Clinical trial NCT06857786: Postoperative Adjuvant Therapy for CT041 Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma Patients
Official title: Open Label, Multicenter, Phase Ib Trial of CT041, Claudin 18.2 Specific CAR T Cell Therapy As a Consolidation Therapy After Adjuvant Therapy for Resected Gastric or Gastroesophageal Junction Adenocarcinoma Patients
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Gastroesophageal Junction Adenocarcinoma
Gastric Adenocarcinoma
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2025-03-04
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Drug: CT041 autologous CAR T-cell injection
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and tolerability of satri-cel as consolidation therapy after postoperative adjuvant therapy in patients with resected gastric or gastroesophageal junction (G/GEJ) adenocarcinoma

Detailed description: The primary objective of this trial is to evaluate the safety and tolerability of satri-cel as consolidation therapy after postoperative adjuvant therapy in patients with G/GEJ adenocarcinoma. The primary endpoint is the frequency, type, severity and outcome of AE/SAE/AESI, which is the routine assessment indicators for evaluating the safety and tolerability of the investigational product in clinical trials.

Eligibility criteria: Inclusion Criteria:

* 1. Must have voluntarily signed the informed consent form (ICF) and be willing to comply with all trial procedures.

  2. Must be 18 -75 years old (inclusive), male or female. 3. Pathologically confirmed diagnosis of gastric/gastroesophageal junction (G/GEJ) adenocarcinoma.

  4. Must have CLDN18.2-positive tumor expression as determined by immunohistochemistry (IHC), defined as CLDN18.2 staining intensity ≥ 1+ in at least 70% of tumor cells.

  5. Must have undergone D2 gastrectomy and achieved R0 resection. 6. Must have pathological stage (y)pT4aN+ or (y)pT4bNany) according to the American Joint Committee on Cancer (AJCC) TNM Staging Classification (8th ed., 2017).

  7. Must have received full cycles of standard adjuvant chemotherapy according to treatment guidelines. Standard adjuvant chemotherapy allowed in this trial includes FLOT(docetaxel + oxaliplatin + fluorouracil), CapeOX (oxaliplatin + capecitabine), and FOLFOX(oxaliplatin + fluorouracil).
  1. Neoadjuvant chemotherapy is allowed.
  2. Participants who are deemed intolerable or medically improper to complete the full cycles of adjuvant chemotherapy or not beneficial as determined by the investigator could be eligible after discussing with the medical monitor.

     8. Must have no evidence of recurrent or metastatic G/GEJ adenocarcinoma. 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 7 days before leukapheresis).

     10. Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis.

     11. Laboratory results within 7 days before leukapheresis must meet the following criteria (Retesting once within one week is permitted. it will be considered a screening failure if retest still not meets the criteria): 12. Women of childbearing potential (WOCBP) must undergo a serum pregnancy test with negative result at screening and must be willing to use effective and reliable method of contraception for at least 12 months after the last satri-cel infusion. Egg donation should be refrained for 12 months.

     13. Male part

     Exclusion Criteria:

  <!-- -->

  1. The time interval between leukapheresis and completion of adjuvant chemotherapy is more than 12 weeks.
  2. Participants with high risk of bleeding, perforation or obstruction, including but not limited to deep or large ulcer, unstable/active ulcer, active or history of digestive tract bleeding/perforation/obstruction within three months.
  3. Participants who have received any non-standard adjuvant anti-tumor treatment for G/GEJ adenocarcinoma allowed in this trial, including any systemic anti-tumor drugs not specified in the protocol, any radiotherapy or interventional therapy, etc.
  4. Participants who have received systemic anti-tumor treatment for G/GEJ adenocarcinoma within 2 weeks (or within 5 half-lives of the drug, whichever is shorter) prior to leukapheresis.
  5. Participants who have received major surgery (excluding cataract surgery and others requiring local anesthesia) within 4 weeks prior to leukapheresis or significant traumatic injury and have not recovered adequately from the toxicity and/or complications. Participants who are anticipated to need major surgery during the trial will also be excluded.
  6. Participants who have received any prior genetic engineering modified cellular therapy (such as CAR T-cell, TCR T-cell, etc.).
  7. Participants with AEs from previous treatment who have not recovered to Grade ≤ 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, excluding hair loss, neuropathy, other events that are unlikely to cumulate toxicity from trial treatment as determined by the investigator, and laboratory abnormalities allowed in this trial.
  8. Participants with serologically positive human immunodeficiency virus (HIV), Syphilis, and hepatitis C virus (HCV). HCV antibody positive but HCV RNA negative can be enrolled.

Primary outcomes:
measure: Incidence, type, and severity of adverse events
timeFrame: Signed ICF to 15 years after CT041 infusion
Secondary outcomes:
measure: Disease-free survival (M12-DFS)
timeFrame: 12 months after surgery
measure: Disease-free survival (DFS) after surgery
timeFrame: Up to approximately 24 months
measure: Distant metastasis-free survival (DMFS) after surgery
timeFrame: Up to approximately 24 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 24 months
measure: To evaluate the cellular metabolism kinetics of satri-celrea under the curve (AUC) and sustained cell survival (Tlast) after satri-cel infusion
timeFrame: up to 18 months
measure: To evaluate the immunogenicity of satri-cel
timeFrame: up to 18 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Gaobo Hospital
state: Beijing
city: Nanjing
country: China
facility: Nanjing Gulou Hospital
state: Jiangsu
Study officials:
References: