Personalized immune-cell therapy targeting tumor-associated antigens

Tumor Associated Antigen-specific Engineered Immune Effector Cells (EIE) Against Cancer

This trial will try engineered immune cells made from a patient's own T cells to treat cancers that express specific tumor-associated antigens.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 1 Year to 80 Years
• Sex: All
• Sponsor: Shenzhen Geno-Immune Medical Institute (Academic / other)
• Drugs / interventions: chemotherapy, chimeric antigen receptor, immunotherapy
• Locations: 3 sites (Guangzhou, Guangdong and 2 other locations)
• Trial ID: NCT03535246 on ClinicalTrials.gov

What this trial studies

Researchers will collect a patient's immune cells, grow and engineer them in the lab to recognize tumor-associated antigens (including CAR-modified cells), and reinfuse them either into the bloodstream or directly into tumors. The Phase 1/2 design focuses first on safety and on the feasibility of manufacturing autologous engineered immune effector (EIE) cells, then on early signs of anti-tumor activity. Key measures include adverse events, success rate of generating EIE cells, and preliminary tumor response. The trial enrolls patients whose tumor specimens test positive for antigens such as GD2, mesothelin, Melan A, and members of the MAGE family at several centers in China.

Who should consider this trial

Good fit: Ideal candidates are patients whose tumors test positive for one or more specified tumor-associated antigens, have ECOG performance status 0–2, adequate organ and marrow function, and can provide cells for autologous manufacturing.

Not a fit: Patients whose tumors do not express the target antigens, who have inadequate organ or marrow function, are pregnant, or have very limited life expectancy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could eliminate tumor cells expressing the target antigens and produce tumor shrinkage or longer survival for some patients.

How similar studies have performed: Adoptive T-cell and CAR-T therapies have produced strong remissions in certain blood cancers, but results in solid tumors have been mixed and targeting tumor-associated antigens in solid tumors remains an active but not yet proven area.

Eligibility criteria

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.

  3\. 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.

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

  8\. 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.

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.

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

  6\. 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.

Where this trial is running

Guangzhou, Guangdong and 2 other locations

• QiFu Hospital of Guangzhou University of Chinese Medicine — Guangzhou, Guangdong, China (Recruiting)
• Shenzhen Geno-immune Medical Institute — Shenzhen, Guangdong, China (Recruiting)
• Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center — Kunming, Yunnan, China (Recruiting)

Study contacts

• Study coordinator: Lung-Ji Chang, PhD

Conditions Cancer; immunotherapy; T cell; Gene therapy