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Intratekal kombination av PD-1/CTLA-4 bispecifik antikropp och pemetrexed för Leptomeningeal metastasering.

10 november 2026 uppdaterad av: Zhenyu Pan, Guangzhou Medical University

En klinisk fas I/II studie av en intratekal kombination av PD-1/CTLA-4 bispecifik antikropp och pemetrexed för Leptomeningeal metastasering från fasta tumörer.

Leptomeningeal metastasis, characterized by tumor cells infiltrating and proliferating in the subarachnoid space, represents a distinct pattern of central nervous system involvement and is a fatal complication of malignant tumors. This phase I/II study is to evaluate the recommended dose, safety, feasibility, and therapeutic response of intrathecal Programmed Death-1 (PD-1)/Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) bispecific antibodies combined with pemetrexed in patients with leptomeningeal metastasis.

Studieöversikt

Status

Rekrytering

Betingelser

Intervention / Behandling

Detaljerad beskrivning

Leptomeningeal metastasis is a severe complication of advanced cancer, traditionally managed with intrathecal chemotherapy. Recently, immunotherapy has emerged as a promising treatment for solid tumors. The preliminary results from our previous study on PD-1 combined with pemetrexed intrathecal administration showed safety and feasibility for leptomeningeal metastasis from solid tumors with potential activity. Currently, a clinical trial in Switzerland is evaluating the efficacy of dual immunotherapy (PD-1 plus CTLA-4 inhibitors) administered intrathecally for leptomeningeal metastasis. Cadonilimab, the world's first PD-1/CTLA-4 bispecific antibody, has shown favorable safety and efficacy in clinical practice, further supporting its potential in this setting. The primary objectives are to determine the recommended dose of intrathecal cadonilimab in combination with pemetrexed and to assess safety based on the incidence of treatment-related adverse events. Clinical response rate, disease control rate, and overall survival are also evaluated. Patients undergo cerebrospinal fluid and blood specimen collection to evaluate potential clinical, molecular, and/or immune predictors of treatment efficacy and safety.

Studietyp

Interventionell

Inskrivning (Beräknad)

39

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

Studera Kontakt Backup

  • Namn: Zhenyu Pan, PhD, MD
  • Telefonnummer: +8617702171708
  • E-post: dr-zypan@163.com

Studieorter

  • Kina
      • Beijing, Kina, 101100
        • Rekrytering
        • Beijing Chest Hospital, Capital Medical University
        • Kontakt:
        • Huvudutredare:
          • Zhenyu Pan
      • Shanghai, Kina
        • Aktiv, inte rekryterande
        • Jinshan Hospital, Fudan University
    • Guangdong
      • Huizhou, Guangdong, Kina, 516000
        • Rekrytering
        • The Affiliated Huizhou Hospital, Guangzhou Medical University
        • Kontakt:
        • Kontakt:

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

21 år till 75 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of solid tumors; Cerebrospinal fluid cytopathology is positive.
  2. Male or female aged between 21 and 75 years; Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3.
  3. No history of severe nervous system disease; No severe dyscrasia.

Exclusion Criteria:

  1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.
  2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment.
  3. A history of HIV or AIDS, acute or chronic hepatitis B or C infection, previous anti-PD1 therapy-induced pneumonitis, or have ongoing >Grade 2 adverse events of such therapy; or ongoing autoimmune disease that required systemic treatment in the past 2 years.
  4. The first month to treatment, as well as during induction and consolidation therapy, new drugs effective against leptomeningeal metastases were used, excluding those previously administered. These primarily included small molecule targeted therapies, such as EGFR-TKI/ALK-TKI drugs like Osimertinib and Lorlatinib.
  5. Patients with poor compliance or other reasons that were unsuitable for this study.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: PD-1/CTLA-4 Bispecific Antibody with Pemetrexed

This study is a prospective, single-arm, Phase I/II clinical trial. The primary objective is to determine the recommended Phase II dose (RP2D) for the intrathecal combination of PD-1/CTLA-4 bispecific antibody with pemetrexed and and safety based on the incidence of treatment-related adverse events. Clinical response rate (CRR), disease control rate (DCR) and overall survival (OS) are also evaluated. Patients will have cerebrospinal fluid (CSF) and blood specimen collection for the evaluation of predictors (clinical, molecular, and/or immune) of the efficacy and safety of this regimen.
Läkemedel: Cadonilimab (AK104)

Intrathecal injection of PD-1/CTLA-4 bispecific antibody was administered every two weeks for six weeks during the induction phase, followed by monthly injections during the maintenance phase, until recurrence or death.

Läkemedel: Pemetrexed (Alimta)

Pemetrexed was administrated by intrathecal injection, first as induction therapy, twice per week for 2 weeks, followed by consolidation therapy, once per week for 4 weeks, then maintenance therapy, once per month until the patient's death, leptomeningeal metastasis progresses, or intolerable severe adverse events occurred.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Recommended Phase II Dose (RP2D)
Tidsram: Dose limiting toxicity was assessed during the first 6 weeks after the first intrathecal administration.

The recommended phase II dose. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g., meningitis) or other grade 4 toxicity.
Dose limiting toxicity was assessed during the first 6 weeks after the first intrathecal administration.
Incidence of treatment-related adverse events
Tidsram: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months

The incidence of treatment-related adverse events were measured for determining tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). Events of grade 3-5 are defined as moderate and severe adverse events
From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months

Andra resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Clinical response rate
Tidsram: Time Frame: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months

The response assessment in neuro-oncology criteria (RANO) proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.
Time Frame: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Disease control rate (DCR)
Tidsram: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.

Disease control rate was defined as proportion of patients achieving clinical response or stable disease. Clinical response and stable disease were determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.
From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
Overall survival(OS)
Tidsram: From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 6 months)

Overall survival was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.
From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 6 months)

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Guangzhou Medical University

Samarbetspartners

Jinshan Hospital Fudan University

Utredare

  • Huvudutredare: Zhenyu Pan, PhD, MD, Jinshan Hospital Fudan University

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

7 mars 2025

Primärt slutförande (Beräknad)

30 december 2027

Avslutad studie (Beräknad)

30 september 2028

Studieregistreringsdatum

Först inskickad

1 januari 2025

Först inskickad som uppfyllde QC-kriterierna

1 januari 2025

Första postat (Faktisk)

7 januari 2025

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

12 november 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

10 november 2026

Senast verifierad

1 juli 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • IMPACT

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