Immunotherapy Based on Tumor Associated Antigen-specific Immune Effector Cells

Phase 1

• Conditions: Cancer
• Interventions: Biological: Engineered Immune Cells

• Registration Number: NCT03535246
• Lead Sponsor: Shenzhen Geno-Immune Medical Institute

Brief Summary

The primary objectives are to evaluate the safety and efficacy of infusion of autologous tumor associated antigen-specific engineered immune effector cells (EIE).

Detailed Description

Malignant tumor is still a major challenge in medicine and requires technology breakthrough, and its mortality rate is the highest among all diseases. World Health Organization and the American Cancer Association expect about 12 million new cancer patients worldwide each year, with about 8 million cancer deaths (20 thousand cancer deaths per day). At present, more than 20 million people are suffering from cancer, and this figure will increase to 75 million in 2030. In Asia, the incidence of cancer is expected to rise by 60% in 2020, and the number of cancer related deaths will reach 7 million annually in 2030. The incidence of lung, Intestine, breast, prostate and gastric cancer is high, and lung, Intestine, breast and liver cancer are the main causes of cancer related deaths in Asia.

Adoptive immunotherapy based on cytotoxic T lymphocytes reactive with specific antigens has proven to be effective. In vitro induction of tumor antigen-specific immune cells and engineering of target specific immune cells have great potential for cancer eradication. The study aims to evaluate the safety and efficacy of ex vivo manipulated EIE cells including chimeric antigen receptor (CAR) modified immune cells in treating cancer. The primary study objectives are to evaluate the safety of the investigational product, autologous EIE cells, to subjects by intravenous and intratumoral injection. The secondary study objectives are (1) to evaluate the success rate of generating autologous EIE cells ex vivo, and (2) to determine the anti-cancer efficacy of the EIE cells.

Study Timeline

• Study First Submitted: 2018-05-10
• Study First Submitted QC: 2018-05-13
• Study First Posted: 2018-05-24
• Study Start: 2018-07-01
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-18
• Last Update Posted: 2019-09-19
• Primary Completion: 2021-06-30
• Study Completion: 2021-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• 1. Written, informed consent obtained prior to any study-specific procedures. 2. The results of immune staining of the patient's cancer specimens positive for any one or more of tumor-associated antigens, such as GD2, mesothelin, P16, MMP, Melan A, MAGE A1, MAGE A3, and MAGE A4.

  2. Eastern Cooperative Oncology Group (ECOG) PS of 0, 1 or 2. 4. Life expectancy ≥ 3 months. 5. Able to comply with the protocol. 6. Histologically confirmed and documented high risk International Federation of Gynecology and Obstetrics (FIGO): Stage III-IV.

  3. Not pregnant, and on appropriate birth control if of childbearing potential.

  4. Adequate bone marrow reserve with

  • absolute neutrophil count (ANC) ≥ 1000/mm3.
  • Platelets ≥100,000/mm3. 9. Adequate renal and hepatic function with
  • Serum creatinine ≤ 2 x upper limit of normal (ULN).
  • Serum bilirubin ≤ 2 x ULN.
  • aspartate aminotransferase (AST)/ALT ≤ 2 x ULN.
  • Alkaline phosphatase ≤ 5 x ULN.
  • Serum bilirubin. 2.0 is acceptable in the setting of known Gilbert's syndrome.

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Exclusion Criteria

• 1. The results of immune staining of the patient's tumor-associated antigens are all negative.

  2. Previous experience of other cell therapy. 3. Participation in any other cell therapy protocols within one year. 4. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug.

  3. Minor surgical procedures within 2 days prior to Day 0 (including central venous access device placement for chemotherapy administration, tumor biopsies, needle aspirations).

  4. Pregnant or lactating females. 7. Unable to comply with the trial related requirement. 8. Inadequate bone marrow function:

  • Absolute neutrophil count < 1.0 x 10e9/L.• Platelet count < 100 x 10e9/L.• Hb < 9 g/dL.

Inadequate liver and renal function:

• Serum (total) bilirubin > 1.5 x ULN.

• AST & ALT > 2.5 x ULN (> 5 x ULN in patients with liver metastases).

• Alkaline phosphatase > 2.5 x ULN (or > 5 x ULN in case of liver metastases or > 10 x ULN in case of bone metastases).

• Serum creatinine >2.0 mg/dl (> 177 μmol/L).

• Urine dipstick for protein uria should be < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate < 1 g of protein/24 hr.

  9. Serious active infection requiring i.v. antibiotics at during screening. 10. Subject infected with HIV (HIV antibody positive), Treponema pallidum antibody positive or TB culture positive.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single arm	Engineered Immune Cells	EIE cells to treat cancer.

Primary Outcome Measures

Name	Time	Method
percentage of adverse effects after EIE cell injection	up to one month	To assess the safety of autologous EIE cells in vivo. The percentage of patients who have adverse effects will be evaluated by using the NCI CTCAE V4.0 criteria.

Secondary Outcome Measures

Name	Time	Method
Rate of successful EIE generation	up to one month	The percentage of successful EIE generation, which are derived from subjects and pass the safety test after standard culture procedures, viable for at least one preparation, will be evaluated.
Ability of EIE cells to induce anti-cancer reaction	after 1 month from EIE cells infusion until 12 months after infusion	measurement of TAA concentration in blood sample
Ability of EIE cells for anti-cancer reaction	after 1 month from EIE cells infusion until 24 months after infusion	Objective response (complete response (CR) + partial response (PR)) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Trial Locations

Locations (3)

Shenzhen Geno-immune Medical Institute; 🇨🇳 ShenZhen, Guangdong, China

QiFu Hospital of Guangzhou University of Chinese Medicine; 🇨🇳 GuangZhou, Guangdong, China

Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center; 🇨🇳 KunMing, Yunnan, China