

Primo inviato che soddisfa i criteri di controllo qualità

5 maggio 2026

Primo Inserito (Effettivo)

11 maggio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

13 maggio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

11 maggio 2026

Ultimo verificato

1 maggio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • NLM-2026-02 / NUMANTIA-2
  • 2026-525796-90-00 (Ctis)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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