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Clinical Study of Novel Therapeutic Vaccine for Advanced Solid Tumors

4. maj 2026 opdateret af: Xingchen Peng, West China Hospital

Safety, Tolerability, and Preliminary Antitumor Activity of Novel Therapeutic Tumor Vaccines in Advanced Solid Tumors

Advanced solid tumors remain a major therapeutic challenge due to their complex heterogeneity and the immunosuppressive tumor microenvironment (TME). Although cancer vaccines are designed to induce long-lasting antitumor immunity, their efficacy is often limited by the TME's immune-evasive mechanisms.

Building on this rationale, investigators developed a novel vaccine comprising irradiated tumor cells and stromal cells isolated from adjacent non-cancerous tissues or tumor tissues in combination with adjuvant. Irradiated tumor cells in vaccines such as YMN102, YMN103, YMN104, YMN105, YMN106, and YMN107 are transfected with GM-CSF; the others, such as YMN101 and YMN108, are not transfected with GM-CSF. Preclinical studies across multiple tumor models have demonstrated potent antitumor activity with no significant toxicity observed following administration. This first-in-human Phase I study is designed to evaluate the safety and tolerability of this irradiated vaccine in patients with advanced solid tumors, alongside a preliminary assessment of its antitumor activity and immunogenic profile.

This is a first-in-human, Phase I, open-label study designed to evaluate the safety and tolerability of this novel vaccine. The study includes multiple arms targeting specific malignancies, including osteosarcoma, pancreatic cancer, HNSCC, colorectal cancer, HCC, glioma, and TNBC.

The primary objective is to determine the incidence of dose-limiting toxicities (DLTs). Secondary objectives include assessing the objective response, progression-free survival (PFS), and overall survival (OS) per RECIST v1.1. Exploratory analyses will monitor dynamic changes in circulating biomarkers and intratumoral immune modulation to identify potential predictive markers of clinical response.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Whole tumor cell-based vaccines provide a broad spectrum of tumor-associated antigens; however, their clinical utility is frequently limited by low intrinsic immunogenicity and an inability to overcome the immunosuppressive tumor microenvironment (TME). These limitations underscore the urgent need for strategies that can simultaneously enhance antigen presentation and modulate TME-mediated immune evasion.

The TME plays a pivotal role in shaping antitumor immunity. Non-malignant cellular components within the TME not only contribute to immune regulation and tumor progression but also interact dynamically with tumor-associated antigens. Leveraging these interactions may offer a unique opportunity to potentiate immune activation and improve vaccine efficacy.

Building on this rationale, investigators developed a novel vaccine comprising irradiated tumor cells and stromal cells isolated from adjacent non-cancerous tissues or tumor tissues in combination with adjuvant. Irradiated tumor cells in vaccines such as YMN102, YMN103, YMN104, YMN105, YMN106, and YMN107 are transfected with GM-CSF; the others, such as YMN101 and YMN108, are not transfected with GM-CSF. Preclinical studies across multiple tumor models have demonstrated potent antitumor activity with no significant toxicities observed following administration. This first-in-human Phase I study is designed to evaluate the safety and tolerability of this irradiated vaccine in patients with advanced solid tumors, alongside a preliminary assessment of its antitumor activity and immunogenic profile.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

54

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

  • Navn: Xingchen Peng, Professor
  • Telefonnummer: +86 18980606753
  • E-mail: pxx2014@163.com

Studiesteder

  • Kina
    • Sichuan
      • Chengdu, Sichuan, Kina, 610041
        • Rekruttering
        • West China Hospital, Sichuan University
        • Kontakt:
      • Chengdu, Sichuan, Kina, 610041
        • Ikke rekrutterer endnu
        • West China Hospital, Sichuan University
        • Kontakt:
          • Xingchen Peng, Professor
          • Telefonnummer: 13458502834
          • E-mail: pxx2014@163.com
        • Ledende efterforsker:
          • Xingchen Peng, Professor
        • Underforsker:
          • Hong Wu, Professor
        • Underforsker:
          • Dan Cao, Professor
        • Underforsker:
          • Lei Liu, Professor
        • Underforsker:
          • Xuelei Ma, Professor
        • Underforsker:
          • Ting Luo, Professor

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

Inclusion Criteria

  1. Histologically or cytologically confirmed advanced solid tumors, or radiologically diagnosed HCC, eligible for one of the following study parts based on tumor type, clinical status, and prior treatment history:

    Part A1: Patients with advanced osteosarcoma who achieved Stable Disease (SD) or Partial Response (PR) following first-line chemotherapy, and have at least one remaining lung metastatic lesion >= 0.5 cm.

