Yervoy (ipilimumab) / Ono Pharmaceutical, BMS - LARVOL DELTA

Nivolumab plus low-dose ipilimumab in hypermutated HER2-negative metastatic breast cancer: a phase II trial (NIMBUS). (PubMed, Nat Commun) - P2 | "In summary, some patients with hypermutated HER2-negative MBC experience extended clinical benefit with a dual immunotherapy regimen; a higher TMB, and additional genomic and microbiome biomarkers may optimize patient selection for therapy with nivolumab plus low-dose ipilimumab. (Funded by Bristol Myers Squibb; ClinicalTrials.gov identifier, NCT03789110)."

Biomarker • IO biomarker • Journal • P2 data • Tumor mutational burden • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PD-L1 • PTEN • TMB

CA209-8TY trial, a randomized phase 2 trial of nivolumab and ipilimumab with or without stereotactic body radiation therapy in metastatic castration-resistant prostate cancer. (ASCO 2025) - P2 | "Objective responses were demonstrated in patients with mCRPC treated with combination ICI, however PFS was short and treatment-related toxicity significant. While the addition of SBRT was safe, it did not improve treatment outcomes in this study. Further analyses are ongoing to identify patients with mCRPC, who are most likely to respond to ICI."

Clinical • IO biomarker • Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

177Lu-PSMA-617 with ipilimumab (ipi) and nivolumab (nivo) in metastatic castration-resistant prostate cancer (mCRPC): An investigator-initiated phase 2 trial (EVOLUTION; ANZUP2001). (ASCO 2025) - P2 | "Median age was 70 years [range: 45-83]; 80% had prior docetaxel. LuPSMA+ICI was associated with improved PSA-PFS 12m in mCRPC. The spectrum of AEs were keeping with established toxicities however significantly higher with LuPSMA+ICI, and frequency of ICI-related myocarditis lead to early trial cessation. *Safety population."

Metastases • P2 data • Anemia • Castration-Resistant Prostate Cancer • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Hepatology • Immunology • Infectious Disease • Oncology • Pneumonia • Prostate Cancer • Respiratory Diseases • Septic Shock • Solid Tumor • Thrombocytopenia

Gotistobart vs Docetaxel in Metastatic Squamous NSCLC After PD-(l)1 Progression: Updated Overall Survival of the stage 1 of PRESERVE-003 (IASLC-WCLC 2026) - "Population PK model-predicted exposure metrics indicated that gotistobart achieved approximately 2-fold higher C max and 3-fold higher C through and AUC than ipilimumab at the same dosing regimen. These results support ongoing evaluation of gotistobart in the pivotal part of the PRESERVE-003 trial. $$graphic_1BA59175-034E-4920-8346-FF8472A061B8$$"

Clinical • Metastases • Gastroenterology • Gastrointestinal Disorder • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Solid Tumor

Clinical Outcomes of the Phase III Lonestar Trial: Local Consolidation Therapy After Nivolumab Plus Ipilimumab in NSCLC (IASLC-WCLC 2026) - P3 | "Conclusions : To our knowledge, this is the largest randomized trial of LCT added to nivolumab plus ipilimumab. Adding LCT after induction dual checkpoint blockade was feasible but did not improve OS or PFS in an unselected population, including patients with oligometastatic disease."

Clinical • Clinical data • IO biomarker • Late-breaking abstract • P3 data • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Pneumonia • Solid Tumor • ALK • EGFR

Tumour Extrinsic Regulation of Neutrophils Sensitize Mesotheliomas to AXL and PD1 Inhibition inMIST3, a Phase II Clinical Trial (IASLC-WCLC 2026) - P2 | "Introduction : Immune checkpoint blockade (ICB) with ipilimumab and nivolumab is a front-line standard of care in patients with mesothelioma...We evaluated AXL and programmed death 1 (PD1) inhibition (AXL-PD1) with bemcentinib and pembrolizumab respectively, in a phase IIA clinical trial in patients with ICB naïve-relapsed mesothelioma (MIST3, NCT03654833 )...Gut microbiota predicted tumour responsiveness (ROC AUC=0.959, p=0.0004), and positively correlated with neutrophil infiltration, IRF3 and TLR2. Conclusions : In summary, a gut microbiota-neutrophil axis regulates sensitivity to AXL-PD1, highlighting opportunities to improve ICB therapeutic effectiveness through promotion of innate anti-tumour immunity."

