Salivary gland cancer (SGC) is rare and has various histological types. This rarity and heterogeneity have hindered elucidation of the therapeutic contribution of systemic therapy, including immune checkpoint inhibitors, to recurrent or metastatic SGC (RM-SGC). The purpose of this trial was to investigate the efficacy and safety of nivolumab for platinum-refractory RM-SGC. This phase II trial for platinum-refractory RM-SGC was conducted at nine centers. Nivolumab 240mg was administered intravenously every 2weeks. The primary endpoint was the objective response rate (ORR), and secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Twenty-four patients were enrolled between March 2018 and January 2022. The main histological types were salivary duct carcinoma (n =10), adenoid cystic carcinoma (n =6), and adenocarcinoma not otherwise specified (n =5). The ORR was 8.3% (2/24, 80% CI, 2.2-20.6), with two partial responses in patients with salivary duct carcinoma. The DCR was 29.2% (7/24), while all of the other 17 patients (70.8%) showed progressive disease on first disease evaluation at 12weeks. With a median follow-up of 21.2months, median PFS and OS were 3.0months (95% CI, 2.8-3.2) and 25.0months (95% CI, 10.9-39.1), respectively. There were no new safety concerns with nivolumab monotherapy. This phase II trial of nivolumab for patients with platinum-refractory RM-SGC did not meet its primary endpoint of ORR. Although nivolumab may be worth further development in salivary duct carcinoma, these results may raise concerns over nivolumab monotherapy for RM-SGC.

Nivolumab has become an essential therapeutic agent for patients with advanced or recurrent gastric cancer. However, the impact of metastatic patterns on its clinical efficacy has not been fully elucidated. This study aimed to clarify the association between distinct metastatic patterns and outcomes of nivolumab monotherapy. Ninety-two patients with advanced or recurrent gastric cancer who received nivolumab were retrospectively analyzed. Clinicopathological variables, including performance status, HER2 expression, and predominant metastatic pattern, were correlated with survival outcomes and response rates. The median observation period was 48.3 months. The median overall and progression-free survival for the entire cohort were 5.80 and 2.43 months, respectively. Patients with ECOG performance status 2-3 had significantly shorter survival than those with PS 0-1. HER2-positive status was associated with longer PFS. When stratified by metastatic pattern, the lymph node metastasis group showed markedly longer survival (median OS 35.1 months, PFS 11.9 months) than the peritoneal (OS 4.66, PFS 2.36 months) and hematogenous/other groups (OS 5.80, PFS 2.10 months). The objective response and disease control rates were also significantly higher in the lymph node group. The pattern of metastatic spread, particularly lymphatic involvement, appears to influence the efficacy of nivolumab in advanced or recurrent gastric cancer. Recognizing metastatic patterns may assist in optimizing patient selection and therapeutic strategies for immune checkpoint blockade.

BackgroundThe efficacy of nivolumab for advanced renal cell carcinoma (aRCC) has been evaluated in real-world evidence (RWE) studies across several European countries, yet data from Spain have been lacking.Patients and methodsWe conducted a multicenter, retrospective study of 222 previously treated aRCC patients to assess the efficacy of nivolumab and the influence of pre-treatment factors on clinical outcomes across 13 Spanish centers. Eligible patients had received at least one dose of nivolumab in routine clinical practice. Demographic, clinical, and laboratory data were extracted from electronic records. Efficacy endpoints were overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and overall response rate (ORR). Survival estimates were calculated by the Kaplan–Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Factors associated with disease control (DC) and response were tested with logistic regression in univariable and multivariable analyses. Comparisons between patient and disease characteristics were carried out using Fisher’s exact test. All P values were two-sided, and those < 0.05 were considered statistically significant. Results were contextualized with key clinical experiences involving nivolumab monotherapy in aRCC.ResultsWith a median follow-up of 14.6 months, median overall survival (OS) was 18.1 months (95% confidence interval [CI], 14.2–23.7 months), and median progression-free survival (PFS) was 4.96 months (95% CI, 3.98–7.13). The disease control rate was 51% (95% CI, 45–58%), and the objective response rate was 23% (95% CI, 18–30%). Poor International Metastatic RCC Database Consortium (IMDC) risk score was independently associated with shorter OS, while prior nephrectomy predicted improved OS. Poor IMDC risk and ≥ 3 metastatic sites were independently associated with shorter PFS; ≥ 3 metastatic sites also correlated with reduced disease control.ConclusionConsistent with previous clinical trials and RWE studies, our findings reinforce the efficacy of nivolumab in routine clinical practice for an unselected cohort of previously treated aRCC patients in Spain.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-025-15264-9.

