Evaluating the safety of IMC002 for advanced digestive system tumors

A Phase I, Open-label, Multi-center, Dose-escalation Study to Evaluate the Safety, Feasibility, and Preliminary Efficacy of IMC002 in Patients With Claudin18.2-positive Advanced Digestive System Tumors

This study is testing a new treatment called IMC002 to see if it is safe and effective for people with advanced digestive system tumors like gastric and pancreatic cancers.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Suzhou Immunofoco Biotechnology Co., Ltd (Industry-sponsored)
• Drugs / interventions: CAR-T, prednisone, chemotherapy, cyclophosphamide, fludarabine
• Locations: 7 sites (Beijing, Beijing and 6 other locations)
• Trial ID: NCT05946226 on ClinicalTrials.gov

What this trial studies

This open-label, multi-center, dose-escalation clinical study aims to assess the safety, feasibility, and preliminary efficacy of IMC002 in patients with CLDN18.2 positive advanced digestive system tumors, including gastric and pancreatic cancers. Approximately 9-18 patients will be enrolled in three dose escalation cohorts, receiving autologous IMC002 treatment after undergoing leukapheresis and lymphodepletion chemotherapy. Patients will be monitored closely for safety and efficacy, with follow-up periods extending up to 15 months. The study will help determine the optimal dosing and safety profile of IMC002 in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with advanced CLDN18.2 positive digestive system tumors who have failed previous standard of care treatments.

Not a fit: Patients with digestive system tumors that do not express CLDN18.2 or those who have not undergone prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced digestive system tumors that express CLDN18.2.

How similar studies have performed: While this approach is novel in the context of CLDN18.2 positive tumors, similar CAR-T cell therapies have shown promise in other cancer types.

Eligibility criteria

Inclusion Criteria:

* Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures
* Age \> 18 and ≤70 years
* Patients with histologically or cytologically confirmed locally advanced/metastatic digestive system tumors including but not limited to advanced gastric cancer at least failed two lines of SOC, esophagogastric junction adenocarcinoma, and advanced pancreatic cancer failed at least one line SOC;
* Must have CLDN18.2 positive tumor expression histologically as determined by IHC (defined as positive rate of tumor cells≥40% and staining intensity ≥2+ ) or a biopsy if archived tumor sample is not available; representative tumor samples (primary or metastatic, archived or newly collected) are expected to be obtained
* Expected survival time ≥12 weeks
* Measurable or evaluable disease per RECIST1.1
* ECOG performance status score of 0-1
* Adequate organ and bone marrow function. If any laboratory test results are abnormal with reference to the criteria below, a repeat test can be performed within 1 week. If the test results are still abnormal, the patient fails screening.
* Recovery to grade 0-1 from AEs related to prior anticancer therapy or to an acceptable level for inclusion/exclusion criteria except alopecia and vitiligo
* Female of childbearing age must undergo a serum pregnancy test with negative results at screening and infusion; Female of childbearing age or male patients whose sexual partners are females of childbearing age are willing to take medically approved high-efficiency contraceptive measures such as intrauterine devices or condoms from the time of signing the informed consent to 1 year after infusion (women of childbearing age include premenopausal women and women within 24 months of post menopause).

Exclusion Criteria:

* Pregnant and lactating women
* Human immunodeficiency virus (HIV) antibody positive; acute or chronic active hepatitis B; acute or chronic active hepatitis C Hepatitis. Syphilis antibody positive; cytomegalovirus (CMV) infection; Epstein-Barr (EB) virus infection.
* Active or clinically poorly controlled serious infections
* Uncontrollable pleural effusion, pericardial effusion and ascites effusion existed before enrollment.
* Extensive or diffuse lung or liver metastases
* Oxygen saturation ≤95% without oxygen inhalation
* With other diseases that may limit their participation in this study, such as pulmonary embolism, chronic obstructive pulmonary disease, symptomatic or poorly controlled interstitial lung disease, or clinically significant abnormal lung function tests
* Known prior or current hepatic encephalopathy requiring treatment; patients with current or history of central nervous system (CNS) disease. Autoimmune diseases; CNS metastases or meningeal metastases with clinical symptoms, or other evidence that the patient's CNS or meningeal metastases have not been controlled, and are judged not suitable for the study by the investigator
* Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure \> 100 mmHg after standardized antihypertensive drug treatment); not well controlled diabetes mellitus \[fasting plasma glucose (FPG) ≥10.2mmol/L\].
* Presence of any of clinical cardiac symptoms or disorders
* Evidence of major coagulopathy or other significant bleeding risk
* Systemic steroids equivalent to \>15mg/day prednisone within 2 weeks before leukapheresis, except inhaled or topic steroids
* Requiring systemic therapy with corticosteroids or other immunosuppressive drugs during the treatment period. Presence of any active autoimmune disease, or history of autoimmune disease expect recur.
* Previous or concomitant other malignancies
* Have received other gene therapies including but not limited to any CAR-T and TCR-T therapy
* Anti-tumor therapies other than for the pretreatment and bridging therapies \< 5 half-lives or 28 days (whichever is shorter) prior to study treatment
* Any investigational drugs or study drugs from a previous clinical study within 30 days prior to signing the informed consent; traditional Chinese medicine with anti-tumor activities within 2 weeks prior to the study treatment
* History of serious allergic disease or known allergy to any component of the study treatments
* With severe mental disorders
* Any issue that would impair the ability of the patient to receive or tolerate the planned treatment, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Where this trial is running

Beijing, Beijing and 6 other locations

• Chinese PLA General Hospital — Beijing, Beijing, China (Recruiting)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (Not_yet_recruiting)
• The First Affiliated Hospital of Xiamen University — Xiamen, Fujian, China (Not_yet_recruiting)
• Shandong Cancer Hospital — Jinan, Shandong, China (Not_yet_recruiting)
• Renji Hospital, Shanghai Jiaotong University School of Medicine — Shanghai, Shanghai, China (Not_yet_recruiting)
• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Not_yet_recruiting)
• First Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Jianming Xu, Pro. — Chinese PLA General Hospital
• Study coordinator: Jianming Xu, Pro.

Conditions Advanced Digestive System Tumor