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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. května 2026 aktualizováno: 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.

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

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)

Typ studie

Intervenční

Zápis (Odhadovaný)

40

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dospělý
  • Starší dospělý

Přijímá zdravé dobrovolníky

Ne

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Aktivní komparátor: Control Arm
Gemcitabine (G): 1,000 mg/m2 Nab-Paclitaxel (Nab-P): 125 mg/m2
Lék: Gemcitabine (1000 mg/m2)
Gemcitabine 1,000 mg / m2 IV administered on days 1, 8 and 15 in cycles of 28 days.
Lék: Nab-paclitaxel (Abraxane)
Nab-P 125 mg / m2 IV administered on days 1, 8 and 15 in cycles of 28 days.
Experimentální: 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
Lék: Gemcitabine (1000 mg/m2)
Gemcitabine 1,000 mg / m2 IV administered on days 1, 8 and 15 in cycles of 28 days.
Lék: Nab-paclitaxel (Abraxane)
Nab-P 125 mg / m2 IV administered on days 1, 8 and 15 in cycles of 28 days.
Lék: 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.
Lék: Botensilimab
Botensilimab: 75 mg every 6 weeks for 4 administrations, from D1C1.
Lék: Balstililmab
Balstilimab: 240 mg IV Day 1 and Day 15 of each 28-day cycle.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
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.
Časové okno: 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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
To evaluate safety profile and tolerability of study treatment according to NCI-CTCAE v 5.0 criteria.
Časové okno: 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)
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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.
Časové okno: 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%)
Časové okno: 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%)
Časové okno: 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%).
Časové okno: 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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Nelum Corp

Spolupracovníci

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

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

15. července 2026

Primární dokončení (Odhadovaný)

28. února 2029

Dokončení studie (Odhadovaný)

28. února 2029

Termíny zápisu do studia

První předloženo

5. května 2026

První předloženo, které splnilo kritéria kontroly kvality

5. května 2026

První zveřejněno (Aktuální)

11. května 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

13. května 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

11. května 2026

Naposledy ověřeno

1. května 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

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

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

NE

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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