Oral Malignant Melanoma Achieving Long-Term Survival With Nivolumab Monotherapy Following Surgical Treatment: A Report of a Rare Case

Colorectal cancer is a heterogeneous disease, where therapy is chosen based on the presence or absence of predictive and prognostic markers, leading to a higher degree of treatment individualization with the aim of maximizing clinical benefit. In general, microsatellite-unstable tumors are characterized by high sensitivity to immunotherapy. A small percentage of patients with rectal cancer are diagnosed with microsatellite-unstable disease, and immunotherapy therefore represents a potentially curative option. We present a case report of a 34year-old patient with microsatellite-unstable locoregionally advanced rectal cancer who was treated with nivolumab monotherapy. The therapy led to a rapid response, with almost complete clinical remission of the primary tumor reported after only 3 months of therapy. After 6 months of nivolumab therapy, complete clinical remission of the disease was identified, and the patient is currently in a watch-and-wait mode as part of non-surgical management of the disease. The observed toxicity was consistent with the known toxicity profile of immunotherapy and did not lead to discontinuation of therapy. Our case report highlights the need to test for predictive markers in patients with locoregionally advanced rectal cancer in order to identify specific subtypes of the disease that can be treated with immunotherapy with a high probability of achieving clinical complete remission, thereby avoiding potentially risky surgery.

This study aimed to investigate the effects of concomitant proton pump inhibitor (PPI) use on the effectiveness of nivolumab in Japanese patients with advanced gastric cancer. A single-center, retrospective, observational study was conducted at Keio University Hospital, Japan. We reviewed the medical records of consecutive patients with advanced gastric cancer treated with nivolumab monotherapy between September 2017 and March 2024 and compared treatment efficacy and safety with or without the concomitant use of PPIs. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Univariable and multivariable Cox proportional hazards models were used to estimate the hazard ratio (HRs) and 95% confidence intervals (CIs). Of the 84 patients included in this study, 46 were treated with PPIs. The median PFS was 2.1 (95% CI, 1.4-3.3) months in the PPI group and 4.4 (95% CI, 1.8-6.6) months in the non-PPI group (crude HR, 1.84; 95% CI, 1.15-2.95). The corresponding median OS was 5.3 (95% CI, 3.2-7.3) months and 7.3 (95% CI, 5.6-18.1) months (crude HR, 1.78; 95% CI, 1.10-2.89). Multivariable analysis revealed that PPI use significantly shortened both PFS and OS (adjusted HR, 1.79; 95% CI, 1.08-2.97 and adjusted HR, 1.72; 95% CI, 1.03-2.86, respectively). Concomitant use of PPI may reduce the effectiveness of nivolumab in patients with advanced gastric cancer.

Follistatin-like 1 (FSTL1) has been demonstrated to be a key molecule in cancer intractability associated with immune exhaustion and dysfunction, and increased expression of FSTL1 and its receptor DIP2A in tumor tissues has also been reported as a significant poor prognostic factor in various types of cancer, including gastric cancer (GC). However, the relationship between FSTL1/DIP2A levels, especially those in the peripheral circulation, and clinical outcomes in anti-PD1/PDL1 therapy remains to be elucidated in clinical practice. We collected peripheral blood collected from patients with advanced GC before and after nivolumab monotherapy, and analyzed for FSTL1 by ELISA, and for DIP2A+ cells by flow cytometry, followed by statistical analysis of association with patient prognosis. High FSTL1 levels at baseline were significantly associated with shorter progression-free survival (PFS) and overall survival (OS). Patients with high levels of DIP2A+ subsets in CD11b+ myeloid cells, CD3+ T cells, and CD56+ NK cells both before and after treatment showed significantly shorter PFS and OS as compared to patients with low levels. Combination of low baseline levels of both FSTL1 and DIP2A+ cells identified patients with long-term survival, known as durable responders. These data suggest that high baseline levels of both FSTL1 and DIP2A+ cells in peripheral blood are significant poor prognostic factors for nivolumab therapy for advanced GC. Targeting the FSTL1-DIP2A axis may be a promising strategy to improve clinical outcomes in GC as a biomarker to predict anti-PD1/PDL1 therapeutic efficacy more accurately.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00262-025-04239-1.

BackgroundColorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, with cases expected to rise 60% by 2030, especially in Asia. Metastatic CRC (mCRC) has a poor 5-year survival rate of 14%, posing a major treatment challenge. Tumors with DNA mismatch repair deficiency (dMMR) and a high level of microsatellite instability (MSI-H) respond well to immune checkpoint inhibitors (ICIs), shifting treatment strategies. This systematic review and meta-analysis evaluate Pembrolizumab (PEM), Nivolumab (NIV), and Nivolumab plus Ipilimumab (NIV + IPI) for their promising antitumor efficacy in MSI-H/dMMR mCRC.MethodsThis systematic review followed PRISMA guidelines and Cochrane Handbook standards, covering studies from 2014 to 2024 on advanced CRC patients treated with ICIs. A comprehensive search across eight databases was conducted by 12 independent reviewers. Extracted outcomes included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and objective response rate (ORR). To facilitate pooled analysis, data reported as median and interquartile range (IQR), or median, minimum, and maximum were converted to mean and standard deviation (SD) using combined formulas by Luo D et al. and Wan X et al. Risk of bias was assessed using the Cochrane RoB 2 tool. Meta-analyses were performed using random-effects models, with subgroup analyses by dosage. Publication bias and sensitivity analyses were conducted. All statistical analyses used RevMan version 5.4.ResultsA total of 13 eligible studies were analyzed, with sample sizes ranging from 11 to 307 and follow-up durations between 5.3 and 44.5 months. NIV + IPI showed the highest efficacy across all endpoints: ORR 0.54 [95% CI: 0.45–0.65, I² = 75%], OS 0.84 [95% CI: 0.81–0.88, I² = 0%], PFS 0.73 [95% CI: 0.68–0.78, I² = 0%], and DCR 0.82 [95% CI: 0.77–0.86, I² = 0%]. This combination outperformed NIV alone, which demonstrated ORR 0.36 [95% CI: 0.21–0.60, I² = 81%], OS 0.73 [95% CI: 0.62–0.86, I² = 54%], PFS 0.54 [95% CI: 0.43–0.68, I² = 34%], and DCR 0.70 [95% CI: 0.64–0.77, I² = 0%]. PEM showed lower efficacy with ORR 0.33 [95% CI: 0.23–0.49, I² = 94.6%], OS 0.59 [95% CI: 0.31–0.66, I² = 94%], PFS 0.45 [95% CI: 0.31–0.66, I² = 84%], and DCR 0.73 [95% CI: 0.47–1.12, I² = 94%]. PEM’s 200 mg dosage subgroup exhibited the best performance in its group with an ORR of 0.45 [95% CI: 0.38–0.52, I² = 0%]. Despite these findings, heterogeneity was notably high in PEM-related studies, highlighting variability in populations and study designs. Overall, NIV + IPI demonstrated superior and more consistent clinical outcomes.ConclusionsThis study highlights NIV + IPI as a promising combination for advanced CRC, showing superior efficacy, while PEM also demonstrated potential. However, high heterogeneity suggests the need for further research. Acknowledging its limitations, this study marks a pioneering effort in comparing short- and long-term effects of anti-CTLA-4 and anti-PD-1 therapies, paving the way for future advancements in CRC treatment.

Abstract A subset of meningiomas, including the majority of grade II/III and a proportion of grade I tumors, are refractory to repetitive resection and radiotherapy, and are frequently fatal. Reports of effective medical therapy are extremely rare. Literature suggests that immune checkpoint systems might have a role in aggressive meningiomas. A single-arm, phase 2 study was conducted to evaluate the efficacy and safety of nivolumab for meningiomas refractory to surgery and radiotherapy. Nivolumab (480 mg) was administered intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) determined by a central independent review committee. To avoid premature discontinuation of potentially effective immunotherapy, response was evaluated based on the iRANO (meningioma) criteria, which is based on the RANO (meningioma) criteria (Neuro Oncol 21:26-36, 2019) with the integration of the immune-related response criteria outlined previously (Lancet Oncol 16:e534-e542, 2015). Archival tumor specimens were obtained from all 29 cases. A total of 29 patients started the study therapy. Response assessment by the central review committee was performed for 28 patients: grade I in 5, grade II in 19, andgrade III in 4 by definition of WHO2016. The best overall response was PR in 1, SD in 13, and uPD/cPD in 14. The ORR was 3.6% and PFS-6 was 23.9%. Nivolumab was well tolerated. There was no case with mutations in the DNA mismatch repair genes. One patient who had multiple grade I meningiomas with biopsy-proven lung metastases showed sustained PR following initial radiological progression. The TMB of the tumor was 8.1/MB. Some specific gene sets were shown to be enriched in the PR case. Although nivolumab monotherapy failed to meet the prespecified primary endpoint, our study demonstrated that a subset of patients could benefit from the therapy and that immune-related response criteria are necessary to evaluate immunotherapy for meningiomas.