    Part A2: Patients with advanced osteosarcoma who have relapsed, metastasized, or progressed following prior chemotherapy, or who are intolerant to the toxicities of previous systemic therapy.

    Part B1: Patients with advanced pancreatic cancer and disease progression following >= 1 prior line of standard systemic therapy.

    Part C1: Patients with advanced HNSCC and disease progression following >= 2 prior lines of systemic therapy.

    Part D1: Patients with advanced colon cancer and disease progression following >= 3 prior lines of therapy (including fluoropyrimidine, oxaliplatin, and irinotecan). Patients with RAS wild-type must have received EGFR inhibitors.

    Part E1: Patients with advanced hepatocellular carcinoma (HCC) and disease progression following >= 2 prior lines of systemic therapy.

    Part F1: Patients with advanced glioma and disease progression following the first-line Stupp regimen.

    Part G1: Patients with advanced pancreatic cancer and disease progression following >= 1 prior line of therapy.

    Part H1: Patients with advanced or recurrent metastatic breast cancer who have progressed on or after >= 3 prior lines of systemic therapy.

  2. Age 18-75 years.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
  4. Life expectancy > 3 months.

  5. Adequate organ function within 7 days prior to first dose, including:

    Hematologic: Hemoglobin (Hb) >= 80 g/L; White Blood Cell count (WBC) >= 3.0 x 10^9/L; Platelet count (PLT) >= 80 x 10^9/L; Absolute Neutrophil Count (ANC) >= 1.5 x 10^9/L.

    Hepatic: Total bilirubin <= 1.5 x ULN (<= 3 x ULN for liver metastases or HCC); ALT and AST <= 2.5 x ULN (<= 5 x ULN for liver metastases or HCC).

    Renal: Creatinine clearance > 60 mL/min (Cockcroft-Gault formula). Coagulation: International Normalized Ratio (INR) <= 1.5 x ULN.

  6. At least one measurable or evaluable lesion per RECIST v1.1.
  7. Ability to understand and sign written informed consent and comply with study procedures.

