Nivolumab In Patients Research Articles

Phase II trial of ibrutinib and nivolumab in patients with relapsed CNS lymphomas.

Treatment options are limited for both relapsed/refractory primary and secondary central nervous system (CNS) lymphoma and the prognosis remains poor. Prior studies have shown the activity of Bruton tyrosine kinase (BTK) inhibitors and programmed death-1 targeted therapies in CNS lymphoma and studies suggested potential synergy. Therefore, we conducted a phase 2 trial combining ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma. Patients received ibrutinib 560mg oral daily with nivolumab 240mg IV every 14 days (28-days per cycle). Patients who were in partial or complete response after 6 cycles of treatment could continue therapy for up to 2 years unless progression or unacceptable toxicity. Eighteen patients were enrolled with the median age was 63 years (range 43-88). The median number of prior lines of therapy was 2 (range, 1-4), 55% had refractory disease, 17% had prior stem cell transplant, and 11% had prior CAR T-cell therapy. The best overall response rate was 78% and the best complete response rate was 50% (95% CI: 26-74%). The median PFS and OS was 6.5 months and 21.0 months, respectively and three patients continue to be in remission over two years. Treatment was generally well tolerated but two patients stopped treatment due to fatigue. Ibrutinib and nivolumab resulted in reasonable safety and clinical activity in patients with refractory/relapsed CNS lymphoma and warrants further investigation. NCT03770416.

Phase II study of cabozantinib and nivolumab in refractory metastatic microsatellite stable (MSS) colorectal cancer (CRC).

229 Background: Current data suggest that combining tyrosine kinase inhibitors with immune checkpoint inhibitors may be a promising treatment strategy in patients with metastatic MSS CRC. This prospective, open-label, single-arm, phase II study (NCT04963283) evaluated the efficacy of cabozantinib in combination with nivolumab in patients with metastatic refractory MSS CRC. Methods: Patients with metastatic/unresectable MSS CRC who were refractory to chemotherapy in the 3 rd line setting and beyond were eligible. Patients were treated with cabozantinib 40 mg orally daily and nivolumab 480 mg IV every 28 days. Tumor assessments were obtained every 8 weeks for the first 16 weeks, and then every 12 weeks thereafter. Response was assessed via RECIST v1.1. The primary endpoint was 16-week disease control rate (16-wk DCR); secondary endpoints were objective response rate (ORR), progression free survival (PFS), overall survival (OS), safety and tolerability, and correlative studies (to be presented at a future date). Results: Between June 2021 and January 2024, 49 pts were enrolled; 63% were male; median age 55 [50-64]. Median prior treatment regimens were 4 [2-14]. Most patients (84%) had not received prior trifluridine/tipiracil; only 1 patient had received prior regorafenib. The 16-wk DCR was 40% (19/47) (95% CI 0.264 – 0.557). The 16-wk ORR was 8.5% (4/47) (95% CI 0.024 – 0.204). mPFS was 3.4 months (95% CI 1.8-5.0) and mOS was 10.9 months (95% CI 4.7-13.8). Thirty nine percent of patients experienced a serious adverse event (SAE), with 4% Gr 1, 37% Gr 2, 35% Gr 3 and 4% Gr 4; there were no Gr 5 treatment related adverse events. The most common AEs were diarrhea (53%), fatigue (43%), hypothyroidism (31%), weight loss (29%), nausea (29%), and hypertension (27%). Two patients remain on study at time of abstract submission. Conclusions: The combination of cabozantinib and nivolumabwas well tolerated and provided modest benefit in a population of patients with metastatic, chemotherapy refractory, MSS CRC. Clinical trial information: NCT04963283 .

Nivolumab and hypofractionated radiotherapy in patients with advanced melanoma: A phase 2 trial.