Molecular determinants of therapeutic response to nivolumab in Relapsed/Refractory PTCL: An integrated multiomic study of A phase II investigator-initiated trial

Efficacy and safety of nivolumab-based therapies in first-line and Relapsed/Refractory Hodgkin lymphoma

Immune checkpoint inhibitors (ICIs) have improved treatment outcomes for gastric cancer. However, immune-related adverse events (irAEs) pose a major challenge. This study aimed to identify predictive factors for irAE occurrence in patients with advanced or recurrent gastric cancer treated with nivolumab. We retrospectively analyzed information of 115 patients with advanced or recurrent gastric cancer treated with nivolumab monotherapy or in combination with chemotherapy. Patient characteristics and laboratory data, including complete blood counts, and clinical outcomes were analyzed. Optimal cutoffs for potential predictive factors were determined using ROC curve analysis. irAEs developed in 21 patients, with a median onset time of 124days after treatment initiation. Patients with an eosinophil proportion ≥ 4% showed higher irAE rates compared to those with < 4%. Multivariate analysis identified eosinophil proportion ≥ 4% (odds ratio 5.0) and neutrophil-to-lymphocyte ratio < 1.9 (odds ratio 4.6) as independent predictors of irAE occurrence. Patients with an elevated eosinophil proportion had higher levels throughout the treatment than those without irAEs at baseline, two months, and three months after treatment initiation. Patients with eosinophil proportions ≥ 4% demonstrated better overall survival and a tendency toward improved progression-free survival. Elevated eosinophil proportion before ICI treatment was a predictor of irAE occurrence and was associated with improved survival in patients with advanced or recurrent gastric cancer. This readily available clinical parameter may help identify patients more likely to benefit from ICI therapy, while enabling closer monitoring of potential irAEs.

Circadian rhythms modulate immune function and may influence the efficacy of immune checkpoint inhibitors (ICIs). In small-scale studies, morning administration of ICIs has improved outcomes in patients with non-small cell lung cancer (NSCLC). This multicenter retrospective study evaluated the association between ICI administration timing and clinical outcomes in patients with NSCLC treated with nivolumab. We retrospectively analyzed patients with metastatic NSCLC receiving ≥3 courses of nivolumab monotherapy as second- or later-line therapy at two institutions. Patients were stratified into morning (≥2 infusions before 11:00) and afternoon (≥2 infusions after 11:00) groups based on the timing of their first three administrations. Overall survival (OS), progression-free survival (PFS) and tumor response were analyzed according to timing group. Among the 257 patients, 51 (19.8%) received morning and 206 (80.2%) afternoon administration. Median OS was significantly longer in the morning group [21.3 vs. 13.8 months; hazard ratio (HR)=0.64, 95% confidence interval (CI)=0.45-0.92; p=0.015]. PFS favored morning administration (6.54 vs. 4.21 months; HR=0.77, 95%CI=0.55-1.06; p=0.11). Multivariate analysis showed a non-significant trend favoring morning administration for OS (HR=0.75, 95%CI=0.52-1.09; p=0.14). Morning nivolumab administration may be associated with improved OS in patients with NSCLC. Prospective studies are warranted to clarify the clinical relevance of infusion timing and its possible contribution to treatment outcomes.

