ASCO 2025 | Clinical Progress of CAR-T for Solid Tumors

There are not many ASCO 2025 abstracts focused on CAR-T for solid tumors, and those with clinical data are even fewer. Most of the research is led by Chinese companies, including CARsgen, Immunofoco, Innovative Cellular Therapeutics(ICT), and Shanghai Cell Therapy Group.

CARsgen’s CT041

CARsgen’s Claudin18.2 CAR-T, CT041 (Shureki Olorensai Injection), is well known in the industry and is the most advanced CAR-T pipeline for solid tumors globally. 

Recently, CARsgen published a summary on ASCO's website detailing the results of its Phase II clinical trial in China targeting advanced gastric and gastroesophageal junction cancer (CT041-ST-01, NCT04581473). This trial is notable for being the world’s first confirmatory randomized controlled trial in solid tumor CAR-T therapy. 

From March 29, 2022, to August 16, 2024, a total of 156 subjects were randomized to receive either CT041 (n=104) or TPC (n=52). Of those in the TPC group, 20 subjects later received CT041 treatment.

In the ITT (intent-to-treat) population: According to IRC evaluation, CT041 significantly improved PFS (median PFS 3.25 vs. 1.77 months), meeting the primary endpoint, with a 63% reduction in the risk of disease progression or death. OS also showed a clear trend of benefit (mOS 7.92 vs. 5.49 months).

In the mITT (modified intent-to-treat) population: Among the 136 subjects who actually received treatment (CT041 group: 88; TPC group: 48), the mPFS was 4.37 vs. 1.84 months, a 70% reduction in disease progression/death risk; mOS was 8.61 vs. 5.49 months, a 40% reduction in death risk. 

For the 20 TPC patients who later received CT041, mOS reached 9.20 months. Across all 108 patients who received CT041 (88 from CT041 group, 20 from TPC), mOS reached 9.17 months, while the 28 TPC-only patients had an mOS of only 3.98 months. 

CT041 showed good overall safety with only 4 cases of grade 3 CRS, and no grade 4-5 CRS or any ICANS events.

Immunofoco’s EpCAM CAR-T

Immunofoco, which showcased two solid tumor CAR-Ts (IMC001 and IMC002) at ASCO 2024, returned this year with early Phase I clinical data for EpCAM CAR-T IMC002. The study aimed to assess safety and efficacy in GI cancers (including gastric and colorectal).

As of April 30, 2023, 25 patients were screened for EpCAM expression, 4 were excluded due to low expression. 8 CRC and 13 GC patients received treatment. 

IMC002 showed good safety, with no treatment-related deaths during the 4-week follow-up. Two high-dose patients (4.8%) experienced DLT; 9 patients (43%) had grade 1-3 CRS. Encouraging efficacy was observed in gastric cancer: ORR of 23.5%, DCR of 70.6%. 

The study also emphasized the role of antigen presentation and NK T-cell activation in mediating CAR-T response.

Innovative Cellular Therapeutics (ICT)’s Non-Viral GCC19CART

Innovative Cellular Therapeutics (ICT) disclosed early data from the Phase 1 clinical trial of its solid tumor CAR-T candidate, GCC19CART, in the United States. GCC19CART is ICT’s first clinical candidate developed based on the universal CoupledCAR? platform technology for solid tumors. GCC19CART targets GCC (Guanylyl Cyclase C), which is stably expressed in primary colorectal cancer (CRC) cells and upregulated in metastatic CRC cells, making it a specific marker for CRC. It has been developed to treat relapsed/refractory metastatic CRC. Clinical trials of GCC19CART are ongoing in both China and the U.S.
This update covers the U.S. Phase 1 trial data, which aims to evaluate the safety and efficacy of GCC19CART in U.S. CRC patients. As of January 23, 2025, nine patients have been treated with GCC19CART. All subjects experienced cytokine release syndrome (CRS) at grades 1-2; 2 out of 9 developed immune effector cell-associated neurotoxicity syndrome (ICANS). One patient in dose level 2 (DL2) experienced dose-limiting toxicity and died 48 days after infusion.
The overall response rate (ORR) in dose level 1 (DL1, n=4) was 25% (1 out of 4 achieved partial response, PR); in dose level 2 (DL2, n=5), the ORR was 80% (4 out of 5, including 3 PRs and 1 pathological complete response). The PR in DL1 was observed at month 2, while in DL2, 3 out of 4 PRs were observed by month 1, demonstrating dose-dependent tumor killing activity.
At data cutoff, 2 patients in DL2 maintained remission; one patient achieved a complete metabolic response by PET at month 2 and maintained PR by CT at month 6, with continuous tumor shrinkage (38.33% at month 1, 40.77% at month 2, 82.58% at month 4, and 75.61% at month 6). Another patient maintained PR at month 6 but progressed at month 8.
The median progression-free survival (PFS) was 5.0 months in DL1 and 7.8 months in DL2. The median duration of response was 2.2 months in DL1 and 6.9 months in DL2. The study report indicates a potential trend of improved safety and efficacy of GCC19CART in the U.S. study compared to previous trials conducted in China.