Radiotherapy is thought to enhance anti-tumor immunity, particularly when delivered in a hypofractionated and multisite manner. Therefore, we investigated the effects of combining radiotherapy with nivolumab in patients with advanced melanoma. This was a multicenter, non-randomized, phase 2 trial that enrolled patients with treatment-naïve metastatic melanoma. They received nivolumab (240 mg / 2 weeks) plus radiotherapy (day 15, 6 Gy × 3). When feasible, one target from each organ was irradiated (no irradiation of all targets). The primary endpoint was 1-year overall survival (OS). This trial included 64 patients between March 2017 and July 2019. The median follow-up was 23.5 (2.3-43.8) months. The median age was 68 (35-95) years, patients were mostly male (67 %) with an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0 (72 %), stage IV-M1c disease (47 %), and were BRAF-wild-type (67 %). The 2-year OS and 1-year PFS rates were 65.2 % and 56 %, respectively (P = 0.22 and P = 0.03, vs. 58 % and 43 %, respectively, in the Checkmate 066 study). Thirty-seven (58 %) and twenty-seven (42 %) patients were irradiated at one and multiple targets, respectively. The ECOG-PS (1 vs. 0; HR = 3.5; P = 0.005) was an independent prognostic factor for OS. Irradiating more than one site and irradiating a smaller cumulative tumor volume tended to correlate with better outcome. Grade 3-4 treatment-related adverse events occurred in 21.9 % of the patients (no grade 5). Combined immunotherapy and hypofractionated radiotherapy did not improve survival compared to historical cohorts. The radiotherapy schedule needs to be optimized in order to improve these results.

Analysis of Pleiotropic Effects of Nivolumab in Patients with Relapsed Pleural Mesothelioma: A Single-Center Retrospective Study

Plain Language SummaryPleural mesothelioma is a rare and aggressive cancer affecting the lining of the lungs. Treatment options are limited, especially for patients whose disease has worsened after initial therapies. Nivolumab, an immune checkpoint inhibitor, was approved in Japan in 2018 to treat patients with pleural mesothelioma who had already received other treatments. This study looked at 83 patients with pleural mesothelioma who were treated with nivolumab between 2018 and 2022 at a single medical center. We wanted to see how effective and safe nivolumab was in real-world clinical practice. Our study found that 16 patients had a partial reduction in their cancer, while 30 patients’ disease remained stable. However, in 29 patients, the disease progressed. Overall, 19.3% of patients responded to the treatment, and the disease was controlled in 55.4% of patients. The median time before the disease worsened again (progression-free survival) was 5.1 months, and the median overall survival was 12.4 months. Side effects related to the treatment occurred in just over half of the patients, with 7.2% experiencing severe side effects, including one death. Our findings suggest that nivolumab is a helpful treatment for pleural mesothelioma patients who have a good performance status, meaning they are still able to carry out daily activities despite their illness. The study supports using nivolumab in patients even after other treatments have failed, but more research is needed to confirm these results.

Next generation sequencing-based MSI scoring predict benefit in mismatch repair deficient tumors treated with nivolumab: follow-up on NCI-MATCH arm Z1D.

Mismatch repair deficient (dMMR) tumors have demonstrated favorable responses to immune checkpoint inhibition targeting PD-1. However, more in-depth identification of predictors of response could further refine patient selection for immunotherapy treatment. We undertook integrated evaluation performed on samples collected from 28 of 42 patients enrolled on the NCI-MATCH arm Z1D trial that evaluated PD-1 inhibition treatment with nivolumab in patients with non-colorectal dMMR tumors. Genomic analyses were performed using next-generation sequencing (NGS), whole exome sequencing, and RNA sequencing and supplemented by multiplex immunofluorescence performed on tissue samples. In this dMMR population, more extensive alterations of microsatellites as assessed by measures of NGS was associated with clinical benefit and tumor mutational burden. RNA sequencing further revealed associations between clinical benefit and immune infiltration index. Gene sets enriched in patients with clinical benefit included interferon signaling, antigen processing and PI3K-AKT-mTOR signaling, while hedgehog signaling was found to be enriched in subjects lacking clinical benefit. These genomic data highlight the importance of immune infiltration and antigen presentation in dMMR tumors that respond to immune checkpoint blockade. In addition, they suggest that, even within a dMMR population, NGS based measures of MSI could serve as biomarkers of immunotherapy response.

Three-Year Overall Survival With Nivolumab Plus Relatlimab in Advanced Melanoma From RELATIVITY-047.

Nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), along with a clinically meaningful, but not statistically significant improvement in overall survival (OS) and a numerically higher objective response rate (ORR) compared with nivolumab in the RELATIVITY-047 trial (ClinicalTrials.gov identifier: NCT03470922). We report updated descriptive efficacy and safety results from RELATIVITY-047 with a median follow-up of 33.8 months. Median PFS was 10.2 months (95% CI, 6.5 to 15.4) with nivolumab plus relatlimab and 4.6 months (95% CI, 3.5 to 6.5) with nivolumab (hazard ratio [HR], 0.79 [95% CI, 0.66 to 0.95]); median OS was 51.0 months (95% CI, 34.0 to not reached) and 34.1 (95% CI, 25.2 to 44.7) months, respectively (HR, 0.80 [95% CI, 0.66 to 0.99]). ORR was 43.7% (95% CI, 38.4 to 49.0) with nivolumab plus relatlimab and 33.7% (95% CI, 28.8 to 38.9) with nivolumab. Efficacy across the majority of prespecified subgroups favored the combination. No new or unexpected safety signals were identified. Overall, at 3-year follow-up, the benefit observed with nivolumab plus relatlimab compared with nivolumab in patients with advanced melanoma was sustained, with the OS HR 95% CI upper bound now <1. This benefit is accompanied by a safety profile consistent with previous reports.

High peripheral T cell diversity is associated with lower risk of toxicity and superior response to dual immune checkpoint inhibitor therapy in patients with metastatic NSCLC

IntroductionDespite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable....

EE36 Cost-Effectiveness of Adjuvant Nivolumab in Patients With Stage II/III Carcinoma of the Esophagus or Gastroesophageal Junction and Residual Disease After Neoadjuvant Chemo-Radiotherapy Following Complete Resection in Austria

EE36 Cost-Effectiveness of Adjuvant Nivolumab in Patients With Stage II/III Carcinoma of the Esophagus or Gastroesophageal Junction and Residual Disease After Neoadjuvant Chemo-Radiotherapy Following Complete Resection in Austria

Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma.

Nivolumab (NIVO) + ipilimumab (IPI) combination and NIVO monotherapy have demonstrated durable clinical benefit in patients with unresectable/metastatic melanoma. This analysis describes long-term overall survival (OS) with the combination or monotherapy pooled across all major company-sponsored trials, as well as clinical factors associated with survival, in patients with immune checkpoint inhibitor (ICI) treatment-naïve unresectable/metastatic melanoma. Data were pooled from six CheckMate studies in ICI treatment-naïve patients receiving NIVO + IPI (NIVO 1 mg/kg + IPI 3 mg/kg or NIVO 3 mg/kg + IPI 1 mg/kg) or NIVO monotherapy (3 mg/kg). OS was assessed for each treatment, as well as in select subgroups. Cox proportional multivariate analysis (MVA) and classification and regression tree (CART) analyses were performed within treatment arms. Median follow-up for OS was 45.0 months for patients treated with NIVO + IPI (n = 839) and 35.8 months for patients treated with NIVO (n = 536). OS was longer with NIVO + IPI versus NIVO monotherapy (hazard ratio, 0.78 [95% CI, 0.67 to 0.91]), with 6-year OS rates of 52% versus 41%, respectively. Consistent benefit was observed in BRAF-mutant and BRAF-wild-type patients and those with normal and elevated lactate dehydrogenase (LDH). Numerical difference in OS was also observed across PD-L1 expression levels, although more pronounced with no/low PD-L1 expression. Clinical factors associated with decreased survival in both the MVA and CART analyses were LDH > upper limit of normal with either treatment, age ≥65 years with NIVO + IPI, and the presence of liver metastases with NIVO monotherapy. In this large, pooled nonrandomized retrospective analysis, we observed that NIVO + IPI provides longer OS than NIVO in patients with ICI treatment-naïve advanced melanoma and identifies clinical factors that appear to be associated with survival for each treatment, which may assist with treatment decision making.

