Nivolumab Research Articles

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.

P181 WITNESS: Real-world outcomes of Nivolumab (NIVO) + Ipilimumab (IPI) in patients (pts) with previously untreated clear cell advanced Renal Cell Carcinoma (aRCC) in France - 1 year minimum follow-up

P181 WITNESS: Real-world outcomes of Nivolumab (NIVO) + Ipilimumab (IPI) in patients (pts) with previously untreated clear cell advanced Renal Cell Carcinoma (aRCC) in France - 1 year minimum follow-up

P177 WITNESS : Real-world outcomes of nivolumab (NIVO) in patients (pts) with previously treated advanced renal cell carcinoma (aRCC) in France - final analysis and outcomes in elderly patients

P177 WITNESS : Real-world outcomes of nivolumab (NIVO) in patients (pts) with previously treated advanced renal cell carcinoma (aRCC) in France - final analysis and outcomes in elderly patients

Prospective screening and proposed treatment algorithm for immune checkpoint inhibitor induced myositis in neoadjuvant-treated rectal cancer patients: data from the phase II CHINOREC trial

Abstract Background Myositis is an infrequent (<1%) but potentially life-threatening (case fatality rate 40-50%) immune-related adverse event (irAEs) of immune checkpoint inhibitors (ICI), such as ipilimumab (IPI) and nivolumab (NIVO). The true incidence is likely to be underestimated and may not be representative for curative neoadjuvant treatment approaches in gastrointestinal (GI) cancers, especially in combination with chemoradiotherapy (CRT). Currently, the summary of product characteristics (SmPC) does not suggest any pre-emptive screening or surveillance. Methods The CHINOREC study is an ongoing prospective, randomized, open-label, multicenter, phase II investigator-initiated trial (IIT). Patients with intermediate to locally advanced rectal cancer (LARC) receive either neoadjuvant CRT alone or in combination with a single dose of IPI and 3 cycles of NIVO, following surgical resection. Patients are monitored at baseline and throughout the whole study period for myotoxicity biomarkers, including cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Findings From 06/2020 to 11/2023, 80 patients have been enrolled of whom 50 patients were randomized to the CRT+IPI/NIVO arm. Six patients (12%) developed biopsy-verified myositis. Myositis treatment was promptly implemented using a pragmatic step-up approach. Patients received glucocorticoids (GC) with concomitant intravenous immunoglobulin (IVIG). If myotoxicity biomarkers did not improve, patients received infliximab (INFLIXI) and/or plasma exchange (PLEX). Although all patients had strikingly elevated cTnT (median peak 284 ng/L, 95% CI 39-3097), cTnI levels remained largely normal, correlating with a negative cardiac magnetic resonance (CMR). All patients underwent successful tumor surgery without any major surgical complication. As of today, all patients' creatine kinase (CK) and myoglobin (MB) levels have normalized and they are tumor free without any major sequela. Interpretation Longitudinal biomarker screening (cTnT/cTnI) for ICI-induced myotoxicities is pivotal in curative neoadjuvant-treated cancer patients to initiate an early counter treatment in a holistic step-up approach, without compromising oncological principles.

Intracranial administration of anti-PD-1 and anti-CTLA-4 immune checkpoint-blocking monoclonal antibodies in patients with recurrent high-grade glioma.

