nivolumab

Overview

Nivolumab is an anti-PD-1 monoclonal antibody immune checkpoint inhibitor with broad FDA approvals across melanoma, NSCLC, renal cell carcinoma, colorectal cancer (MSI-H), hepatocellular carcinoma, gastric/esophageal cancer, mesothelioma (with ipilimumab), and others.

Evidence in the corpus

  • In a phase 2 trial (n=35) of nivolumab in dMMR/MSI-H gynecologic cancers (endometrial, ovarian, cervical), ORR was 58.8% and 24-month PFS rate was 64.7%, meeting pre-specified endpoints; TMB and PD-L1 did not predict response within dMMR-selected patients PMID:38653864.
  • Dysfunctional (CD8+PD-1+) and terminally dysfunctional (CD8+PD-1+TOX+) T cells, and their spatial interaction with PD-L1+ cells, are candidate predictive biomarkers for nivolumab response; a 3–4 marker IHC panel (CD8, PD-1, TOX, PD-L1) could be clinically applicable PMID:38653864.
  • Somatic mutations in MEGF8 (32% vs 0% in responders/non-responders, P=0.027) and SETD1B (58% vs 14%, P=0.015) are candidate genomic response biomarkers in dMMR gynecologic cancers treated with nivolumab PMID:38653864.
  • In genomic near-haploidization (GNH) diffuse pleural mesothelioma, ipilimumab+nivolumab achieved 2/3 (67%) partial responses in GNH patients vs 1/44 (2%) in non-GNH patients PMID:38630790.
  • In a phase 2 trial (NCT03521570, n=51) of IMRT reirradiation combined with concurrent and maintenance nivolumab in recurrent/second-primary HNSC, estimated 1-year PFS was 61.7% (95% CI 49.2%–77.4%), rejecting the historical null of 43.8% (1-arm log-rank P=.002). Median PFS 20.7 months, 2-year OS 48.4%; only 12% grade ≥3 treatment-related AEs and no grade 5 events PMID:38780927.
  • PD-L1 combined positive score (22C3, CPS <20 vs ≥20) did not predict PFS or OS benefit in this reirradiation + nivolumab context, diverging from the recurrent/metastatic HNSCC setting PMID:38780927.
  • The ROBIN consortium (ROBIN white paper) identifies nivolumab (PD-1 blockade) as one of the systemic agents being combined with radiation therapy, alongside adenosine-pathway inhibition and antibody-drug conjugates, as a priority direction for radiation-immunotherapy combination trials PMID:41941260.
  • Received by 1 metastatic gallbladder carcinoma patient (and 1 patient received ipilimumab/nivolumab combination) among 12 ICI-treated patients in the MSK GBC cohort (n=233); 42% (5/12) showed evidence of ICI response PMID:36228155
  • Nivolumab+cabozantinib data were not available in the HiTME training cohorts; this was cited as an open limitation in the ccRCC IO/TKI decision-tree model PMID:22138691
  • CheckMate 040 in HCC: nivolumab investigator-assessed ORR 20%, median duration of response 9.9 months (n=214 dose-expansion); OS 15.6 months in second-line; FDA accelerated approval based on 154 sorafenib-pretreated patients (ORR 14.3% RECIST 1.1, 18.2% mRECIST, DoR 16.6 months); PD-L1 IHC does not predict response in HCC PMID:24798001
  • Anti-PD-1 ICI listed among investigational agents for recurrent/metastatic NPC; PD-1/PD-L1 monotherapy ORR approximately 15–20% in NPC; relatlimab + nivolumab in randomized REMAIN trial for LAG-3 co-blockade PMID:24952746
  • CD274 (PD-L1) focal amplifications in BRAF-mutant melanoma subtype and high PDCD1/PD-L1 expression in Immune transcriptomic subclass (51% of 329 TCGA cases) identified as rationale for checkpoint blockade including nivolumab; LScore + LCK bivariate prognostic model proposed for adjuvant-therapy decisions PMID:26091043
  • Hugo et al. (n=38 metastatic melanoma): nivolumab (and pembrolizumab) anti-PD-1 therapy; IPRES transcriptional program (mesenchymal transition, angiogenesis, wound healing) enriched in innate non-responders; IPRES co-enrichment not predictive in anti-CTLA-4 cohort (skcm_dfci_2015), distinguishing anti-PD-1 from anti-CTLA-4 resistance mechanisms; 14/38 patients had prior MAPKi therapy PMID:26997480
  • In a 68-patient melanoma cohort treated with nivolumab (ipilimumab-naive and ipilimumab-progressed), pre-therapy clonal mutation load predicted OS and response only in ipilimumab-naive patients; on-therapy genomic contraction at week 4 predicted response (CR/PR vs PD p=5.87e-5) better than raw TMB change PMID:29033130
  • Authors advocate considering anti-PD-1 agents including nivolumab early in MSI-H EGC, where median PFS on first-line chemotherapy was only 4.8 months but multiple durable immunotherapy responses were observed PMID:29122777
  • Used as anti-PD-1 monotherapy in the discovery and validation ccRCC cohorts (n=35 and n=63) studied for PBRM1 LOF as a biomarker of response; PBRM1-biallelic-loss patients showed significantly prolonged OS (log-rank p=0.0074) and PFS (p=0.029) on anti-PD-(L)1 therapy including nivolumab PMID:29301960
  • One of the anti-PD-(L)1 agents used in the 240-patient MSK NSCLC cohort; TMB measured by MSK-IMPACT correlated with durable clinical benefit across nivolumab, pembrolizumab, atezolizumab, durvalumab, and ipilimumab-treated patients (Spearman r=0.86 vs WES, DCB rate 38.6% above vs 25.1% below median TMB, p=0.009) PMID:29337640

Resistance mechanisms

  • IPRES (Innate anti-PD-1 Resistance) transcriptional program — co-enriched mesenchymal, angiogenic, hypoxia, and wound-healing signatures — enriched in 9/13 non-responding vs 1/15 responding pretreatment melanoma biopsies; IPRES was NOT predictive in an anti-CTLA-4 cohort, indicating mechanism-specific resistance distinct from anti-PD-1 PMID:26997480.
  • Non-GNH diffuse pleural mesothelioma shows very poor response rates (2%) to nivolumab-based or pembrolizumab immunotherapy PMID:38630790.
  • Within dMMR-selected gynecologic cancer patients, TMB and PD-L1 expression do not identify responders vs non-responders, suggesting these biomarkers are insufficient for further stratification in this population PMID:38653864.

Cancer types (linked)

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36228155

This page was processed by crosslinker on 2026-05-14. - PMID:22138691

This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:24952746

This page was processed by crosslinker on 2026-05-14. - PMID:26091043

This page was processed by crosslinker on 2026-05-14. - PMID:26997480

This page was processed by entity-page-writer on 2026-05-15. - PMID:29033130

This page was processed by wiki-cli on 2026-05-15. - PMID:29122777

This page was processed by wiki-cli on 2026-05-15. - PMID:29301960

This page was processed by wiki-cli on 2026-05-15. - PMID:29337640

This page was processed by entity-page-writer on 2026-05-15.