Phase II trial of multi-tyrosine kinase inhibitor ESK981 in combination with PD-1 inhibitor nivolumab in patients with metastatic castration-resistant prostate cancer.

Increasing the response rates of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) presents a significant challenge. ESK981 is a multi-tyrosine kinase and PIKfyve lipid kinase inhibitor that augments immunotherapeutic responses. In this phase II study, ESK981 was combined with the PD-1 blocking monoclonal antibody nivolumab to test for potentially improved response rates in patients with mCRPC who have progressed on androgen receptor (AR)-targeted agents and chemotherapy. Eligible patients received ESK981 orally once daily for five consecutive days, followed by a two-day break. Patients were also treated with nivolumab intravenously on Day 1 of each 28-day cycle. The primary endpoints were a 50% reduction in prostate-specific antigen (PSA50), and safety. Secondary endpoints included radiographic progression free survival (rPFS) and overall survival (OS). Additional investigations included whole exome sequencing in patients. Ten patients were enrolled. The maximum PSA decline from baseline of 14% was achieved in only one patient. Grade 3 treatment-related adverse events (AEs) included fatigue, anemia, and lymphopenia. There were no Grade 4 events. The median rPFS was 3.7 months (95% CI, 1.6-8.4). The median OS was 9.6 months (95% CI, 1.8-22.4). The study was terminated due to futility after 10 patients. Whole exome sequencing identified AR amplification in 63% of patients (5/8). ESK981 + nivolumab showed no antitumor activity in patients with AR-positive (AR+) mCRPC. Further evaluation of ESK981 combined with the PD-1 inhibitor nivolumab in AR + mCRPC patients is not warranted. (Trial registration: ClinicalTrials.gov NCT04159896. Registration date: November 12, 2019.).

Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Results of Polish multicenter observational study.

Patients with head and neck squamous cell carcinoma (HNSCC) who have progressed following primary treatment (PT) have a poor prognosis. In this group, nivolumab has been demonstrated to significantly improve outcomes. This study presents the efficacy of nivolumab in Polish patients with recurrent and/or metastatic (R/M) HNSCC using real-world data. The analyzed group consisted of 324 adult patients with R/M HNSCC following platinum-based therapy. Patients were divided into 3 groups based on the time from completion of PT to nivolumab initiation (tPT-N): within 6 months (refractory), between 6 and 24 months (sensitive, tPT-N ≤24), and beyond 24 months (sensitive, tPT-N >24). Survival analysis and the Cox proportional hazards model were performed to evaluate how various risk factors affect patient outcomes. The 1-year and 2-year overall survival (OS) was 19.1%, 6.1%, 30.7%, 9.4%, and 45.7%, 29.1% in refractory, sensitive tPT-N ≤24, sensitive tPT-N >24 patients, respectively and was higher for both sensitivity groups vs. refractory (p = .004) and for sensitive tPT-N >24 versus refractory and sensitive tPT-N ≤24 (p <.001). Patients with nasopharyngeal cancer had OS significantly higher than patients with other primary tumor localization. The multivariate Cox analysis showed a significant favorable effect of tPT-N >24 (HR = 0.53, p = .001) and nasopharyngeal cancer on OS (HR = 0.20, p = .008). Conversely, female sex was identified as an unfavorable factor for OS (HR = 1.48, p = .020). In our study, we established that the benefit of nivolumab increases with the increasing tPT-N. The probability of death is significantly lower in male patients and patients with nasopharyngeal cancer regardless of tPT-N.

Ipilimumab with and without Nivolumab in Patients with Classic Hodgkin Lymphoma with Progression after PD-1 Blockade

Ipilimumab with and without Nivolumab in Patients with Classic Hodgkin Lymphoma with Progression after PD-1 Blockade

Nivolumab in Patients With Advanced or Metastatic Malignancies, Including Rare Cancers: Results of CheckMate 627, an Adaptive Basket Design Clinical Trial

