Yervoy (ipilimumab)

P1, N=18, Not yet recruiting, First Affiliated Hospital of Zhejiang University

P3, N=275, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Apr 2026 --> Apr 2027

P3, N=861, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2027 --> Nov 2028

Histopathological examination following radical nephrectomy with tumor thrombectomy demonstrated a pathological complete response. Diffuse programmed death-ligand 1 expression on pretreatment biopsy may have been associated with a favorable response to nivolumab plus ipilimumab.

No disease progression was observed at 9 months. This case demonstrates the potential efficacy of combination immunotherapy in aggressive metastatic MTSCC.

P1, N=12, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Aug 2026 --> Aug 2027

P2, N=18, Recruiting, Mayo Clinic | Not yet recruiting --> Recruiting

Despite 4 cycles of ipilimumab/nivolumab immunotherapy, the disease progressed, and the patient died 4 months after diagnosis. BNM is a rare melanoma variant, often arising from a pre-existing blue nevus, with aggressive potential and frequent lymph node metastasis. The molecular heterogeneity of BNM and the limited therapeutic options underscore the need for further research into targeted therapies and prognostic biomarkers for this rare melanoma subtype.

P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2027 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2027

Guided by precision oncology targeting both immunogenic profile and cell-cycle dysregulation, the patient was treated with dual immunotherapy (pembrolizumab plus ipilimumab) combined with the CDK4/6 inhibitor palbociclib. To our knowledge, this is the first report demonstrating the efficacy of dual checkpoint blockade plus CDK4/6 inhibition in SMARCA4-UT. This case highlights potential of biomarker-driven therapies to overcome resistance in rare thoracic neoplasms.

The ERAP1 inhibitor GRWD5769 combined with cemiplimab, a PD-1 inhibitor, has shown preliminary promise in overcoming resistance to PD-(L)1 blockade by targeting antigen processing. Another resistance-mitigating strategy is potentially IOS-1002, an antagonist of two immunosuppressive receptors, LILRB1/2 and KIR3DL1, combined with anti-PD-1 pembrolizumab. As well, an update on the recently published DART (NCI/SWOG S1609) study indicates that the classic combination of ipilimumab with nivolumab may benefit even more rare cancers, including gestational trophoblastic neoplasia.

This exploratory analysis has several limitations; however, it suggests that patients with pRCC treated with ipilimumab/nivolumab may derive a benefit in terms of 12-month OS rate, median OS, and ORR compared with SOC, particularly among those with CPS > 1. (Funded by Bristol Myers Squibb grant CA209-499; ClinicalTrials.gov, EUDRACT Number: 2016-000706-12; NCT03075423.).