A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer

Launched by CARINA BIOTECH LIMITED · Feb 26, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called CNA3103, which uses specially modified immune cells (called CAR-T cells) to target colorectal cancer that has spread to other parts of the body. The main goal of the study is to see how safe this treatment is and how well it works for patients with metastatic colorectal cancer. To participate, patients must be 18 years or older, have been diagnosed with this type of cancer, and have had limited previous treatments. They will also need to have a specific marker (LGR5) present in their tumors, which will be checked through a biopsy.

Participants in the trial can expect to undergo several procedures, including a blood collection to gather their immune cells and a short course of chemotherapy to prepare their body for the treatment. After receiving an infusion of CNA3103, patients will be monitored for safety and effectiveness over the next two years. It's important to note that participants will need to attend regular follow-up visits during this time. This trial is currently recruiting patients, and it's a chance for those with limited options to potentially benefit from a novel therapy.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Signed written Informed Consent.
• • Male and female subjects aged greater than or equal to18 years.
• • Eastern Cooperative Oncology Group (ECOG) Performance Score 0 to 1.
• • Histologically or cytologically confirmed metastatic colorectal cancer previously treated with no more than 2 prior fluoropyrimidine, oxaliplatin, and/or irinotecan-based regimens for metastatic disease in the palliative setting. Neoadjuvant/adjuvant treatment of resectable oligometastatic disease, does not count as a prior line of therapy in the palliative setting unless there is development of an unresectable local or distant recurrence within 6 months of its last dose.
• • Subjects who discontinue their prior regimen due to toxicity (in the absence of disease recurrence/progression) will also have their prior therapy count as one prior regimen. Anti-Kirsten rat sarcoma virus (Anti-KRAS) agents are also allowable. The planned lymphodepletion start date must be at least 4 weeks from last chemotherapy, biologic, radiotherapy, or investigational therapy (excluding bridging therapy), with resolution of all lingering toxicities to Grade ≤ 1, with the exception of neuropathy and alopecia.
• • Subjects previously treated in the adjuvant/neoadjuvant setting with an oxaliplatin/irinotecan regimen, who develop an unresectable local recurrence and/or metastatic disease within 6 months of the date of last oxaliplatin/irinotecan chemotherapy will have their adjuvant/ neoadjuvant therapy count as one prior regimen.
• • Positive for any level of LGR5 expression in tumor biopsies.
• • Measurable or evaluable disease per RECIST version 1.1.
• • Life expectancy of at least \>12 weeks.
• • Normal organ and marrow function.
• • No clinically significant abnormalities in urinalysis results at Screening.
• • No known clinically significant gastrointestinal disease within 28 days prior to enrolment.
• • No ongoing requirement for anti-diarrheal therapy.
• • For female subjects of childbearing potential and male subjects with partners of childbearing potential, agreement (by subject and/or partner) to use a highly effective form of contraception and to continue its use for 6 months after the last dose of IP.
• • Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to CNA3103 administration.
• Exclusion Criteria:
• • Inability to comply with study and follow-up procedures.
• • Women who are pregnant or lactating.
• • Has BRAF-mutated colorectal cancer.
• • Has received trifluridine/tipiracil (TAS-102) or regorafenib for metastatic disease.
• • Treatment with chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or radiation therapy as cancer therapy (excluding bridging therapy) within 4 weeks prior to the lymphodepletion start date.
• • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent in the previous 28 days prior to enrolment.
• • Have received antibody-based therapies within the previous 28 days or 5 half-lives of the agent, whichever is shorter.
• • Major surgery, in the previous 4 weeks prior to enrolment.
• • Clinically detectable pleural effusion requiring drainage in the 4 weeks prior to enrolment.
• • Any uncontrolled medical or psychiatric risk factors which would contraindicate the use or impair the ability of the subject to provide informed consent, receive protocol therapy or may impose excessive risk to the subject.
• • Known central nervous system (CNS) disease.
• • Current use of medications that may have the potential of QTc prolongation.
• • Uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy.
• • Has a known infection with human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, alcoholic or other hepatitis, or cirrhosis.
• • Inability to be venipunctured and/or tolerate venous access.
• • Second malignancies within 5 years prior to enrollment, except for those with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent.
• • Active autoimmune disease that is not controlled by non-steroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of ≤10 mg/day prednisone.
• • History of inflammatory bowel disease (active or past) or active peptic ulcer disease.
• • History of connective tissue disorders.
• • History of chronic leukemias.
• • History of previous, whole abdomen radiation therapy (or total pelvic radiation therapy) or more than Grade 1 residual toxicity from previous radiation therapy.
• • High cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year
• • Left ventricular ejection fraction \<50%.
• • Have had a venous thromboembolic event requiring anticoagulation.
• • Congenital or acquired long QT syndrome.
• • QTc prolongation.
• • History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
• • Patients with ascites, previous drainage of ascites, peritoneal caking, and/or significant peritoneal deposits at Baseline are excluded from participation in the study
• • Patients with reduced liver reserves and/or possibility of hepatobiliary complications, including, but not limited to; portal hypertension, liver resection (segmentectomy, metastasectomy) in the previous 6 months, patients with existing biliary stents or the need to receive a biliary stent to relieve bile duct obstruction of any etiology, patients with cholelithiasis, patients who abuse alcohol or paracetamol (with or without concomitant alcohol abuse), patients who use herbal medicines, and patients with substance abuse.