Clinical • P2 data • Mesothelioma • Oncology • Solid Tumor • AXL • FLI1 • NAB2 • NF2 • SPI1 • TLR2

Development and external validation of a new prognostic model for metastatic clear cell renal cell carcinoma: a preregistered analysis using data from randomised clinical trials in the checkpoint inhibitor era. (PubMed, Lancet Oncol) - "The CPI2 model, using 14 readily available clinical parameters, demonstrated improvement in discriminative accuracy compared with the IMDC model. This classification should be further validated in other trial and observational populations and be used to reanalyse heterogeneity of treatment effects of immune checkpoint inhibitor-based combination regimens in trials shaping the current and future treatment landscape."

Checkpoint inhibition • IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

The Role of Immunotherapy in the Treatment of Metastatic Gastric Cancer (IASGO 2026) - "HERIZON-GEA-01 showed thatzanidatamab plus chemotherapy improved progression-free survival versus trastuzumab pluschemotherapy, while adding tislelizumab also produced an encouraging overall-survival benefit...Nivolumab plus ipilimumab failed to improve survival in CheckMate 649, andATTRACTION-6 increased response rate without improving overall survival and caused greater toxicity.However, in MSI-H/dMMR advanced G/GEJC, the phase II NO LIMIT trial showed robust and durableactivity with first-line nivolumab plus low-dose ipilimumab, supporting biomarker-defined dualcheckpoint blockade...The EP4 antagonist ONO-4578 plus nivolumab and chemotherapy showed encouragingphase II activity. ASP2138, a CLDN18.2/CD3 bispecific T-cell engager, is being evaluated withpembrolizumab and chemotherapy, while zolbetuximab plus nivolumab and chemotherapy showedpromising activity in ILUSTRO and is being tested in phase III LUCERNA. Future progress will depend on biomarker-driven combinations..."

IO biomarker • Metastases • Gastric Cancer • Oncology • Solid Tumor • CLDN18 • HER-2 • MSI • PD-L1 • TIGIT

First-line systemic therapy for advanced or metastatic esophageal squamous cell carcinoma: clinical implications for treatment selection after KEYNOTE-590, CheckMate 648, and RATIONALE-306. (PubMed, Clin J Gastroenterol) - "KEYNOTE-590 enrolled both ESCC and adenocarcinoma and established pembrolizumab plus chemotherapy as a durable chemoimmunotherapy standard across histologic subtypes. CheckMate 648, focused on ESCC, showed that nivolumab plus chemotherapy and nivolumab plus ipilimumab both improve overall survival (OS), although the patterns of benefit are distinct: progression-free survival (PFS) benefit was observed with nivolumab plus chemotherapy but not with nivolumab plus ipilimumab. RATIONALE-306 subsequently added tislelizumab plus chemotherapy as another evidence-based first-line option in ESCC...This review summarizes the evidence supporting current first-line treatment selection and its implications for daily clinical practice. Key issues addressed include practical distinctions between chemoimmunotherapy and dual immune checkpoint blockade, harmonization of PD-L1 assessment, platinum-backbone selection, and the optimization of treatment sequencing after first-line immunotherapy."

IO biomarker • Journal • Review • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Long-term survival and cure fraction in patients with advanced hepatocellular carcinoma under immunotherapy in randomized controlled trials and real-world data. (PubMed, Clin Cancer Res) - "Across trials and real-world data, ICIs combinations achieve long-term survival in 10-15% of advanced HCC patients, with cure fractions of 7-9%."

Journal • Real-world evidence • Hepatitis C • Hepatocellular Cancer • Infectious Disease • Oncology • Solid Tumor

Liquid TIL (L-TIL) Plus Tislelizumab for Anti-PD-1-Resistant Advanced NSCLC: A Multicenter Single-Arm Phase II Trial (IASLC-WCLC 2026) - P2 | "Randomized phase III study has shown that TIL achieved higher ORR (49% vs 21%) and longer median PFS (7.2 vs 3.1 months; HR 0.50) than ipilimumab therapy (Rohaan et al.,2022)...Data from a single-arm phase I study in advanced NSCLC patients who had progressed from nivolumab demonstrated that 2 of 13 patients achieved sustained complete response (CR) for over 1.5 years by TIL therapy, the remaining 11 experienced a reduction in tumor burden(Creelan et al., 2021)...ORR will be summarized with Clopper-Pearson exact 95% confidence intervals, and time-to-event endpoints (PFS, OS, DOR) will be analyzed using Kaplan-Meier methods. $$graphic_9B5E6EE9-2610-4CA0-BF7E-5E14ECE8AD37$$"

Clinical • Metastases • P2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor

Survival in unresectable hepatocellular carcinoma: Comparison of four treatments based on patients reconstructed from Kaplan-Meier curves of randomized trials. (PubMed, World J Gastrointest Pharmacol Ther) - "Our study compared the efficacy of the main first-line treatments recommended for unresectable HCC. While we were able to rank the magnitude of efficacy across these treatments, the intrinsic limitations of our methods (primarily the reconstruction of IPD and the indirect nature of the treatment comparisons) should be borne in mind."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Clinical Characteristics and Risk Factors for Severe Immune-Related Liver Injury Following Nivolumab and Ipilimumab Combination Therapy. (PubMed, Antibodies (Basel)) - "Background: Combination therapy with nivolumab and ipilimumab (Nivo-Ipi) has substantially improved outcomes in several advanced malignancies but is frequently associated with early-onset, severe immune-related liver injury (irAE-LI). Pretreatment KL-6 measurement may facilitate risk stratification before Nivo-Ipi therapy. In patients with steroid-refractory or relapsing severe irAE-LI, early introduction of mycophenolate mofetil together with CMV screening may improve clinical management."

Journal • Cytomegalovirus Infection • Hematological Disorders • Hepatology • Liver Failure • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Model-based clinical pharmacology profiling of subcutaneous nivolumab in renal cell carcinoma: Bridging to alternative dosing regimens and indications. (PubMed, Clin Pharmacol Ther) - P3 | "The MIDD approach provided an integrated and computationally efficient framework to characterize nivolumab SC/IV PK. Simulation-based analyses confirmed comparable benefit-risk profiles of nivolumab SC in adults across solid tumor indications and led to FDA approval of nivolumab SC in existing adult IV indications (except for nivolumab in combination with ipilimumab)."

Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

G360-IIT: Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy (clinicaltrials.gov) - P2 | N=5 | Terminated | Sponsor: Hackensack Meridian Health | N=108 ➔ 5 | Trial completion date: Apr 2027 ➔ Aug 2026 | Recruiting ➔ Terminated | Trial primary completion date: Apr 2027 ➔ Aug 2026; Slow Accrual

Circulating tumor DNA • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Phase 2 multicenter trial of chemoimmunotherapy for patients with neuroendocrine or aggressive variant metastatic prostate cancer (CHAMP). (ASCO 2026) - P2 | " We conducted a multicenter, phase II trial evaluating cabazitaxel, carboplatin, ipilimumab, and nivolumab (NCT04709276) in patients with metastatic NEPC/AVPC defined by histologic, clinical, or molecular features. Dual PD-1/CTLA4 immune checkpoint blockade with platinum doublet chemotherapy is effective in patients with AVPC/NEPC, resulting in greater efficacy than expected with historic platinum chemotherapy alone, and with acceptable toxicity given disease risk. These results support randomized controlled clinical trials of chemoimmunotherapy in patients with NEPC/AVPC."

Clinical • Metastases • P2 data • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Immunology • Infectious Disease • Lung Cancer • Neutropenia • Oncology • Prostate Cancer • Septic Shock • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • CTLA4

Nivolumab plus ipilimumab for chemotherapy-refractory metastatic castration-resistant prostate cancer: results from the randomized portion of the phase 2 CheckMate 650 trial. (PubMed, Nat Commun) - P2 | "We report on the randomized portion of the phase 2, open-label CheckMate 650 trial (NCT02985957), in which docetaxel-experienced, biologically male patients with chemotherapy-refractory metastatic castration-resistant prostate cancer were randomized 2:2:1:2 to nivolumab 3 mg /kg plus ipilimumab 1 mg /kg (n = 73), nivolumab 1 mg /kg plus ipilimumab 3 mg /kg (n = 74), ipilimumab 3 mg /kg (n = 38), or cabazitaxel (n = 74). Preliminary post hoc biomarker analyses in patients who received treatment with any immunotherapy regimen (i.e., treated with either of the nivolumab plus ipilimumab regimens or with ipilimumab alone, n = 12) identified a transcriptional signature, derived from the most highly expressed genes across cell types within select perivascular immune niches (comprising CD31+ endothelial, CD14+HLA-DR+ myeloid, and CD4+ and CD8+ T cells), which was associated with prolonged overall survival. These results provide further evidence of antitumor activity with..."

