Patient case: 68-year-old male with non-small cell carcinoma; genetic feature: MET

Clinical trial: A Phase I Clinical Study for Evaluating the Safety and Efficacy of MASCT-I in Patients With Advanced Solid Tumors

Summary: The purpose of this study is to determine whether the MASCT-I alone and in combination with chemotherapy drug are safe and effective in the treatment of advanced bladder cancer and soft tissue sarcoma

Detailed description: The multiple-antigen specific cell therapy which was developed by Hengrui Yuanzheng is optimized continuously and has been upgraded from the first-generation MASCT technology to MASCT-I. MASCT-I is to add PD1 antibody in vitro cell culture process of MASCT technology to block PD1 receptor on immunocytes, relieving the brake at immunocytes' reinfusion and interaction with tumor cells for enhancing the effectiveness of immunocytes killing tumor cells. At present, the development and validation of manufacturing process has been completed, and it is urgently needed to conduct the validation of clinical effect. This study is primarily to assess the safety and anti-tumor effect of MASCT-I technology to provide a basis for II/III phase clinical trials.
  This is a single-center,phase I clinical study for evaluating the safety and efficacy of MASCT-I technology in patients with advanced solid tumors and preliminarily assessing the antitumor effectiveness of MASCT-I alone and in combination with chemotherapy drugs. About 33-36 cases of adult patients with advanced solid tumors (only limited to bladder cancer and soft tissue sarcoma ) are to be recruited.
  This study is divided into two stages:
  Stage I is a small sample safety observation stage where the "3+3" design including groups A and B. Group A represents the group of MASCT-I alone where patients with advanced solid tumors that various standard therapies failed in clinical practice are included;Group B represents the combination group of MASCT-I plus chemotherapy drug or group of MASCT-I alone where patients with recurrent or metastatic advanced solid tumor who achieved the clinical benefit after chemotherapy (CR, PR, SD) are included.
  Stage II is a dose expansion stage to observe the safety and anti-tumor effectiveness. The patients enrolled in the stage II are the same in group B subjects.

Eligibility: Major Inclusion Criteria:
  -  written informed consent
  -  Life expectancy≥ 6 months
  -  Scored 0 -1 on ECOG
  -  Results of blood test and biochemistry at baseline meeting the following criteria:Hemoglobin≥85g/L,Leucocyte≥3.0×109/L,Absolute neutrophil count（ANC）≥1.5×109/L，Trombocyte≥70×109/L,ALT/AST ≤ 2.5×ULN or ≤ 5×ULN for patients with hepatic metastases, ALP≤2.5 times of upper limit of normal, Serum total bilirubin < 1.5×ULN,Serum urea nitrogen and creatinine ≤ 1.5×ULN, Serum albumin ≥30g/L
  -  The following criteria should also be met by the patients in Group A;
  1. Patients who suffer from advanced (unresectable) or recurrent solid tumors (only limited to bladder cancer and soft tissue sarcoma) confirmed by histology and cytology and are treated unsuccessfully with various standard therapies.
  2. According to RECIST1.1 criteria, there must be one measurable focus;
  3. Time interval between end of other anti-tumor measures and this study treatment is at least 1 month;
  -  Patients to be enrolled in group B should also meet the following criteria:
  1. Bladder cancer: confirmed by histology and cytology, advanced recurrent or metastatic. GP chemotherapy could realize clinical benefit.
  2. Soft tissue sarcoma: confirmed by histology and cytology, advanced recurrent or metastatic.Clinical benefit could be achieved after MAID or CAV/IE first-line chemotherapy with predominant Doxorubicin.
  Note: Clinical benefits referred to that patients reached the complete remission (CR), partial remission (PR) or stable disease (SD) after treatment.
  Major Exclusion Criteria:
  -  Participation in the planning or implementation of this study (including the employees of HRYZ and the staff of the study center);
  -  Enrollment for another clinical study at the same time, unless it is an observational (non-interventional) clinical study;
  -  Possibility of receiving other systemic anti-tumor treatment during this study;
  -  Being pregnant or planning to become pregnant;
  -  Refusal to provide blood samples;
  -  Known allergy to sodium citrate;
  -  A medical history of allogenic organ transplantation (including bone marrow transplantation and peripheral stem cell transplantation, but excluding corneal transplantation);
  -  Subjects who present clinical symptom of central nervous system metastases (such as encephaledema, need of hormone intervention or brain metastasis progression);
  -  Subjects who are using immunosuppressant, or systemic, or absorbable local steroid therapy for the purpose of immunosuppression;
  -  Subjects who previously received MASCT or other cellular immunotherapy;
  -  Active tuberculosis;
  -  Any major operation (to be defined by the investigator) within 28 days before administration of the first investigational treatment;
  -  Active infections, including hepatitis B, hepatitis C and human immunodeficiency virus (HIV) infection;
  -  Presence of peripheral nervous system disorders, or a history of apparent metal disorders and central nervous system disorders;
  -  Severe hepatic (e.g., liver cirrhosis, etc.), renal, respiratory diseases, or non-communicable diseases such as uncontrolled diabetes, hypertension, etc.;
  -  Other malignant tumors within the last five years, excluding non-melanoma skin cancer and carcinoma in situ.

Relevance to patient case: not relevant