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    Analysis

    Can immunotherapy crack solid tumours? The 2026 debate

    Most cancers are solid tumours, where engineered T cells face scarce targets, a hostile microenvironment and heterogeneous cells.[1] In 2025-2026 several trials crossed long-standing thresholds, including a phase 3 win for a personalised mRNA vaccine and the first solid-tumour CAR-T approval, but the absolute gains and toxicity costs remain debated.[2][3][4]

    Editor reviewedStrict sourcingUpdated Cancer immunotherapyHealth and medicineLife sciences
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    Checkpoint inhibitors already treat many solid tumours, but most patients do not respond, and cell therapies have mostly been limited to blood cancers.[5][6] This page sets out what the 2025-2026 evidence shows and how it can be read. It does not offer medical advice.

    The obstacles

    NCI identifies three barriers for CAR T cells in solid tumours: few suitable surface antigens, an immunosuppressive tumour microenvironment, and molecular variation between and within tumours.[1] Tumours also escape immunity by becoming less visible and by displaying proteins that switch immune cells off.[7] A 2019 estimate found that 43.6% of US cancer patients were eligible for checkpoint inhibitors in 2018 but only about 12.5% would respond.[5]

    What changed in 2025-2026

    In a randomised phase 2 trial of 156 patients with claudin-18.2-positive gastric cancer, satri-cel extended median progression-free survival to 3.25 months versus 1.77 months (hazard ratio 0.37).[8] China approved it in June 2026, described as the first CAR-T approval for a solid tumour.[3] Grade 3 or higher adverse events occurred in 99% of satri-cel patients and cytokine release syndrome in 95%.[4]

    The 1,137-patient INTerpath-001 trial of intismeran autogene plus pembrolizumab met its recurrence-free and distant metastasis-free survival endpoints in resected melanoma, according to Merck and Moderna; effect sizes were not yet public.[2][9] BioNTech ended a phase 2 colorectal trial of autogene cevumeran monotherapy after an overall-survival imbalance.[10]

    Akeso reported that ivonescimab, a PD-1 x VEGF bispecific, extended median overall survival to 30.8 months versus 22.6 months with pembrolizumab in PD-L1-positive lung cancer.[11] The T-cell engager tarlatamab extended overall survival in small cell lung cancer to 13.6 months versus 8.3 months with chemotherapy.[12] Zanidatamab plus tislelizumab improved overall survival in HER2-positive gastroesophageal cancer.[13]

    How to read the evidence

    The strongest solid-tumour results came from adding something to an existing backbone or using a new mechanism with a clear target: a vaccine on top of pembrolizumab, a bispecific that folds VEGF inhibition into PD-1 blockade, and a T-cell engager against DLL3.[2][11][12] The colorectal vaccine trial, by contrast, tested the vaccine alone, which suggests (but does not prove) that vaccines may need a checkpoint partner.[10]

    Satri-cel’s approval is a regulatory first, but a median gain of about six weeks in progression-free survival, with near-universal severe adverse events, is a modest trade-off. It shows that solid-tumour CAR-T can beat standard care in a randomised trial, not that the core obstacles are solved.[8][4][1]

    Several headline results (INTerpath-001, HARMONi-2) are known so far from company statements and conference data, so effect sizes, subgroup consistency and overall-survival maturity should be checked against full publications.[9][11]

    What to expect next

    The FDA decision on ivonescimab due by 14 November 2026 will be a key US test for PD-1 x VEGF bispecifics; an approval would likely accelerate the competing BioNTech and Bristol Myers Squibb programme.[14][15] Full INTerpath-001 data and regulatory filings are likely in the next 6-12 months, and their effect size will shape whether personalised vaccines expand beyond melanoma.[9] Uncertainty is high: in vivo CAR-T and solid-tumour cell therapies remain at an early, toxicity-limited stage.[16][4]

    Competing views

    Combinations are breaking through

    Randomised wins in 2025-2026 for a vaccine plus pembrolizumab, a PD-1 x VEGF bispecific and a claudin-18.2 CAR-T show solid tumours are yielding to smarter combinations and new targets.[2][11][8]

    Gains are real but modest and costly

    Absolute benefits are often small, toxicity can be heavy, only a minority respond to checkpoint drugs, and some flagship programmes have failed.[4][5][10]

    Biology remains the bottleneck

    Until the antigen, microenvironment and heterogeneity problems are solved, cell therapies will help narrow subsets of solid-tumour patients.[1][8]

    Questions readers ask

    Why are solid tumours harder for immunotherapy than blood cancers?

    For CAR-T, NCI cites three obstacles in solid tumours - few suitable surface antigens, an immunosuppressive tumour environment and variation between and within tumours.[1]

    Is there now an approved CAR-T for a solid tumour?

    In China, yes. The NMPA approved satri-cel in June 2026 for claudin-18.2-positive, HER2-negative advanced gastric cancer. It is not FDA-approved.[3]

    How large was satri-cel's benefit?