Exclusion Criteria

  1. Another primary malignancy within 5 years prior to first dose, except for adequately treated non-melanoma skin cancer, carcinoma in situ, or localized low-risk cancers.
  2. Active central nervous system (CNS) metastases or leptomeningeal disease.
  3. Positive for infectious diseases, including HIV, active Hepatitis C (HCV RNA positive), or active Hepatitis B (HBsAg or HBcAb positive with HBV DNA >= 500 IU/mL or >= 2000 copies/mL).
  4. Active pulmonary tuberculosis.
  5. Active autoimmune disease requiring systemic treatment within the past 2 years; or use of systemic corticosteroids (> 10 mg/day prednisone equivalent) within 4 weeks prior to first dose.
  6. Major surgery or significant trauma within 28 days prior to enrollment, or presence of unhealed wounds, ulcers, or conditions associated with high risk of bleeding or perforation.
  7. Arterial/venous thrombosis or pulmonary embolism within 6 months, or CTCAE Grade >= 3 bleeding event within 28 days prior to treatment.
  8. Localized conditions at the injection site (e.g., infection, inflammation, or extensive scarring) or clinically significant coagulation disorders that contraindicate subcutaneous or intraosseous administration.
  9. Known hypersensitivity or intolerance to study treatment components or related compounds.
  10. Pregnant or breastfeeding, or planning to conceive (participant or partner) during the study.
  11. Any condition that, in the investigator's judgment, may compromise safety or interfere with study participation or evaluation.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Osteosarcoma: YMN101(Part A1)
Participants will receive doses informed by the safety data and tolerability ranges established for analogous candidates in clinical studies. Patients with advanced osteosarcoma will be administered the vaccine via subcutaneous injection, with the immunization regimen consisting of a priming phase and a booster phase. Participants will be administered the corresponding doses according to a predefined allocation scheme and will complete the full vaccination cycle at prescribed time points per protocol.
Biologisk: YMN101
In the priming phase, subjects receive subcutaneous injections of the YMN101 vaccine on Days 0, 14, and 28. During the personalized immunotherapy (boost) phase, administration occurs every 28 days at the investigator's discretion.
Eksperimentel: Pancreatic cancer: YMN102 (Part B1)
Participants were assigned to different dose-level cohorts according to the order of enrollment, following a sequential escalation from low to high doses. Patients with advanced pancreatic cancer were administered the vaccine via subcutaneous injection, with the immunization regimen consisting of a priming phase and a booster phase. Dose escalation followed a standard 3+3 design to evaluate the safety and DLTs at each dose level. Participants received the assigned cell dose during the priming phase and completed subsequent administrations at predefined intervals according to the protocol.
Biologisk: YMN102
In the priming phase, subjects receive subcutaneous injections of the YMN102 vaccine on Days 0, 14, and 28. During the personalized immunotherapy (boost) phase, administration occurs every 28 days at the investigator's discretion.
Eksperimentel: Head and neck squamous cell carcinoma: YMN103 (Part C1)
Patients with advanced head and neck squamous cell carcinoma (HNSCC) will be vaccinated via subcutaneous injection. The immunization regimen encompasses a priming phase and subsequent booster phases. Participants will be administered the corresponding doses according to a predefined allocation scheme and will complete the full vaccination cycle at prescribed time points to evaluate the safety and tolerability.
Biologisk: YMN103
In the priming phase, subjects receive subcutaneous injections of the YMN103 vaccine on Days 0, 14, and 28. During the personalized immunotherapy (boost) phase, administration occurs every 28 days at the investigator's discretion.
Eksperimentel: Colon cancer: YMN104 (Part D1)
Patients with advanced colon cancer will be vaccinated via subcutaneous injection. The immunization regimen encompasses a priming phase and subsequent booster phases. Participants will be administered the corresponding doses according to a predefined allocation scheme and will complete the full vaccination cycle at prescribed time points to evaluate the safety and tolerability.
Biologisk: YMN104
In the priming phase, subjects receive subcutaneous injections of the YMN104 vaccine on Days 0, 14, and 28. During the personalized immunotherapy (boost) phase, administration occurs every 28 days at the investigator's discretion.
Eksperimentel: Hepatocellular carcinoma: YMN105 (Part E1)
Patients with advanced hepatocellular carcinoma (HCC) will be vaccinated via subcutaneous injection. The immunization regimen encompasses a priming phase and subsequent booster phases. Participants will be administered the corresponding doses according to a predefined allocation scheme and will complete the full vaccination cycle at prescribed time points to evaluate the safety and tolerability.
Biologisk: YMN105
In the priming phase, subjects receive subcutaneous injections of the YMN105 vaccine on Days 0, 14, and 28. During the personalized immunotherapy (boost) phase, administration occurs every 28 days at the investigator's discretion.
Eksperimentel: Glioma: YMN106 (Part F1)
Participants were assigned to different dose-level cohorts according to the order of enrollment, following a sequential escalation from low to high doses. Patients with advanced glioma received intracalvariosseous (ICO) injection of the vaccine. The immunization regimen consists of a priming phase and a booster phase. Dose escalation follows a standard 3+3 design to evaluate safety and DLTs at each dose level. Participants receive the assigned cell dose via intraosseous administration during the priming phase and complete subsequent administrations at predefined intervals according to the protocol.
Biologisk: YMN106
In the priming phase, subjects receive intracalvariosseous (ICO) injection of the YMN106 vaccine on Days 0, 14, and 28. During the personalized immunotherapy (boost) phase, administration occurs every 28 days at the investigator's discretion.
Eksperimentel: Pancreatic cancer: YMN107 (Part G1)
Participants were assigned to different dose-level cohorts according to the order of enrollment, following a sequential escalation from low to high doses. Patients with advanced pancreatic cancer were administered the vaccine via subcutaneous injection, with the immunization regimen consisting of a priming phase and a booster phase. Dose escalation followed a standard 3+3 design to evaluate the safety and DLTs at each dose level. Participants received the assigned cell dose during the priming phase and completed subsequent administrations at predefined intervals according to the protocol.
Biologisk: YMN107
In the priming phase, subjects receive subcutaneous injections of the YMN107 vaccine on Days 0, 14, and 28. During the personalized immunotherapy (boost) phase, administration occurs every 28 days at the investigator's discretion.
Eksperimentel: Breast cancer: YMN108 (Part H1)
Participants were assigned to different dose-level cohorts according to the order of enrollment, following a sequential escalation from low to high doses. Patients with advanced or recurrent metastatic breast cancer were administered the vaccine via subcutaneous injection, with the immunization regimen consisting of a priming phase and a booster phase. Dose escalation followed a standard 3+3 design to evaluate the safety and DLTs at each dose level. Participants received the assigned cell dose during the priming phase and completed subsequent administrations at predefined intervals according to the protocol.
Biologisk: YMN108
In the priming phase, subjects receive subcutaneous injections of the YMN108 vaccine on Days 0, 14, and 28. During the personalized immunotherapy (boost) phase, administration occurs every 28 days at the investigator's discretion.
Eksperimentel: Osteosarcoma: YMN101(Part A2)
Participants will receive doses informed by the safety data and tolerability ranges established for analogous candidates in clinical studies. Patients with advanced osteosarcoma refractory to prior chemotherapy will be administered the vaccine via subcutaneous injection with concomitant regorafenib, following a priming-booster immunization regimen. Participants will be administered the corresponding doses according to a predefined allocation scheme and will complete the full vaccination cycle at prescribed time points per protocol.
Biologisk: YMN101
In the priming phase, subjects receive subcutaneous injections of the YMN101 vaccine on Days 0, 14, and 28. During the personalized immunotherapy (boost) phase, administration occurs every 28 days at the investigator's discretion.
Medicin: Regorafenib
Regorafenib at 160 mg once daily from Day 1 to Day 21, every 4 weeks (Q4W).