Recurrent high-grade glioma (rHGG) lacks effective life-prolonging treatments and the efficacy of systemic PD-1 and CTLA-4 immune checkpoint inhibitors is limited. The multi-cohort Glitipni phase I trial investigates the safety and feasibility of intraoperative intracerebral (iCer) and postoperative intracavitary (iCav) nivolumab (NIVO) ± ipilimumab (IPI) treatment following maximal safe resection (MSR) in rHGG. Patients received 10mg IV NIVO within 24h before surgery, followed by MSR, iCer 5mg IPI and 10mg NIVO, and Ommaya catheter placement in the resection cavity. Biweekly postoperative iCav administrations of 1-5-10mg NIVO (cohort 4) or 10mg NIVO plus 1-5-10mg IPI (cohort 7) were combined with 10mg IV NIVO for 11 cycles. 42 rHGG patients underwent MSR with iCer NIVO + IPI. 16 pts were treated in cohort 4 (postoperative iCav NIVO at escalating doses) while 28 patients were treated in cohort 7 (intra and postoperative iCav NIVO and escalating doses of IPI). The most common TRAE was fatigue; no grade 5 AE occurred. Dose-limiting toxicity was grade 3 neutrophilic pleocytosis (4 pts) receiving iCav NIVO plus 5 or 10mg IPI. PFS and OS did not significantly differ between cohorts (median OS: 42 [95% CI 26-57] vs. 35 [29-40] weeks; 1-year OS rate: 37% vs. 29%). Baseline B7-H3 expression significantly correlated with worse survival. OS compared favorably to a historical pooled cohort (n = 469) of Belgian rHGG pts treated with anti-VEGF therapies (log-rank P = .015). Intraoperative iCer IPI + NIVO with postoperative iCav NIVO±IPI up to biweekly doses of 1mg IPI + 10mg NIVO is feasible and safe, showing encouraging OS in rHGG patients. ClinicalTrials.gov registration: NCT03233152.

Estimating Long-Term Survivorship Rates Among Patients With Resected Stage III/IV Melanoma: Analyses From CheckMate 238 and European Organization for Research and Treatment of Cancer 18071 Trials.

Standard-of-care treatments for patients with resected stage III/IV melanoma include the immuno-oncology (IO) agents nivolumab (NIVO) and ipilimumab (IPI). This study used mixture cure models (MCMs) to estimate cure rates among patients treated with NIVO or IPI in the phase III CheckMate 238 (ClinicalTrials.gov identifier: NCT02388906) and European Organization for Research and Treatment of Cancer (EORTC) 18071 (ClinicalTrials.gov identifier: NCT00636168) trials, and to assess the impact of use of adjuvant immunotherapy on cure rates versus watchful waiting. MCMs were applied to patient-level recurrence-free survival data from CheckMate 238 and EORTC 18071. Cured patients were assumed to experience no disease recurrence and mortality risks similar to the general population. Uncured patients were at risk of disease recurrence and all-cause death. The survival trend of the cured patients was estimated using life expectancy data for a general population with the same baseline demographic characteristics. A regression model assessed the odds ratios (ORs) of cure across key subgroups on the basis of baseline characteristics of the study populations. In CheckMate 238, estimated cure rates were 48.3% (95% CI, 41.8 to 54.9) with NIVO and 38.2% (95% CI, 32.7 to 44.1) with IPI. In EORTC 18071, estimated cure rates were 38.0% (95% CI, 32.1 to 44.2) with IPI and 29.2% (95% CI, 24.4 to 34.6) with placebo. In the indirect comparison of the two trials, the odds of cure were significantly higher with NIVO than with placebo (OR, 2.33 [95% CI, 1.49 to 3.65]). Analyses involving two large phase III trials investigating adjuvant IO treatment for resected melanoma demonstrate higher cure rates for both NIVO and IPI than placebo, with NIVO providing the highest cure rate. Similar cure rates were estimated for patients treated with IPI in both trials, despite staging and dosing differences.