    In its randomised trial, median progression-free survival was 3.25 months versus 1.77 months with physician's choice of therapy, and grade 3 or higher adverse events occurred in 99% of satri-cel patients.[8][4]

    Did personalised cancer vaccines succeed in solid tumours?

    Results split in August 2026. Intismeran autogene plus Keytruda met its phase 3 endpoints in resected melanoma, while BioNTech stopped a colorectal monotherapy trial of autogene cevumeran after an overall-survival imbalance.[2][10]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      NCI identifies three obstacles for CAR T cells in solid tumours: few suitable surface antigens, an immunosuppressive tumour environment, and molecular variation between and within tumours. confirmedas of 2025-02-26

    2. [2]

      Merck and Moderna announced on 19 August 2026 that the 1,137-patient phase 3 INTerpath-001 trial of intismeran autogene plus Keytruda in resected stage IIB-IV melanoma met its primary endpoint of recurrence-free survival and key secondary endpoint of distant metastasis-free survival versus Keytruda alone. confirmedas of 2026-08-19

    3. [3]

      In June 2026 China's NMPA approved CARsgen's satri-cel for claudin-18.2-positive, HER2-negative advanced gastric or gastro-oesophageal junction cancer, described as the first CAR T-cell therapy approved for a solid tumour. confirmedas of 2026-09-01

    4. [4]

      In the satri-cel trial, grade 3 or higher adverse events occurred in 99% of satri-cel patients versus 63% of controls, and cytokine release syndrome in 95% of treated patients. confirmedas of 2026-06-22

    5. [5]

      A 2019 study estimated that 43.6% of US patients with cancer were eligible for checkpoint inhibitors in 2018 but only about 12.5% would respond to them. confirmedas of 2019-05-03

    6. [6]

      In April 2024 the FDA required a boxed warning on six approved BCMA- or CD19-directed autologous CAR-T products for the risk of T-cell malignancies, and said patients should be monitored life-long for secondary cancers. confirmedas of 2024-04-18

    7. [7]

      According to NCI, cancer cells can escape the immune system through genetic changes that make them less visible, surface proteins that switch off immune cells, and changes to the normal cells around the tumour. confirmedas of 2026-10-10

    8. [8]

      In a randomised phase 2 trial of 156 patients with previously treated claudin-18.2-positive gastric or gastro-oesophageal junction cancer, the CAR-T therapy satri-cel extended median progression-free survival to 3.25 months versus 1.77 months with physician's choice (hazard ratio 0.37). confirmedas of 2025-06-01

    9. [9]

      Merck and Moderna reported no new safety signals in INTerpath-001 and said they plan to present the data at a medical meeting and engage regulators on filings; full results had not been published as of the announcement. confirmedas of 2026-08-19

    10. [10]

      On 28 August 2026 BioNTech ended a phase 2 trial of autogene cevumeran monotherapy in resected colorectal cancer after its data monitoring board saw a numerical overall-survival imbalance between arms; the pancreatic cancer trial IMcode003 continues. confirmedas of 2026-08-28

    11. [11]

      Akeso reported in September 2026 that its PD-1 x VEGF bispecific ivonescimab extended median overall survival to 30.8 months versus 22.6 months with pembrolizumab in first-line PD-L1-positive non-small cell lung cancer in the HARMONi-2 trial (hazard ratio 0.73). confirmedas of 2026-09-13

    12. [12]

      In the phase 3 DeLLphi-304 trial of 509 patients, tarlatamab extended median overall survival to 13.6 months versus 8.3 months with chemotherapy (hazard ratio 0.60), with fewer grade 3 or higher adverse events (54% vs 80%). confirmedas of 2025-07-24

    13. [13]

      On 25 August 2026 the FDA approved zanidatamab, a HER2-targeted bispecific antibody, with the PD-1 inhibitor tislelizumab for first-line HER2-positive gastroesophageal adenocarcinoma; median overall survival was 26.4 versus 19.2 months (hazard ratio 0.72). confirmedas of 2026-08-25

    14. [14]

      The FDA accepted Summit Therapeutics' application for ivonescimab plus chemotherapy in EGFR-mutated non-squamous non-small cell lung cancer after TKI therapy, with a decision goal date of 14 November 2026. confirmedas of 2026-01-29

    15. [15]

      On 2 June 2025 BioNTech and Bristol Myers Squibb agreed to co-develop the PD-L1 x VEGF-A bispecific BNT327, with $1.5 billion upfront, $2.0 billion in anniversary payments through 2028 and up to $7.6 billion in milestones. confirmedas of 2025-06-02

    16. [16]

      All five ESO-T01 patients had grade 3 or higher adverse events, four had cytokine release syndrome, one patient died from lesion-related spinal cord compression, and the trial was stopped early in 2025. confirmedas of 2026-04-01

    Revision history (1)
    1. Page created.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "Can immunotherapy crack solid tumours? The 2026 debate." ContentLora, updated Oct 10, 2026. https://contentlora.com/analysis/solid-tumor-immunotherapy-debate

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