Yervoy (ipilimumab)

P1, N=27, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2025 --> Jun 2027 | Trial primary completion date: Aug 2025 --> Jun 2027

P2, N=10, Terminated, M.D. Anderson Cancer Center | Trial completion date: Jul 2027 --> Nov 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2027 --> Nov 2025; The study met its prespecified futility criteria during the prespecified interim futility analysis after enrolling the first cohort of 10 patients.

Individual patient data (IPD) from the KEYNOTE-177 and CheckMate-8HW trials were collected with IPDfromKM and used to develop a Markov model with a 30-year duration and three mutually exclusive health states, providing a framework for the evaluation of the cost-effectiveness of first-line nivolumab together with ipilimumab, pembrolizumab, and chemotherapy for treating MSI-H/dMMR advanced CRC. In addition, the established model is stable. First-line immunotherapeutic treatments for MSI-H/dMMR advanced CRC cases in the USA appears to be cost-effective, with a dual-immunotherapeutic regimen consisting of nivolumab plus ipilimumab being preferable.

P=N/A, N=232, Completed, Ankara Etlik City Hospital

In the INCREASE trial, neoadjuvant IPI/NIVO combined with CRT for patients with T3-4N0-2 NSCLC elicited enhanced immune responses in TDLN despite exposure to high dose radiation. Even though radiation-induced fibrosis was evident in high dose TDLN, the immune responses were not diminished when compared with low dose TDLN. These findings underscore the resilience of TDLN immunological function under intense radiation exposure.

Our findings indicate that rela/nivo may remain active following anti-PD-1 or ipi/nivo therapy. Additionally, our results suggest that sequencing ipi/nivo before rela/nivo may yield better outcomes than starting with rela/nivo. Patients who respond to the first combination regimen appear to derive greater benefit from the second. Further efforts are needed to optimize sequencing strategies in advanced melanoma, and future studies should consider the impact of prior treatment outcomes.

Since the first CTLA-4 inhibitor ipilimumab started the first clinical trial in 2000, immune checkpoint inhibitor (ICI) therapy has gradually emerged as the most successful and widely applied strategy in the field of cancer immunotherapy, revolutionizing treatment paradigms across a broad spectrum of malignancies. Recently, the approvals of monoclonal antibodies targeting lymphocyte activation gene-3 (LAG-3) and novel bispecific antibodies targeting immune checkpoints may indicate the next wave of ICI agents development in cancer immunotherapy. In this review, we aimed to provide a comprehensive overview and in-depth discussion covering the current ICI treatment landscape in the past 26 years (2000-2025), indications and limitations of efficacy-predicting biomarkers, immune-related adverse events, resistance mechanisms and overcoming strategies, as well as future directions of ICI therapy.

Selective pharmacologic inhibition of p300 suppressed this program and restored sensitivity to ICT. These findings reveal an adaptive mechanism of resistance to ICT in RMC and support targeting master myeloid regulators to enable therapeutic benefit.

MM arising within CGMN poses diagnostic and therapeutic challenges. While molecular and epigenomic profiling supports accurate classification and understanding of disease biology, the role of immunotherapy remains uncertain-marked by reduced efficacy and significant immune-related toxicity. A multidisciplinary approach is essential to guide management and improve outcomes in this rare pediatric malignancy.

P1, N=9, Active, not recruiting, Chinese PLA General Hospital | Recruiting --> Active, not recruiting | N=15 --> 9 | Trial primary completion date: Dec 2025 --> Jun 2026

We present a case of a man in his 70s with metastatic melanoma who experienced progression through sequential treatments including pembrolizumab in combination with the HDAC inhibitor entinostat, and ipilimumab. Transdifferentiation has been observed in a wide range of malignancies, but the molecular mechanisms of this phenomenon are poorly understood. This case provides the first molecularly validated example of melanoma to rhabdomyosarcoma transdifferentiation presenting as spatially segregated metastatic lesions with distinct, unmixed histologies and illustrates a mechanism of resistance to immunotherapy driven by phenotypic plasticity.

P1/2, N=110, Active, not recruiting, Universitair Ziekenhuis Brussel | Phase classification: P1 --> P1/2 | Trial completion date: Nov 2023 --> Nov 2026 | Trial primary completion date: Nov 2023 --> Nov 2026