PURPOSE To report on CheckMate 627 (ClinicalTrials.gov identifier: NCT02832167 ), a phase II adaptive basket design trial of nivolumab in uncommon advanced/metastatic tumors. METHODS Adults with previously treated advanced/metastatic malignancies received nivolumab 240 mg once every 2 weeks for eight cycles, followed by nivolumab 480 mg once every 4 weeks. The primary end point was investigator-assessed objective response rate (ORR). In addition to observed ORRs, model-adjusted ORRs were estimated via Bayesian analysis in patients who completed ≥28 weeks of follow-up, to correct for variability inherent in multitumor studies. This adaptive model allowed for borrowing of information from other tumors demonstrating similar ORR and evaluation of nivolumab treatment effect versus historical standard-of-care (SOC) controls. Nivolumab was considered to have met the criteria for ORR superiority in a group if there was ≥80% posterior probability of ORR with nivolumab exceeding ORR with historical SOC control treatment in that group. RESULTS The study included 25 tumor groups (n = 239), with 24 groups included in the Bayesian ORR analysis (efficacy was reported but not modeled in the other group that contained a mix of tumor types). The poorly differentiated neuroendocrine tumor (PD-NET) group (n = 20) met the prespecified criterion for ORR superiority with a 93% probability of the model-adjusted ORR with nivolumab (22% [95% CI, 8 to 44]) exceeding the respective historical SOC ORR of 10.0%. The observed ORR was 30.0% (95% CI, 11.9 to 54.3). There were no new safety signals for nivolumab. CONCLUSION Nivolumab showed evidence of antitumor activity in patients with advanced/metastatic PD-NET in CheckMate 627. The results of this study support the use of an adaptive basket design for identification of rare cancers responsive to immunotherapy.

Stereotactic Radiotherapy Plus Nivolumab in Patients with Locally Advanced Pancreatic Cancer: Results from Phase 1/2 Clinical CA209-9KH Trial.

The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) highlights the urgent need for novel therapeutic strategies. Immune checkpoint inhibitors (ICIs) seem to be ineffective in most PDAC studies. Therefore, we conducted an open-label, multicenter phase 1/2 study (CA209-9KH) to evaluate the safety of stereotactic radiotherapy (SRT) and sequential ICI therapy in PDAC, as well as to validate the efficacy of this regimen as a potential activator of antitumor immunity. Patients aged ≥ 18years with unresectable non-metastatic PDAC following four FOLFIRINOX induction cycles were included. Treatment comprised SRT (4 × 8Gy) and sequential nivolumab administration until disease progression or unacceptable toxicity. The primary endpoints were safety and toxicity assessment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), biomarker evaluation, and quality of life (QoL) analysis. Twenty-two patients were screened, with 15 enrolled. Eleven (median) nivolumab cycles were administered. SRT demonstrated low and clinically nonsignificant toxicity, whereas nivolumab toxicity aligned with prior safety profiles, without grade 4-5 events observed. Three patients discontinued therapy owing to toxicity. Median PFS and OS were 8.1 and 13.0months, respectively, with 12-month PFS and OS rates of 0% and 66.7%, respectively, and a 24-month OS rate of 8.9%. Biomarker levels correlated with clinical or radiological disease control. Patient-reported QoL remained acceptable, deteriorating with disease progression. SRT and nivolumab therapy exhibited manageable toxicity profiles consistent with previous findings; however, long-term treatment responses were not achieved with this regimen in locally advanced PDAC. Another strategy to trigger antitumor immunity in PDAC needs to be sought. EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432.

Neoadjuvant Intratumoral Plasmid IL-12 Electro-Gene-Transfer and Nivolumab in Patients with Operable, Locoregionally Advanced Melanoma.

