Yervoy (ipilimumab)

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.

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.

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

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

P2, N=90, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Phase classification: P1 --> P2

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

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

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

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

P1, N=55, Completed, Anaveon AG | Recruiting --> Completed | N=80 --> 55 | Trial completion date: Jan 2025 --> Jul 2024

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.

P1, N=24, Active, not recruiting, University of Utah | Trial primary completion date: Apr 2025 --> Jan 2024

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

P2, N=67, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Recruiting --> Active, not recruiting

P1, N=18, Not yet recruiting, Emory University | Initiation date: Sep 2024 --> Dec 2024

P1, N=2, Completed, University of Michigan Rogel Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Jul 2024

P3, N=300, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=43, Recruiting, Andrew J. Armstrong, MD | Trial completion date: Jun 2027 --> Jun 2028 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=25, Recruiting, University of Utah | Not yet recruiting --> Recruiting | Initiation date: Aug 2024 --> Nov 2024

P1, N=11, Active, not recruiting, Dana-Farber Cancer Institute | N=20 --> 11

Studies have reported the efficacy of programmed cell death-1 inhibitors (e.g., nivolumab, pembrolizumab) and anti-cytotoxic T-lymphocyte-associated antigen 4 agents (e.g., ipilimumab) in treating malignant melanoma. Histopathological examination revealed no tumors or lymph node metastases, confirming a pathologic complete response. Given the rarity and poor prognosis of primary malignant melanoma of the esophagus, this case provides valuable insights for treatment strategies.

We describe an impressive response to IO combination immunotherapy with ipilimumab plus nivolumab (Ipi/nivo) in a patient with T-NEPC who had failed standard treatment approaches. The results of the next-generation sequencing DNA analysis demonstrated the presence of intermediary tumor burden, an ATM mutation and a rare SF3B1 (G742D) mutation, and served as rational for IO therapy in this patient. This case highlights the genetic profile of tumor with a rare combination of ATM and SF3B1 mutations that could be further explored as biomarkers for IO therapy in T-NEPC and other tumor types.

P3, N=855, Completed, Exelixis | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> May 2024

P1, N=19, Active, not recruiting, Patrick Ott, MD, PhD | Trial completion date: Sep 2026 --> May 2030

P2, N=45, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

P1/2, N=25, Completed, Inge Marie Svane | Unknown status --> Completed

We retrospectively analyzed the outcomes of combination therapy, including nivolumab plus ipilimumab or chemotherapy plus anti-programmed cell death 1 (PD-1) antibodies in our institute to identify biomarkers...In multivariable analysis, albumin level was significantly correlated with PFS in the cisplatin plus 5-fluorouracil (CF) plus pembrolizumab group...In chemotherapy combined with ICIs, NLR before the treatment was not associated with treatment efficacy, suggesting combination chemotherapy may be beneficial for EC patients with high NLR. NLR may be an indicator of immunocompetence in anti-tumor immunity and a convenient predictive biomarker for selecting appropriate treatments including ICIs.

A 40-year-old patient, diagnosed with stage IV non-oncogene addicted lung adenocarcinoma, with nivolumab-ipilimumab-chemotherapy as first-line treatment, developed a rare myocarditis-myositis-myasthenia gravis overlap syndrome...Treatment with oral prednisone, pyridostigmine, and IV Igs was started due to poor clinical response followed by methylprednisolone...This report aims to raise awareness among physicians about these serious side effects. A multidisciplinary approach led to clinical improvement and early intervention, optimizing patient outcomes.

P2, N=30, Active, not recruiting, Providence Health & Services | Trial completion date: Apr 2026 --> Jan 2026 | Trial primary completion date: Aug 2024 --> Jan 2025

P3, N=1175, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P2/3, N=135, Not yet recruiting, Linnaeus Therapeutics, Inc. | Phase classification: P3 --> P2/3

Patients with NSCLC harboring select AGAs, including EGFR and ALK alterations, have a higher risk for TF, shorter median time to TF, and diminished pathological regression after neoadjuvant ICIs. The suboptimal efficacy of neoadjuvant chemotherapy-sparing, ICI-based regimens in this patient subset underscores the importance of tumor molecular testing prior to initiation of neoadjuvant ICI therapy in patients with resectable NSCLC.

Immune checkpoint inhibitors (ICIs) have shown great success, with FDA-approved drugs like PD-1 inhibitors (Nivolumab, Pembrolizumab, Cemiplimab), PD-L1 inhibitors (Atezolizumab, Durvalumab, Avelumab), and CTLA-4 inhibitors (Ipilimumab, Tremelimumab), alongside LAG-3 inhibitor Relatlimab. This review aims to fill this gap by providing an analysis of the current clinical status of ICIs, emerging biomarkers, mechanisms of resistance, strategies to enhance therapeutic efficacy, and assessment of adverse effects. This review is crucial to furthering our understanding of ICIs and optimizing their application in cancer therapy.

To evaluate the efficacy of anti-programmed cell death 1 nivolumab and anti-cytotoxic lymphocyte-associated protein 4 ipilimumab in patients with aggressive thyroid carcinoma. However, the signal observed in ATC may merit further evaluation. ClinicalTrials.gov Identifier: NCT03246958.

P2, N=37, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=180 --> 37

Changes in tumor size and immune cell infiltration and activation are candidate predictive markers of pathologic response to neoadjuvant immunotherapy in patients with resectable HCC.