Clinical Study of Novel Therapeutic Vaccine for Advanced Solid Tumors
ConditionMalignant Tumor
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorWest China Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 18-75 years.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
Life expectancy > 3 months.
At least one measurable or evaluable lesion per RECIST v1.1.
Disqualifiers
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.
Active central nervous system (CNS) metastases or leptomeningeal disease.
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).
Active pulmonary tuberculosis.
Trial design
Design model
Parallel
Treatments tested in this trial
YMN101
Biological/VaccineIn 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.
YMN102
Biological/VaccineIn 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.
YMN103
Biological/VaccineIn 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.
YMN104
Biological/VaccineIn 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.
YMN105
Biological/VaccineIn 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.
YMN106
Biological/VaccineIn 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.
YMN107
Biological/VaccineIn 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.
YMN108
Biological/VaccineIn 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.
Regorafenib
DrugRegorafenib at 160 mg once daily from Day 1 to Day 21, every 4 weeks (Q4W).
Treatment groups
54 Participants
are divided into 9 treatment groups9
Treatment groupsSee each treatment group below.
Group A: Osteosarcoma: YMN101(Part A1)Experimental treatment 1 intervention
Group B: Pancreatic cancer: YMN102 (Part B1)Experimental treatment 1 intervention
Group C: Head and neck squamous cell carcinoma: YMN103 (Part C1)Experimental treatment 1 intervention
Group D: Colon cancer: YMN104 (Part D1)Experimental treatment 1 intervention
Group E: Hepatocellular carcinoma: YMN105 (Part E1)Experimental treatment 1 intervention
Group F: Glioma: YMN106 (Part F1)Experimental treatment 1 intervention
Group G: Pancreatic cancer: YMN107 (Part G1)Experimental treatment 1 intervention
Group H: Breast cancer: YMN108 (Part H1)Experimental treatment 1 intervention
Group I: Osteosarcoma: YMN101(Part A2)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
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.
Time frame
From the first dose up to 14 days following the third dose (Day 0 to approximately Day 42).2
Number of Participants Who Experienced an Adverse Event (AE)
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.
Time frame
Up to 6 months from the date of the first dose.Secondary outcomes
1
Objective Response
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.
Time frame
Up to 6 months from the date of the first dose.2
Progression-Free Survival
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.
Time frame
Up to 6 months from the date of the first dose.3
Overall Survival
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.
Time frame
Up to 12 months from the date of the first dose.Sponsors and contacts
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Source ClinicalTrials.gov