Bempegaldesleukin plus nivolumab in first-line advanced/metastatic urothelial carcinoma: Results from a phase II single-arm study (PIVOT-10)

BackgroundIn PIVOT-02, bempegaldesleukin (BEMPEG), a pegylated interleukin-2 cytokine prodrug, in combination with nivolumab (NIVO), a Programmed cell death protein 1 inhibitor, demonstrated the potential to provide additional benefits over immune checkpoint inhibitor monotherapy in patients with urothelial carcinoma, warranting further investigation. We evaluated BEMPEG plus NIVO in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial carcinoma. MethodsThis open-label, multicenter, single-arm, phase II study enrolled patients with locally advanced/surgically unresectable or metastatic urothelial carcinoma and who were ineligible for cisplatin-based treatment. Patients received BEMPEG plus NIVO were administered intravenously every 3 weeks for ≤2 years or until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review (BICR) in patients with low programmed death ligand-1 (PD-L1) expression. Secondary endpoints included ORR and duration of response in the overall population. Progression-free survival (PFS) and overall survival (OS) were exploratory endpoints. ResultsOne hundred and eighty-eight patients were enrolled; 123 patients were PD-L1 low (combined positive score [CPS] <10; 65.4%), 59 were PD-L1 high (31.4%; CPS ≥10), and 6 had PD-L1 status unknown (3.2%). ORR per blinded independent central review in patients with PD-L1-low tumors was 17.9% (95% confidence interval [CI] 11.6–25.8) while in all treated patients was 19.7% (95% CI 14.3–26.1). Median PFS and OS in the overall population were 3.0 months and 12.6 months, respectively. BEMPEG plus NIVO combination was well tolerated, with a safety profile similar to previously reported trials; no new or unexpected safety signals were reported. ConclusionsBEMPEG plus NIVO did not meet the efficacy threshold for ORR in patients with previously untreated locally advanced or metastatic urothelial carcinoma and low PD-L1 expression.

Synthesis and Evaluation of amyloid beta peptide/ Ruthenium III -based complex drugs as drug delivery and anticancer activity

The development and characterization of anticancer complex drugs (ACD), specifically Amyloid Beta Peptide (ABP) - Ruthenium III (Ru III) - nivolumab (NB), were explored through analytical techniques. Fourier-transform infrared (FTIR) spectroscopy demonstrated the structural transformation of peptides from α-helical to β-sheet formations, aligning with amyloid fibril aggregation. Ruthenium (III) complex synthesis was confirmed through distinct absorption peaks in FTIR analysis. High-resolution scanning electron microscopy (HRSEM) revealed the fibrous and smooth morphology of ACD, while thermogravimetric analysis (TGA) confirmed the decomposition stages and stability of the ruthenium complexes. The encapsulation efficiency and in vitro release profile of nivolumab (NB) within ABP-RuIII-NB were investigated, showing a two-phase release over 40h. Cytotoxicity studies using acridine orange and ethidium bromide staining techniques indicated significant apoptosis in human oral squamous cell carcinoma (OSCC) -treated cells. These findings highlight the potential of ABP-RuIII-NB as an effective cancer treatment with controlled drug release and high cytotoxicity against cancer cells.

Real-world treatment patterns and outcomes of patients with advanced melanoma treated with nivolumab plus relatlimab

Abstract The use of programmed death-1 (PD-1) inhibitors has been a pivotal advancement in treating advanced melanoma, yet their efficacy is limited. The approval of relatlimab (RELA), a lymphocyte activation gene 3 protein (LAG-3) antibody, in combination with nivolumab (NIVO), a PD-1 inhibitor, marked a significant stride toward enhancing treatment efficacy for metastatic and unresectable stage 3 and 4 melanoma. This combination has been shown to synergistically improve antitumor activity and effector T-cell activity in the tumor microenvironment, despite limited data on real-world outcomes. Our retrospective review at a tertiary cancer center of patients with stage 3 and 4 melanoma treated with NIVO-RELA revealed an overall response rate (ORR) of 39%, with notable improvements in median PFS and ORR, especially in first-line treated patients. Our study highlights the superior efficacy of NIVO-RELA over previous reports, demonstrating its significant potential in the treatment landscape of advanced melanoma.