Abstract Disclosure: L. Vako: None. S. Kalik: None. N.E. Cusano: None. Background: Nivolumab is a Programmed Cell Death-1 (PD-1) immune checkpoint inhibitor used in cancer treatment. Nivolumab has been shown to cause endocrine-related adverse events, most commonly hypothyroidism, hypophysitis and adrenal insufficiency. Presentations can vary from vague symptoms to severe illness. Case Presentation: A 67-year-old man with bladder urothelial carcinoma was treated with a combination of gemcitabine, cisplatin, and nivolumab followed by nivolumab monotherapy. Prior to arrival in the emergency department, he had two episodes of new-onset absence seizures followed by a period of unresponsiveness while at an outpatient oncology appointment. These episodes resolved within a few minutes. Outpatient evaluation that morning showed: serum Na 124 mmol/L [reference range (RR): 135-145 mmol/L], AM cortisol 2.48 ug/dL (RR: 6.02-18.4 ug/dL), ACTH 17.4 pg/mL (RR: 7.2-63.3 pg/mL), TSH 9.93 uIU/mL (RR: 0.27-4.20 uIU/mL], and free T4 0.8 ng/dL (RR: 0.9-1.8 ng/dL). These results suggested new secondary adrenal insufficiency (AI) and primary hypothyroidism. He was hemodynamically stable. Admission evaluation showed: serum Na 128 mmol/L, serum osmolarity 265 mosm/kg (RR: 280-301 mosm/kg), urine osmolarity 111 mosm/kg (RR: 300-900 mosm/kg). He had reported drinking more water recently. He received one dose of hydrocortisone 100 mg IV for suspected AI and was placed on fluid restriction for suspected polydipsia. After four days, laboratories showed: AM cortisol 7.05 ug/dL, ACTH 15.9 pg/mL, TSH 6.52 uIU/mL, and free T4 0.624 ng/dL. He tested negative for thyroglobulin and thyroid peroxidase antibodies. There was otherwise normal anterior pituitary function of all other axes. CT scan of the head did not show any metastasis or acute processes. He did not undergo MRI as his symptoms improved rapidly. Na improved with one dose of steroid and fluid restriction. No further episodes of seizure-like activity occurred in the hospital. Additional steroids were held until the cosyntropin stimulation test was performed, demonstrating a baseline cortisol of 1.3 ug/dL with ACTH 10.4 pg/mL, and after 60 minutes, a suboptimal cortisol level of 11.3 ug/dL, confirming suspected secondary AI. He was started on hydrocortisone 10 mg in AM and 5 mg in PM. He was also started on levothyroxine 25 mcg for primary hypothyroidism. Na levels remained normal at 141 mmol/L after 1 month and he remained normotensive and seizure-free. Conclusion: This case highlights seizure as a severe presenting symptom of hyponatremia caused by Nivolumab-induced secondary AI and hypothyroidism. It is important to recognize adverse endocrine events related to check point inhibitors and initiate appropriate therapy. Presentation: Sunday, July 13, 2025

We previously demonstrated that immune cells expressing α-synuclein (SNCA) are dramatically increased in peripheral blood of patients with gastric cancer (GC), but rarely in healthy donors, and that blocking SNCA is significantly effective even in anti-PD1-resistant mouse tumor models with increased SNCA+ cells. This suggests that the increased SNCA+ cells are involved in resistance to anti-PD1 therapy. However, the relationship between SNCA+ cell levels and anti-PD1/PDL1 therapeutic efficacy in GC remains to be determined in clinical settings. In the WJOG10417GTR study, peripheral blood cells collected from advanced GC patients before and one month after nivolumab monotherapy were analyzed for several SNCA+ cell populations by flow cytometry, and the relationship between the levels and patient prognosis was statistically analyzed. High levels of SNCA+ cells, particularly the myeloid subset, before and after treatment were significantly associated with shorter progression-free survival and overall survival. Patients with low SNCA+ cell levels survived for a long time without disease progression, indicating durable responders. These suggest that SNCA+ cells are significant poor prognostic factors in nivolumab therapy for advanced GC. Targeting SNCA may be a promising strategy to improve clinical outcomes in anti-PD1/PDL1 therapy for GC.

