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Lung Neoplasms / Immune Checkpoint Inhibitors / Carcinoma, Non Small Cell Lung · Journal article
Oncoimmunology · September 2, 2026
Early or partial results. Treat as a signal, not a conclusion.
This phase 2 single-arm trial of TG4010 vaccine plus nivolumab in ICI-naïve NSCLC was terminated early after enrolling only 13 patients (target 29) and demonstrated limited clinical activity. Although the combination was well tolerated, the primary endpoint of response rate was not met, with only 1 of 12 evaluable patients responding (8.3%), yet mechanistic analyses revealed immune pathway activation and identified an exceptional responder with baseline interferon signaling upregulation.
Phase 2 multi-institutional single-arm trial. ICI-naïve patients with non-small cell lung cancer across multiple academic cancer centers in California and Texas. Intervention: Nivolumab plus TG4010 vaccine (modified Vaccinia virus Ankara expressing MUC1 antigen and IL-2). n = 13. Multi-institutional: UC Davis Health (Sacramento), UC San Diego, UC San Francisco, City of Hope Medical Center (Duarte), MD Anderson Cancer Center (Houston), Indiana University School of Medicine (In….
Response rate: 1 of 12 evaluable patients (8.3%) achieved response Disease control: 2 patients with disease control; 9 progressing on therapy Median overall survival: 7.23 months
Safety: Most common adverse effects were fatigue (grades 1–3) and injection site reactions (grades 1–2)
The combination of TG4010 and nivolumab showed insufficient benefit in unselected ICI-naïve NSCLC and did not meet the primary endpoint. However, the identification of a durable responder with elevated interferon signaling suggests potential value in molecularly selected subsets or in combination with cytotoxic therapy, warranting further hypothesis-driven investigation.
Early-phase single-arm trial terminated early due to slow accrual with only 13 enrolled patients, showing limited clinical benefit (8.3% response rate) but providing mechanistic insights into immune response that warrant further investigation.
As stated by the source record.
Quoted from the source exactly as published.
The combination of TG4010 and nivolumab showed insufficient benefit in unselected ICI-naïve NSCLC and did not meet the primary endpoint. However, the identification of a durable responder with elevated interferon signaling suggests potential value in molecularly selected subsets or in combination with cytotoxic therapy, warranting further hypothesis-driven investigation.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) therapy, but only 25% of patients have durable responses. TG4010, a mucin 1 (MUC1) vaccine, has demonstrated activity in NSCLC. We conducted a multi-institutional study to determine the safety and activity of nivolumab plus TG4010 in ICI naïve NSCLC patients (NCT02823990). The target accrual was 29 evaluable patients. The primary endpoint was the response rate requiring at least 10/29 responders. The study was terminated early due to slow accrual after enrolling 13 patients. The treatment was well tolerated. The most common adverse effects were fatigue (grades 1-3) and injection site reactions (grades 1-2). TG4010+ICI had limited benefit in NSCLC with 1 of 12 (8.3%) evaluable patients responding, 2 with disease control, and 9 progressing on therapy. The median overall survival was 7.23 months. One patient with a HER2 driver mutation (which prognosticates poor ICI response) achieved an ongoing durable complete response. This exceptional responder had significant baseline upregulation of GSEA pathways linked to interferon signaling, which may be critical for generating vaccine directed immune responses. In general, therapy decreased MUC1 expression in tumors and PD-1 on T cells and upregulated pathways of adaptive and innate immune responses within tumors and circulating immune cells. However, TCR sequencing demonstrated no T cell clonal expansion or epitope spreading, which may explain the lack of clinical benefit. TG4010+ICI appears to have limited benefit. Further study is needed to optimize the clinical efficacy, which may include a role in NSCLC with driver mutations or in combination with cytotoxic therapy.
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