LBA53 Nivolumab (NIVO) plus relatlimab with platinum-doublet chemotherapy (PDCT) vs NIVO + PDCT as first-line (1L) treatment (tx) for stage IV or recurrent NSCLC: Results from the randomized phase II RELATIVITY-104 study

LBA53 Nivolumab (NIVO) plus relatlimab with platinum-doublet chemotherapy (PDCT) vs NIVO + PDCT as first-line (1L) treatment (tx) for stage IV or recurrent NSCLC: Results from the randomized phase II RELATIVITY-104 study

1992P Real-world (RW) characteristics and outcomes in patients (pts) with muscle-invasive urothelial carcinoma (MIUC) treated with adjuvant nivolumab (NIVO) with or without neoadjuvant chemotherapy (NAC)

1992P Real-world (RW) characteristics and outcomes in patients (pts) with muscle-invasive urothelial carcinoma (MIUC) treated with adjuvant nivolumab (NIVO) with or without neoadjuvant chemotherapy (NAC)

873P Nivolumab (NIVO) in the first-line (1L) or second-line (2L) and later (2L+) settings in patients (pts) with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Updated results from the German non-interventional study (NIS), HANNA

873P Nivolumab (NIVO) in the first-line (1L) or second-line (2L) and later (2L+) settings in patients (pts) with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Updated results from the German non-interventional study (NIS), HANNA

541P Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Subgroup efficacy and expanded safety analyses from CheckMate 8HW

541P Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Subgroup efficacy and expanded safety analyses from CheckMate 8HW

1086P Intratumoral (IT) administration of autologous CD1c(BDCA-1)+/CD141(BDCA-3)+myeloid dendritic cells (myDC) with the immunologic adjuvant AS01B plus ipilimumab (IPI) and IV nivolumab (NIVO) in patients with refractory advanced melanoma: A phase Ib clinical trial

1086P Intratumoral (IT) administration of autologous CD1c(BDCA-1)+/CD141(BDCA-3)+myeloid dendritic cells (myDC) with the immunologic adjuvant AS01B plus ipilimumab (IPI) and IV nivolumab (NIVO) in patients with refractory advanced melanoma: A phase Ib clinical trial

965MO Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line (1L) treatment for unresectable hepatocellular carcinoma (uHCC): Expanded analyses from CheckMate 9DW

965MO Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line (1L) treatment for unresectable hepatocellular carcinoma (uHCC): Expanded analyses from CheckMate 9DW

1317P Real-world immunotherapy (IO) rechallenge outcomes with nivolumab (NIV) in advanced non-small cell lung cancer (aNSCLC) in France: LIST study interim results

1317P Real-world immunotherapy (IO) rechallenge outcomes with nivolumab (NIV) in advanced non-small cell lung cancer (aNSCLC) in France: LIST study interim results

441O A phase I clinical trial on the intracranial administration of autologous CD1c(BDCA-1)+ /CD141(BDCA-3)+ myeloid dendritic cells (myDC) in combination with ipilimumab (IPI) and nivolumab (NIVO) in patients with recurrent high-grade glioma (rHGG)

441O A phase I clinical trial on the intracranial administration of autologous CD1c(BDCA-1)+ /CD141(BDCA-3)+ myeloid dendritic cells (myDC) in combination with ipilimumab (IPI) and nivolumab (NIVO) in patients with recurrent high-grade glioma (rHGG)

LBA30 ATHENA-COMBO, a phase III, randomized trial comparing rucaparib (RUCA) + nivolumab (NIVO) combination therapy vs RUCA monotherapy as maintenance treatment in patients (pts) with newly diagnosed ovarian cancer (OC)

LBA30 ATHENA-COMBO, a phase III, randomized trial comparing rucaparib (RUCA) + nivolumab (NIVO) combination therapy vs RUCA monotherapy as maintenance treatment in patients (pts) with newly diagnosed ovarian cancer (OC)

1646P A multicohort phase II trial of androgen deprivation therapy (ADT), docetaxel (DOCE) and nivolumab (NIVO) in patients (pts) with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) enriched for inflamed tumours and DNA damage repair (DDR) alterations: Cohort 3 results