Intratumoral tavokinogene telseplasmid delivered by electroporation (TAVO-EP) results in localized expression of IL-12 within the tumor microenvironment (TME). This study evaluated neoadjuvant TAVO-EP combined with intravenous nivolumab followed by surgery and adjuvant nivolumab in patients with operable, locoregionally advanced melanoma. The neoadjuvant phase comprised up to 3 × 4-week cycles during which TAVO-EP was given intratumorally on days 1, 8, and 15 (optional) concurrently with 480 mg nivolumab intravenously on day 8 of each 4-week cycle. Surgery followed, and adjuvant nivolumab was initiated after surgery. The primary endpoint was pathologic complete response (pCR). Secondary endpoints included major pathologic response (MPR; pCR or near pCR). Sixteen patients were enrolled, and the preoperative radiological response rate was 63%. One patient declined surgery after experiencing a significant clinical response. Among the remaining 15 patients, the pCR rate was 60% and the MPR was 80%. No patient with MPR has had disease recurrence with a median follow-up from the date of surgery of 15.4 months. At baseline, most patients exhibited low CD8+ tumor-infiltrating lymphocytes, PD-L1, and IFN-γ gene expression signature. There was enhanced immune activation following treatment in the TME and blood, including increased immune-related gene expression, CD8+ tumor-infiltrating lymphocytes, and proliferating immune cell subsets. The clinical efficacy of neoadjuvant intratumoral TAVO-EP + nivolumab is promising with 80% of patients achieving an MPR. Evidence of potent immune activation both systemically and within the TME along with a favorable safety profile supports the activity of local IL-12 and anti-PD-1 based regimens.

Trastuzumab Deruxtecan with Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study.

This multicenter phase Ib study investigated trastuzumab deruxtecan (T-DXd) plus nivolumab in patients with HER2-expressing metastatic breast cancer (mBC) and metastatic urothelial cancer (mUC). Part 1 determined the recommended dose for expansion of T-DXd plus nivolumab. Part 2 evaluated efficacy and safety; the primary endpoint was confirmed objective response rate by independent central review. In part 1, seven patients with mBC were enrolled and received T-DXd 3.2 mg/kg (four patients) or 5.4 mg/kg (three patients) plus nivolumab. The recommended dose for expansion for T-DXd was 5.4 mg/kg plus nivolumab 360 mg intravenously every 3 weeks. In part 2, 32 patients with HER2-positive mBC (cohort 1; inclusive of three administered 5.4 mg/kg in part 1), 16 with HER2-low mBC (cohort 2), 30 with HER2-high mUC (cohort 3), and four with HER2-low mUC (cohort 4) were enrolled. At data cutoff (July 22, 2021), the confirmed objective response rates (95% confidence interval) for cohorts 1 to 4 were 65.6% (46.8%-81.4%), 50.0% (24.7%-75.3%), 36.7% (19.9%-56.1%), and not assessed due to small sample size, respectively. The median treatment duration (range) with T-DXd in cohorts 1 to 4 was 8.9 (1-23) months, 6.9 (1-21) months, 3.9 (1-21) months, and not assessed, respectively; the most common treatment-emergent adverse event was nausea (55.2%, 62.5%, 73.3%, and 75.0%, respectively). Adjudicated drug-related interstitial lung disease/pneumonitis rates (cohorts 1-3) were 20.7%, 0%, and 20.0%, respectively (one grade 5 each, cohorts 1 and 3). T-DXd plus nivolumab demonstrated promising antitumor activity in HER2-expressing mBC or mUC and safety consistent with the known profile of T-DXd. Interstitial lung disease/pneumonitis is an important risk and requires careful monitoring and prompt intervention.

P4.14C.02 Analysis of Pleiotropic Effects of Nivolumab in Patients with Relapsed Pleural Mesothelioma: A Single Center Retrospective Study

P4.14C.02 Analysis of Pleiotropic Effects of Nivolumab in Patients with Relapsed Pleural Mesothelioma: A Single Center Retrospective Study

Efficacy of timing‑dependent infusion of nivolumab in patients with advanced gastric cancer.