IO biomarker • Journal • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD14 • CD31 • CD8 • PECAM1

Nivolumab plus ipilimumab for the treatment of post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC): Additional results from the randomized phase 2 CheckMate 650 trial. (ASCO-GU 2023) - P2 | "Here, we report results from pts with post-CT mCRPC receiving alternative NIVO+IPI dosing regimens vs IPI alone vs cabazitaxel (CABA) in CheckMate 650. Newly enrolled pts previously treated with docetaxel for mCRPC were randomized 2:2:1:2 to cohorts D1 (NIVO 3 mg/kg [N3] + IPI 1 mg/kg [I1] Q3W × 4 doses then NIVO 480 mg Q4W), D2 (N1 Q3W × 8 doses + I3 Q6W × 4 doses then NIVO 480 mg Q4W), D3 (I3 Q3W × 4 doses), or D4 (CABA 20 or 25 mg/m2 Q3W + prednisone 10 mg × 10 doses)... These results further support the clinical activity of NIVO+IPI in select pts with post-CT mCRPC. Detailed evaluations of the characteristics of responders to NIVO+IPI, including more expansive biomarker analyses, are warranted. Clinical trial information: NCT02985957."

Clinical • Metastases • P2 data • Tumor mutational burden • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • TMB

Testing the Combination of XL184 (Cabozantinib), Nivolumab, and Ipilimumab for Poorly Differentiated Neuroendocrine Tumors (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Aug 2026 ➔ Sep 2027

Trial completion date • Endocrine Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor

Four-Year outcomes of first-line Nivolumab plus ipilimumab for 6 months versus continuation in patients with advanced non-small-cell lung cancer Results of the randomized IFCT-1701 "DICIPLE" Phase III trial. (PubMed, J Thorac Oncol) - "Stopping IO combination at 6 months in DC patients showed no survival harm at 4 years, reduced severe irAEs, and delayed QoL deterioration."

Journal • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Complete remission of a therapy-refractory Kaposi's sarcoma under off-label therapy with ipilimumab and nivolumab (ADO 2026) - No abstract available

Clinical • Kaposi Sarcoma • Sarcoma • Solid Tumor

Clinical outcomes with nivolumab/ipilimumab (nivo/ipi) with or without CBM588 in metastatic renal cell carcinoma (mRCC): Long-term follow-up of a randomized phase Ib clinical trial (IKCS 2022) - "Although limited by sample size, nivo/ipi/CBM588 demonstrated superior clinical activity over nivo/ipi. PFS and ORR with nivo/ipi/cbm588 also exceeded those observed with nivo/ipi in historical datasets. Larger efforts investigating gut microbiome modulation via CBM588 are warranted."

Clinical • Clinical data • P1 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Nivolumab, ipilimumab and bevacizumab together with 2 cycles of induction chemotherapy in patients with non-squamous NSCLC and untreated brain metastases (CA209-7WF/Break B5-BM-NSCLC/AIO-TRK-0220/ass) (ESMO 2025) - P2 | "Pts received nivolumab (360 mg, q3w), ipilimumab (1 mg/kg, q6w) and bevacizumab (400 mg, q3w) concomitantly with 2 cycles of chemotherapy [carboplatin (AUC 5, q3w) plus nab-paclitaxel (100 mg/m 2 , q1w)]. Most common adverse events grade ≥ 3 were pneumonia (6 pts), neutropenia (5 pts), alanine aminotransferase increased (4 pts), acute kidney injury (3 pts), sepsis (3 pts) and infection (3 pts). Conclusions The Break-B5 trial demonstrated promising intracranial activity in active (asymptomatic + symptomatic) BMs of NSCLC along with a manageable safety profile."

Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Correlation of ten-year survival with cell-free DNA methylation of melanoma patients with asymptomatic brain metastases treated with nivolumab plus ipilimumab: The multicenter phase III NIBIT-M2 trial. (ASCO 2026) - P3 | " The NIBIT-M2 study recruited melanoma pts with active, untreated, asymptomatic BM from 9 Italian Centers, randomized (1:1:1) to receive fotemustine (F) (Arm A), I+F (Arm B), or I+N (Arm C). The 10-y results of the NIBIT-M2 study, with the longest follow-up available to date in melanoma pts with asymptomatic BM treated with I+N, continue to show persistent long-term therapeutic efficacy of the combination. Plasma-derived TF and T-meth Score may predict long-term survival of melanoma pts with asymptomatic BM treated with I+N."

cfDNA • Clinical • Epigenetic controller • P3 data • Melanoma • Solid Tumor

Phase III randomized trial evaluating tilsotolimod in combination with ipilimumab versus ipilimumab alone in patients with advanced refractory melanoma (ILLUMINATE 301). (ASCO 2024) - P3 | "Adding tilsotolimod to ipilimumab did not improve response or OS in patients with PD-1 refractory advanced melanoma. However, the results represent the largest prospective dataset reported to date on using ipilimumab in this setting and are a valuable addition to the knowledge base."

Clinical • Combination therapy • Late-breaking abstract • Metastases • P3 data • Melanoma • Oncology • Solid Tumor