1646P A multicohort phase II trial of androgen deprivation therapy (ADT), docetaxel (DOCE) and nivolumab (NIVO) in patients (pts) with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) enriched for inflamed tumours and DNA damage repair (DDR) alterations: Cohort 3 results

22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs)

Abstract Background Adverse events (AEs) can limit treatment immune checkpoint inhibitors (ICI) efficacy and worsen patient outcomes. Our group recently identified a germline IL7 SNP as a potential biomarker for prediction of irAEs (Groha, Nat Med 2022). In the current study, we sought to replicate the association between this IL7 SNP (rs16906115) and AEs in two clinical trials of patients with cancer treated with ICI regimens. Methods In the CheckMate-025 (CM025) trial (NCT01668784), involving patients with metastatic renal cell carcinoma (mRCC) randomized to either nivolumab (NIVO) or everolimus (EVE), whole-exome sequencing (WES) data from tumor and peripheral blood samples were analyzed. The Cancer Genome Analysis pipeline was utilized to identify somatic alterations, and the STITCH pipeline was employed to determine SNP carrier status. In the BinTA-0037 (BTA-0037) trial (NCT03631706), focusing on patients with metastatic non-small cell lung cancer (mNSCLC), the carrier status of a surrogate SNP rs16906062 (R2=0.66) was determined from tumor WES in the pembrolizumab (PEMBRO) arm. Within each treatment arm, time to incident AEs were compared between carriers (SNP+) and non-carriers (SNP-) via multivariable Cox regression, controlling for age, sex, race, ECOG and sample purity. A SNP´treatment interaction term was also included in the entire CM025 cohort. Censoring for AEs occurred at death or last follow-up. A recurrent event analysis for AEs was conducted using the Andersen-Gill model, controlling for the same variables. Additionally, overall survival (OS) and progression-free survival (PFS) were also assessed. Results In total, 534 pts were included (NIVO: n=189, PEMBRO: n=152, EVE: n=193), among which 82 (15.4%) were SNP+. There were no differences in clinical and pathological characteristics between SNP+ and SNP-, except for sex (SNP+ 16.1% vs. SNP- 30.1% in females, P=0.046). Similarly, no differences in somatic alterations, including single nucleotide and copy number variants were seen between SNP+ and SNP- in CM025. SNP carrier status had no effect on OS nor PFS in all treatment arms (all P≥0.22). The rate of grade 2+ AEs was significantly higher in SNP+ vs. SNP- in the NIVO arm (Figure A, HR=2.91[1.48-5.72]), but not in the EVE (Figure B, control, non-ICI) arm (HR=0.63[0.3-1.29], SNP´treatment Pinteraction=0.002). Similarly, the rate of all grade AEs in the PEMBRO arm of BTA-0037 was higher in SNP+ vs. SNP- (Figure C, HR=2.30[1.60-4.60]). The rate of recurrent grade 2+ AEs was also significantly higher in SNP+ vs. SNP- in the NIVO arm (HR=3.43[1.83-6.43]), whereas a trend for fewer recurrent grade 2+ AEs was seen in SNP+ vs. SNP- in the EVE arm (HR=0.46[0.17-1.25], SNP´treatment Pinteraction=0.0005). Figure: Kaplan-Meier curves showing the cumulative rate of adverse events in the NIVO (A) and EVE (B) arms of CM025, as well as the PEMBRO arm of BTA0037 (C), in SNP- and SNP+. Conclusions The IL7 SNP (rs16906115) is associated with significantly higher rates of grade 2+ AEs, including recurrent events, in pts with mRCC or mNSCLC treated with single agent PD-1 inhibitors but not with non-ICI regimens, with no effect on survival and efficacy outcomes. These results confirm the SNP’s predictive potential as a biomarker for irAEs to guide therapeutic decisions in pts treated with ICIs.