A phase II multi-institutional single arm trial evaluating TG4010 vaccine plus nivolumab in non-small cell lung cancer.
The combination of TG4010 and nivolumab showed limited benefit in NSCLC, with only 1 of 12 evaluable patients responding and a median overall survival of 7.23 months.
Where it sits
this study against the rest of the lixisenatide corpusSummary and findings
This study evaluated the safety and activity of TG4010 vaccine plus nivolumab in non-small cell lung cancer (NSCLC) patients. The trial aimed to enroll 29 patients but was terminated early after 13 patients were enrolled. One of 12 evaluable patients responded to treatment, with a median overall survival of 7.23 months.
Abstract
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.
Background
This paper addresses the efficacy of combining TG4010, a mucin 1 vaccine, with nivolumab, an immune checkpoint inhibitor, in treating non-small cell lung cancer (NSCLC). Prior research indicated that immune checkpoint inhibitors have transformed NSCLC therapy, yet only 25% of patients achieve durable responses. Understanding the potential of TG4010 in this context is crucial, especially given its previous demonstration of activity in NSCLC.
Methods
This was a multi-institutional, single-arm trial with a target accrual of 29 evaluable patients. The study enrolled ICI naïve NSCLC patients and was designed to assess the safety and activity of the combination therapy. The primary endpoint was the response rate, requiring at least 10 out of 29 responders. The treatment was administered until early termination due to slow patient accrual.
Results
The primary endpoint was not met, with only 1 of 12 evaluable patients responding, equating to an 8.3% response rate. The median overall survival was reported as 7.23 months. Among the 13 enrolled patients, 2 had disease control while 9 experienced disease progression.
Interpretation
The findings indicate limited clinical benefit from the combination of TG4010 and nivolumab in NSCLC, as evidenced by the low response rate and short median overall survival. This contrasts with previous studies that have shown more promising results with immune checkpoint inhibitors alone. The small sample size and early termination of the study limit the robustness of these conclusions, suggesting that further research is necessary to explore potential benefits in specific patient populations or in combination with other therapies.
Key findings
- 1 of 12 (8.3%) evaluable patients responded to treatment.
- Median overall survival was 7.23 months.
- 2 patients had disease control, and 9 progressed on therapy.
- The study was terminated early after enrolling 13 patients.
Limitations
- Study terminated early due to slow accrual.
- Small sample size with only 13 enrolled patients.
- Limited evaluable patients (n=12) for response assessment.
- No evidence of T cell clonal expansion or epitope spreading.