BackgroundWe previously demonstrated that interleukin-33 (IL33) plays a key role in treatment resistance through tumor polyploidization and the consequent immune dysfunction by recruiting and expanding various immunosuppressive cells that express its receptor ST2, and that anti-IL33 blockade therapy induces potent anti-tumor effect in mouse tumor models resistant to anti-PD1 therapy. These suggest that IL33 and ST2 are potentially promising targets that could contribute to anti-PD1/PDL1 therapy. Recently, an increasing number of clinical studies have shown a significant correlation between IL33 expression in tumor tissues and poor prognosis in patients with gastric cancer (GC). However, the clinical significance of targeting the IL33-ST2 axis in anti-PD1/PDL1 therapy for GC remains unclear.MethodsTumor tissues and peripheral blood were collected from patients with advanced GC before and after nivolumab monotherapy in the WJOG10417GTR study. Gene expression of il33 in tumor tissues, IL33 in plasma, and ST2+ cell subsets in four cell populations (IL17RB+GATA3+ ILC2s, CD117+FceRIa+ mast cells, CD11b+HLA-DR−PDL1+ MDSCs, and CD3+CD4+FOXP3+ Tregs) in peripheral blood cells were analyzed by RNA-sequencing, IHC, ELISA, or flow cytometry, and the relationship between their levels and patient prognosis was statistically analyzed.ResultsThe levels of tumor il33 gene expression and peripheral IL33 and ST2+ cells were higher in patients who showed progressive disease (PD) than in non-PD patients. High levels of tumor il33 gene expression at post-treatment, and high levels of peripheral ST2+ cells at both pre- and post-treatment were significantly associated with shorter progression-free survival and overall survival. Patients with low post-treatment levels of both tumor il33 and peripheral ST2+ cells, especially the mast cell subset, had long-term survival without PD, indicating durable responders.ConclusionsThese data suggest high IL33/ST2 levels are significant poor prognostic factors for nivolumab therapy for advanced GC. The IL33/ST2 axis may be useful as a biomarker for predicting and pre-selecting possible responders/nonresponders to anti-PD1/PDL1 therapy for GC, and hopefully as a druggable target for developing new drugs for treating GC. The IL33/ST2-targeting strategy will contribute to improving clinical outcomes in the treatment of GC.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-025-07145-3.

BackgroundThe relationship between eosinophilia and cancer development has recently been investigated. However, the role of eosinophils in tumor immunity, particularly in the context of immune checkpoint inhibitor (ICI) therapy, remains poorly understood.MethodsWe investigated the relationship between peripheral blood eosinophil and T-lymphocyte subsets and the clinical characteristics of patients undergoing anti-programmed cell death-1 (PD-1) monotherapy for non-small cell lung cancer (NSCLC). The study included 204 patients treated with nivolumab monotherapy, and clinical data and treatment responses were recorded. PBMCs were collected from 44 out of 204 patients before treatment to analyze T-lymphocyte subsets, focusing on their correlation with blood eosinophils.ResultsThe percentage of blood eosinophils before nivolumab treatment was positively correlated with the percentage of effector memory subsets in both CD4+ (r = 0.43, p = 0.0045) and CD8+ T cells (r = 0.35, p = 0.020). It was negatively correlated with the percentage of naïve subsets of CD4+ T cells and positively correlated with the percentage of inducible T cell co-stimulator cells among CD8+ T cells. Patients with higher eosinophil levels (≥1.7%) before nivolumab treatment exhibited significantly longer progression-free survival (log-rank p = 0.014) and overall survival (log-rank p = 0.001) than those with lower eosinophil levels. An early increase in the eosinophil count after treatment was also associated with a better response to nivolumab.ConclusionHigher blood eosinophil levels may indicate activated T-cell immunity and may be a promising biomarker for the efficacy of anti-PD-1 monotherapy in patients with NSCLC.

Nivolumab alone and in combination with ipilimumab demonstrated durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer in the phase 2 CheckMate 142 study. Here, we report exploratory biomarker analyses from CheckMate 142 evaluating associations between various tissue biomarkers and the efficacy of nivolumab monotherapy and nivolumab plus ipilimumab combination in these patients. Higher expression of inflammation-related gene expression signatures is associated with improved response per investigator assessment and survival benefit with nivolumab monotherapy. In contrast, higher tumor mutational burden, tumor indel burden, and degrees of microsatellite instability are associated with improved response per investigator assessment and survival benefit with nivolumab plus ipilimumab. While interpretation is limited by the exploratory nature of these analyses, they suggest that tumor antigenicity rather than baseline tumor inflammation might be important for the combinatorial efficacy. Validation of these findings in larger, randomized studies is necessary.

Safety profile of nivolumab-relatlimab in cancer patients: a living pharmacovigilance study of clinical trials and postmarketing data (version 1.0).

P101-4 Efficacy of nivolumab plus ipilimumab versus monotherapy against advanced melanoma: a systematic review