Key 2025 ASCO® Outcomes

Bottlenecks to Cell Therapy Success in Solid Tumors

As reflected in 2025 ASCO® Annual Meeting theme “Driving Knowledge to Action: Building a Better Future”, innovation with CAR-Ts in solid tumors has been oriented for treatment precision within selected tumors apiece. However, CAR-T cell therapy in solid tumors has progressed from “hopeful” to “complicated” based on the recent presentations made at 2025 ASCO® Annual Meeting.

1. Manufacturing lag kills momentum

• Unmodified CLDN18.2 CAR-T (CT041/Satri-cel) in gastric cancer improved mOS to 7.9 vs. 5.5 months with chemo (HR-0.69, N=156), but a significant proportion of patients (~16%) dropped out during the ~4–6-week vein-to-vein window. Additionally, durability of responses was poor, with half of the responders progressing by 6 months in the Phase I cohort.^1,2

2. Logic gates for safety (finally) show promise

• Hypoxia-activated CEA CAR-Ts hit a 47% ORR (N=15); LOH-gated MSLN CAR-Ts hit 20% (N=5) in NSCLC. Side effects are contained though results remain tumor-specific, and a pH-sensitive HER2 CAR-T in breast cancer fizzled with 0% RR.^3-5

3. Improving delivery method isn’t a magic bullet

• GBM trials tested intra-cranial delivery (to improve cell delivery and potentially reducing systemic toxicity) of dual‐target EGFR/IL13Rα2 CAR-T and CARv3-TEAM-E T (producing anti-EGFR TEAM). Safety was solid, but poor objective responses of around 0–8% (N = 7 to13).^6-7

4. Repeat dosing doesn’t guarantee effectiveness

• Intracranial B7-H3 CAR-T (no lymphodepletion), on day 14 with 6–7 monthly “boosters” improved mOS to 13.5 months in 10 patients, but over 80% experienced tumor inflammation–associated neurotoxicity (TIAN).⁸

5. “Armored” CAR-Ts pack cytokine payloads… and toxicity.

• GPC3-targeted CAR-Ts in HCC and CEA-CAR-Ts in CRC show ORRs of ~42–56% (N<10), but Grade ≥ 3 CRS, colitis and hematologic toxicities spike. Fragile late-stage patients may not survive the super-charged immune storm^9-10

Bottom line: ASCO® Annual Meeting delivered a portfolio of innovative CAR-T constructs that achieved modest advances alongside significant setbacks. Only by resolving these key operational and clinical hurdles will one be able to predict the strategic impact of cell therapies in solid tumors. Look out for our next analysis of key themes.

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Abbreviations- Satri-cel: Satricabtagene autoleucel; ICV: intracerebroventricular; CEA: Carcinoembryonic Antigen; MSLN: Mesothelin; TEAM: T-cell–engaging antibody molecule

References

1. Qi C et al., 2025 ASCO® Annual Meeting Abstract # 4003
2. Peng H et al., 2025 ASCO® Annual Meeting Abstract #4015
3. Wei S et al., 2025 ASCO® Annual Meeting Abstract #8517
4. Punekar S et al., 2025 ASCO® Annual Meeting Abstract # 3040
5. Sun M et al., 2025 ASCO® Annual Meeting Abstract # 1025
6. Gerstner ER et al., ASCO® ASCO Annual Meeting Abstract #2017
7. Bagley S et al, 2025 ASCO® Annual Meeting Abstract #102
8. Li G et al., 2025 ASCO® Annual Meeting Abstract #2018
9. Fan J et al., 2025 ASCO® Annual Meeting Abstract #4084
10. Schlechter B et al., 2025 ASCO® Annual Meeting Abstract #3581