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Tidsramme: From the first dose up to 14 days following the third dose (Day 0 to approximately Day 42).
DLT is defined as any Treatment-Related Adverse Event (TRAE) or clinically significant laboratory abnormality occurring during the DLT observation period. TRAEs include events judged by the investigator to be "definitely," "probably," or "possibly" related to the study treatment. Severity will be graded according to NCI-CTCAE v5.0.
From the first dose up to 14 days following the third dose (Day 0 to approximately Day 42).
Number of Participants Who Experienced an Adverse Event (AE)
Tidsramme: Up to 6 months from the date of the first dose.
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of the product was also an AE. The number of participants who experienced an AE was reported for each arm.
Up to 6 months from the date of the first dose.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Objective Response
Tidsramme: Up to 6 months from the date of the first dose.
Number of participants achieving a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR) according to RECIST v1.1. Due to the small sample size, data will be reported as absolute counts.
Up to 6 months from the date of the first dose.
Progression-Free Survival
Tidsramme: Up to 6 months from the date of the first dose.
Progression-Free Survival (PFS) is defined as the time interval from the start of treatment until the first documented occurrence of disease progression (PD) according to RECIST v1.1, or death due to any cause, whichever occurs first.
Up to 6 months from the date of the first dose.
Overall Survival
Tidsramme: Up to 12 months from the date of the first dose.
OS is defined as the time interval from the start of treatment to death due to any cause. For participants who are still alive at the end of the study, data will be censored at the last known date of follow-up.
Up to 12 months from the date of the first dose.

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

West China Hospital

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

15. maj 2026

Primær færdiggørelse (Anslået)

31. december 2026

Studieafslutning (Anslået)

30. juni 2027

Datoer for studieregistrering

Først indsendt

20. april 2026

Først indsendt, der opfyldte QC-kriterier

27. april 2026

Først opslået (Faktiske)

5. maj 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

6. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

4. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 2025-2774

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

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