Shanghai Cell Therapy Group’s Non-Viral MSLN CAR-T

Shanghai Cell Therapy Group released an ASCO abstract reporting preliminary Phase 1 data for its autologous CAR-T candidate BZT2312. This therapy targets MSLN and self-secretes a PD-1 nanobody. It was developed using the JL-Lightning? ultra-rapid, culture-free, non-viral CAR-T manufacturing platform, which enhances CAR-T stemness, in vivo expansion, and persistence. BZT2312 can be manufactured in just 30 hours.

The Phase 1 study enrolled patients with malignant pleural mesothelioma (MPM) who had failed standard treatments and showed MSLN and PD-L1 expression on tumors as confirmed by IHC. Seven advanced MPM patients were enrolled and received a single dose of CAR-T cell infusion. In Dose Level 1 (DL1), 1 patient achieved a partial response (PR), with a disease control rate (DCR) of 75% (3/4). In Dose Level 2 (DL2), 3 patients achieved an objective response rate (ORR) of 100% (3/3), including 1 patient who reached complete response (CR) at 3 months and maintained it for over 9 months.

Regarding safety: In DL1, 1 of 4 patients experienced Grade 1 cytokine release syndrome (CRS), with no immune effector cell-associated neurotoxicity syndrome (ICANS) or dose-limiting toxicities (DLT). In DL2, 2 of 3 patients experienced Grade 3–4 CRS, but no ICANS. Two cases of Grade 3 immune-mediated pneumonitis occurred and were managed with clinical intervention strategies. All patients experienced Grade 3–4 hematologic toxicities, which were reversible with supportive care.

A2 Bio’s Logic-Gated CAR-T

A2 Biotherapeutics (A2 Bio) is a U.S.-based clinical-stage cell therapy company focused on developing logic-gated cell therapies using its proprietary Tmod? platform, designed to selectively target tumor cells while sparing normal cells. 

At ASCO 2025, A2 Bio presented two abstracts reporting early clinical data from its Tmod CAR-T candidates.

CEA Tmod CAR-T 

A2B530 is a logic-gated CAR-T therapy targeting CEA, developed via the Tmod? platform. It utilizes an activating receptor targeting CEA and an inhibitory receptor recognizing HLA-A*02 to differentiate tumor cells from normal ones. 

The EVEREST-1 clinical trial enrolled patients with unresectable locally advanced or metastatic solid tumors expressing CEA and exhibiting loss of heterozygosity (LOH) at the HLA locus. As of January 15, 2025, 14 patients had been enrolled. 

Results showed good tolerability, with neutropenia reaching its lowest point between days 7–10 post-infusion and recovery observed in all patients. No dose-limiting toxicities (DLTs), grade >3 serious adverse events (AEs), or related neurotoxicities were reported. One patient in dose level 2 (DL2) experienced a possible grade 2 cytokine release syndrome (CRS) on day 15, which resolved within two days with supportive care; the diagnosis was later confounded by a positive blood culture. The low incidence of CRS corresponded with low serum cytokine levels within 28 days post-infusion. 

A2B530 demonstrated signs of clinical activity and dose responsiveness. Among six evaluable patients in DL1–2, one partial response (PR) was observed in three pancreatic cancer patients. Peak expansion data also suggested a possible dose-response trend.

MSLN Tmod CAR-T 

A2B694 is a logic-gated CAR-T therapy targeting MSLN, also developed via the Tmod? platform, utilizing a CAR against MSLN and an inhibitory receptor targeting HLA-A*02.

It is being evaluated in the EVEREST-2 clinical trial, enrolling patients with recurrent, unresectable locally advanced or metastatic solid tumors expressing MSLN and HLA LOH. As of January 15, 2025, five patients had been enrolled. 

The study reported good tolerability, with no DLTs, CRS, or related neurotoxicity. One patient was hospitalized due to decreased appetite. No long-term toxicities were observed within 7.5 months post-infusion. 

A2B694 was detectable in peripheral blood in all infused patients. Additionally, a pancreatic cancer patient showed detectable levels of A2B694 in a tumor biopsy taken 42 days post-infusion.

Summary

Solid tumor CAR-T therapy faces many challenges: tumor antigen heterogeneity, immunosuppressive microenvironment, off-target effects, poor CAR-T homing, and T-cell exhaustion. While companies are using various technologies to address these issues, progress remains slow. Nonetheless, China remains at the forefront globally in the research and development of CAR-T for solid tumors.

Reference

[1]. https://www.asco.org/abstracts-presentations/ABSTRACT492772

[2]. https://www.asco.org/abstracts-presentations/ABSTRACT495584
[3].https://www.asco.org/abstracts-presentations/ABSTRACT5090965

[4]. https://www.asco.org/abstracts-presentations/ABSTRACT4944846

[5]. https://www.asco.org/abstracts-presentations/ABSTRACT5035987

[6]. https://www.asco.org/abstracts-presentations/ABSTRACT503930