Although an association exists between the timing of immune checkpoint inhibitor (ICI) administration and therapeutic efficacy in several types of cancer, to the best of our knowledge, no reports exist regarding this relationship in gastric cancer (GC). The present study aimed to evaluate the optimal timing of ICI (nivolumab) administration in patients with advanced GC. A total of 58 consecutive patients with advanced GC who received nivolumab monotherapy after ≥2 chemotherapy regimens were retrospectively evaluated. These patients were divided into two groups according to the median time of nivolumab administration: i) Early-timing and (ii) late-timing groups, and the efficacy was assessed in both groups. The early-timing group had significantly longer overall survival (OS) than the late-timing group [median OS 8.2 months; 95% confidence interval (CI), 4.2-12.9 vs. median OS 5.4 months; 95% CI, 3.6-6.1]. Moreover, patients in the early-timing group had significantly longer progression-free survival (PFS) than those in the late-timing group (median PFS 2.6 months; 95% CI, 1.3-3.9 months vs. median PFS 1.6 months; 95% CI, 0.9-2.1 months). Furthermore, univariate analysis showed that early timing, immune-related adverse events and nonsteroidal anti-inflammatory drug administration were associated with longer OS and PFS. Cutoff Finder analysis revealed that the optimal timing of nivolumab administration for achieving better outcomes was before 12:06 p.m. Nivolumab administration in the morning, especially before 12:06 p.m., had a better clinical impact on patients with advanced GC.

Nivolumab in Patients with Metastatic Castration-Resistant Prostate Cancer with and without DNA Repair Defects.

Despite the success of immune checkpoint inhibitors (ICI) across various cancers, their efficacy in metastatic castration-resistant prostate cancer (mCRPC) is modest, except for a subset of patients who experience significant, yet unpredictable, benefits. DNA repair defects (DRD) are associated with higher neoantigen load, which may predict response. Our study explored the potential of DRD for enhanced responsiveness to the ICI nivolumab. We conducted a phase II, multicenter, single-arm trial evaluating nivolumab in patients with mCRPC with prior docetaxel therapy. The DRD were assessed using ctDNA. The primary endpoint was PSA50 response. Secondary endpoints included the objective response rate, radiographic progression-free survival (rPFS), and overall survival. Also, exploratory comprehensive genomic profiling was performed via whole-exome sequencing of tumor samples and matched normal tissues, alongside PD-L1 expression evaluation. Among the 38 enrolled patients, DRD was identifiable in 30.5% (11/36) through ctDNA and/or whole-exome sequencing analyses. The overall PSA50 response rate was 10.5% (4/38). The PSA50 and objective response rates did not significantly differ between patients with and without DRD (18.2% vs. 8%; P = 0.57 and 50% vs. 17.6%; P = 0.27, respectively). The median PSA-PFS (1.9 vs. 2.8 months; P = 0.52) and rPFS (3.4 vs. 5.5 months; P = 0.7) were not statistically different between patients with and without DRD. Grade ≥ 3 adverse events were reported in 47.3% of participants. Nivolumab has clinical activity in a subset of patients with mCRPC; however, DRD does not predict response. These results highlight the necessity of identifying new biomarkers to more accurately determine patients with mCRPC who might respond to ICIs.

Real-world safety of nivolumab in patients with malignant pleural mesothelioma in Japan: post-marketing surveillance study.

This post-marketing surveillance (PMS) was conducted to evaluate the incidence of adverse events with nivolumab in patients with unresectable, advanced or recurrent malignant pleural mesothelioma (MPM) that had progressed after first-line chemotherapy and to identify factors that potentially affected its safety in real-world clinical practice. Patients who had not received nivolumab previously were registered between November 2018 and February 2021. Nivolumab was given intravenously 240mg every 2weeks or 480mg every 4weeks. Patients were followed up for 6months after treatment initiation. Information on patient characteristics, treatment status, and adverse events was collected. This PMS enrolled 124 patients, involving 48 sites across Japan. At 6months, nivolumab therapy was ongoing in 35.5% of patients (44/124) and had been discontinued in 64.5% (80/124). The overall incidence of treatment-related adverse events (TRAEs) was 40.3%; the incidence of Grade 3 or higher TRAEs was 12.9%. The pattern of TRAEs based on System Organ Class categories was generally consistent with those seen in the Japanese phase II MERIT study. The most common Grade 3 or higher TRAEs were interstitial lung disease (2.4%), lung disorder, and diarrhea (each 1.6%). The incidence of TRAEs was significantly higher in inpatients or patients who had good PS, high bodyweight, high body mass index, or autoimmune diseases than in those without these characteristics. The post-marketing incidence of TRAEs with nivolumab in patients with MPM has been evaluated, and no new safety signals were identified compared to the phase II clinical trial in Japan.