Opdivo (nivolumab)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

BACKGROUNDInhibition of Bruton's tyrosine kinase with ibrutinib blocks the function of myeloid-derived suppressor cells (MDSC). The addition of nivolumab significantly increased circulating NK and CD8+ T cells and increased CD8+ T cell proliferation. Exploratory analyses suggest that MDSC and T cell gene expression and TCR repertoire diversity were differentially affected by BTK inhibition according to patient response.CONCLUSIONIbrutinib and nivolumab were well tolerated and affected MDSC and T cell function in patients with solid metastatic tumors.TRIAL REGISTRATIONClinicalTrials.gov NCT03525925.FUNDINGNIH; National Cancer Institute Cancer; National Center for Advancing Translational Sciences; Pelotonia.

These monoclonal antibodies target immune checkpoints, including cytotoxic T-lymphocyte-associated protein 4 (ipilimumab and tremelimumab), programmed death 1 (nivolumab, pembrolizumab, cemiplimab, and dostarlimab), programmed death ligand 1 (atezolizumab, avelumab, and durvalumab), and lymphocyte activation gene 3 (relatlimab), and effectively augment the immune response against tumor cells. Despite clinical improvements with immunomodulatory therapy, with corticosteroids the mainstay of treatment, mortality remains high, particularly in those with associated myocarditis or respiratory failure requiring intubation, where mortality occurs in up to 50%. ICI withdrawal can lead to cancer progression and death, highlighting a need for improved approaches to ICI rechallenge, performed in limited patients with variable success to date.

Our real-world data indicate that combined CTLA-4 and PD-1 blockade is most beneficial for patients with multi-organ metastasis, while those with oligo-organ metastasis fare better with PD-1 monotherapy. The underlying reasons for these observations-whether they are due to differences in the characteristics of multi- and oligo-metastatic melanomas or the risk-benefit profile of the therapies-remain to be elucidated. These findings underscore the need for a nuanced approach to treatment regimens for stage IV melanoma patients.

P1, N=5, Terminated, Roswell Park Cancer Institute | Active, not recruiting --> Terminated; Low accrual

Herein, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti-PD-1 nivolumab, trastuzumab, and FOLFOX chemotherapy (FOLFOX arm) in comparison to a chemotherapy-free regimen involving nivolumab, trastuzumab, and the anti-CTLA-4 ipilimumab (Ipi arm) in the first-line setting for advanced disease...Furthermore, a low NLR characterized patients benefiting from immune- and targeted therapy without the need for additional chemotherapy. This data suggests that patient selection based on inflammatory stress-driven immune changes could help to customize first-line treatment in patients with advanced HER2-positive EGA to potentially improve long-term survival.

P=N/A, N=160, Recruiting, University Hospital, Montpellier | Not yet recruiting --> Recruiting

P1, N=26, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Apr 2025 --> Nov 2024 | Trial primary completion date: Apr 2025 --> Nov 2024

P2, N=15, Active, not recruiting, National Cancer Institute (NCI) | N=40 --> 15 | Trial completion date: Sep 2027 --> Nov 2025 | Trial primary completion date: Sep 2027 --> Sep 2024

P1, N=353, Completed, Eli Lilly and Company | Active, not recruiting --> Completed

The efficacy of nivolumab plus chemotherapy did not vary according to claudin 18.2 positivity. The clinical benefit of nivolumab plus chemotherapy over chemotherapy was consistently observed in claudin 18.2-positive and -negative gastric cancer cases.

While combination therapies, including immunotherapies, have shown positive outcomes, immune checkpoint inhibitors like nivolumab and pembrolizumab have demonstrated encouraging antitumor activity. Additionally, targeting the c-MET pathway has proven effective in certain papillary RCC. Further research is warranted to establish optimal treatment strategies and improve outcomes for patients with non-clear cell RCC. Systemic therapy for non-clear cell RCC is complex and evolving. Further research is needed to delineate optimal treatment strategies for different histological subtypes and improve patient outcomes.

P2, N=29, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Oct 2024 --> Oct 2026

P1/2, N=162, Recruiting, Bristol-Myers Squibb | Trial primary completion date: Jun 2024 --> Oct 2025

Correlative studies include genomic characterization of tumors, assessment of immune infiltration of tumor microenvironment, and serial circulating cell-free DNA and immune biomarkers. ClinicalTrials.gov Identifier: NCT05795244.

Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.

P1, N=32, Active, not recruiting, Ono Pharmaceutical Co. Ltd | Trial completion date: May 2025 --> Dec 2026 | Trial primary completion date: May 2025 --> Dec 2026

P1/2, N=96, Recruiting, The Netherlands Cancer Institute | Not yet recruiting --> Recruiting | Trial completion date: May 2026 --> Mar 2034 | Trial primary completion date: Feb 2026 --> Jul 2029

P2, N=23, Recruiting, Ono Pharmaceutical Co. Ltd | Not yet recruiting --> Recruiting

P2, N=52, Recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=18, Active, not recruiting, Washington University School of Medicine | Trial completion date: Mar 2026 --> Sep 2025

P1, N=5, Active, not recruiting, Roswell Park Cancer Institute | Recruiting --> Active, not recruiting | N=12 --> 5

P1/2, N=39, Completed, Salma Sabbour | Active, not recruiting --> Completed

P2, N=23, Not yet recruiting, University of California, Irvine

P1/2, N=30, Not yet recruiting, M.D. Anderson Cancer Center

P3, N=700, Recruiting, IFOM ETS - The AIRC Institute of Molecular Oncology | Not yet recruiting --> Recruiting

P1/2, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=12 --> 19

P1, N=14, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

P3, N=183, Completed, Krankenhaus Nordwest | Active, not recruiting --> Completed | Trial completion date: Feb 2026 --> Aug 2024 | Trial primary completion date: Feb 2026 --> Aug 2024

P1/2, N=100, Completed, Enterome | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Mar 2024 | Trial primary completion date: Dec 2024 --> Jan 2024

P1/2, N=70, Terminated, Enterome | Active, not recruiting --> Terminated; Strategic decision

P2, N=222, Completed, ETOP IBCSG Partners Foundation | Active, not recruiting --> Completed

P2/3, N=280, Recruiting, Replimune Inc. | Not yet recruiting --> Recruiting

P2, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=30, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting

P1, N=30, Suspended, City of Hope Medical Center | Recruiting --> Suspended

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.

(Trial registration: ClinicalTrials.gov NCT04159896. Registration date: November 12, 2019.).

P2, N=155, Active, not recruiting, City of Hope Medical Center | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024

The combination of Nivo + DA R-EPOCH demonstrated a high rate of durable PFS as frontline treatment for specific subgroups of patients with LBCL, including high risk populations. Promising results were observed in patients with PMBCL and DHL, supporting further study. While irAEs were observed consistent with the known Nivo safety profile, Nivo + DA R-EPOCH was feasible at standard dosing.

P1, N=20, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Sep 2026

P=N/A, N=30, Recruiting, John Kirkwood | Not yet recruiting --> Recruiting