National Colorectal Cancer Awareness Month 2025: Looking Back at Progress for Cell Therapy
In observance of National Colorectal Cancer Awareness Month, held annually in March, we took a look back at news in cell therapy for colorectal cancer indications.
According to the Colorectal Cancer Alliance, colorectal cancer is the second deadliest cancer in the United States. In 2025 alone, 52,900 people in the US are expected to die from colorectal cancer. Although screening efforts and lifestyle changes have helped to reduce death rates during the past few decades, substantial unmet need remains, especially for patients who's disease was diagnosed in later stages.
An important areas of interest for new therapeutic development in colorectal cancer is cell therapy. A number of companies and academic institutions are now pursuing the development of chimeric antigen receptor T-cell (CAR-T) therapy and other such advanced treatments for colorectal cancers. In honor of National Colorectal Cancer Awareness Month, observed annually in March by the patient and clinician communities, CGTLive® is taking a look back at the progress that was made for cell therapy in colorectal cancer over the past year. Click the "READ MORE" buttons for more details and information about each item.
Metastatic Colorectal Cancer CAR-T Therapy GCC19CART Demonstrates Safety and Clinical Activity in US Patients
June 4, 2024 — GCC19CART (Innovative Cellular Therapeutics), an investigational autologous CAR-T therapy, has demonstrated safety and clinical activity among patients with refractory metastatic colorectal cancer being treated in the phase 1 CARAPIA-1 clinical trial (NCT05319314). The data were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31 to June 4, in Chicago, Illinois.
As of the December 31, 2023 data cutoff, 5 patients had been treated with GCC19CART in CARAPIA-1, which is taking place in the United States. The group includes 4 patients who were treated at dose level 1 (1x106 cells/kg, DL1) and 1 patient who was treated at dose level 2 (2x106 cells/kg, DL2), all of whom had reached the end of the 30 day dose limiting toxicity timeframe. The overall response rate was 40%, with 2 of 5 patients having achieved a partial response to the CAR-T. Furthermore, first author Benjamin L. Schlechter, MD, an instructor in medicine at Harvard Medical School and gastrointestinal oncologist at Dana-Farber Cancer Institute, and colleagues, noted that 1 other patient showed stable disease with a partial metabolic response observed on their PET/CT scan. In the 2 other treated patients, progressive disease was observed; although, it was noted that a falling tumor marker suggesting tumor flare was reported in 1 of these patients.
In terms of safety, cytokine release syndrome (CRS) was reported in all 5 patients, with 2 patients (40%) having grade 1 cases of CRS and 3 patients (60%) having grade 2 cases of CRS. Four of the 5 patients experienced cases of diarrhea, with 1 patient (20%) having a grade 1 case, 2 patients (40%) having grade 2 cases, and 1 patient (20%) having a grade 3 case. A single grade 2 case of immune effector cell-associated neurotoxicity syndrome occurred in 1 patient (20%). The aforementioned adverse events (AEs) constituted the most common AEs related to the CAR-T product and all were noted to have resolved with therapy.
A2 Bio’s Trial for Solid Tumor Tmod CAR-T A2B694 Doses First Patient
May 19, 2024 — The first patient has been dosed in A2 Biotherapeutics (A2 Bio)’s phase 1/2 EVEREST-2 clinical trial (NCT06051695) evaluating A2B694, an investigational logic-gated Tmod CAR-T therapy, in patients with mesothelin (MSLN)-expressing solid tumors that have lost HLA-A*02 expression.
EVEREST-2 is recruiting patients with solid tumors with MSLN-expression, including lung cancer, colorectal cancer, pancreatic cancer, ovarian cancer, and mesothelioma cancers. Patients must have previously participated in the company’s BASECAMP-1 screening study (NCT04981119) that is identifying patients with solid tumors that are positive for somatic human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH). The Tmod approach is intended to allow the CAR-T to selectively kill tumor cells while sparing healthy tissue by conferring the CAR T-cells with an “activator” that targets MSLN and a “blocker” that protects cells that do not have HLA-A*02 LOH.
“Dosing our first patient in this trial is a key step to provide a precise, novel CAR-T therapy to patients with solid tumors that express mesothelin with no curative treatment options,” William Go, MD, PhD, the chief medical officer of A2 Bio, said in a statement. “Sadly, current treatment options for these patients are palliative and limited by toxicity in the recurrent, unresectable, locally advanced or metastatic setting. All of us at A2 Bio would like to thank participating patients, investigators, and clinical care providers.”
Maria Pia Morelli, MD, PhD, on Adapting ctDNA and MRD Negativity Into Solid Tumor Cell Therapy Research
February 5, 2024 — CGTLive spoke with Maria Pia Morelli, MD, PhD, assistant professor, department of gastrointestinal (GI) medical oncology, division of cancer medicine, MD Anderson Cancer Center, The University of Texas, to learn more about research that she is working on with cell therapy in solid tumors, particularly GI cancers. She shared that research with solid tumors has started to use circulating tumor DNA and minimal residual disease, markers that originated and are mainly used within the fields of hematological malignancies, as markers within solid tumor research. She also discussed a trial she is leading at MD Anderson that uses natural killer cells with cetuximab in earlier stages of colorectal cancer.
Triumvira Immunologics’ TAC T-cell Therapy TAC01-CLDN18.2 to be Evaluated in Phase 1/2 Clinical Trail for Solid Tumors
January 19, 2024 — Triumvira Immunologics’ TAC01-CLDN18.2, an investigational autologous T-cell antigen coupler (TAC) CLDN18.2-targeted T-cell product, is set to be evaluated in the first-in-human phase 1/2 TACTIC-3 (NCT05862324) clinical trial for patients with various types of solid tumors. Triumvira recently presented a poster detailing the design of the dose escalation and dose expansion clinical trial at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers (GI) Symposium, held January 18-20, in San Francisco, California.
TAC01-CLDN18.2 integrates TAC, Triumvira’s proprietary chimeric receptor that is intended to activate and direct T-cells against tumor cells. TAC01-CLDN18.2 specifically expresses the CLDN18.2 TAC with the intention of targeting tumor cells that are CLDN18.2-positive. The TACTIC-3 trial is currently recruiting patients with gastric cancer, gastroesophageal cancer (GEJ), esophageal adenocarcinoma (AC), non–small cell lung cancer (NSCLC), cholangiocarcinoma, pancreatic ductal AC (PDAC), ovarian mucinous cancer, and colorectal cancer.
The phase 1 dose escalation portion of the study will follow a standard 3+3 design and aims to treat 9 to 24 patients in total. Four different dose levels will be evaluated: 1-3x105 cells/kg, 6-8x105 cells/kg, 1-3x106 cells/kg, and 6-8x106 cells/kg. Patients with gastric cancer, GEJ, esophageal AC, NSCLC, PDAC, cholangiocarcinoma, ovarian mucinous cancer, and colorectal cancer are eligible for this portion of the trial. These participants must have cancer that is negative for expression of HER2 and must have had at least 2 lines of prior therapy.
