Keytruda (pembrolizumab)

P1/2, N=50, Active, not recruiting, University of Cincinnati | Trial completion date: Sep 2025 --> Sep 2026

A 77-year-old woman with stage IV serous endometrial carcinoma presented 24 days after a single dose of carboplatin, paclitaxel, and pembrolizumab, with progressive weakness, ptosis, diplopia, and respiratory compromise...She was treated with pulse corticosteroids and plasma exchange (PLEX), with rituximab added after the second session for an inadequate response. Persistent myocarditis with sustained troponin elevation prompted further escalation to abatacept and ruxolitinib...The case is distinguished by refractory disease requiring four sequential lines of immunosuppression, concurrent immune-mediated hepatitis and thyroiditis, and a seronegative myasthenia gravis profile, consistent with the more heterogeneous, non-antibody-mediated mechanisms increasingly recognized in ICI-induced disease. It informs treatment escalation in refractory cases and underscores three principles essential to managing this high-mortality syndrome: early recognition, systematic screening for all syndromic components once any one is identified, and timely escalation through multiple lines of immunosuppression when disease proves refractory.

Adjuvant immunotherapy has transformed the management of high-risk resected ccRCC, with pembrolizumab demonstrating improvements in DFS and OS...Additional biomarkers including sarcomatoid differentiation, specific genomic drivers (PBRM1, BAP1, VHL), circulating tumor DNA, epigenetic signatures, and systemic inflammatory markers, provide complementary insights into tumor biology and host-tumor interaction. Although none of these biomarkers are currently validated for routine clinical decision-making, integrative models combining clinicopathologic and molecular features may enable more precise selection of patients for adjuvant immunotherapy and help reduce overtreatment in localized ccRCC.

P2, N=70, Active, not recruiting, University of Southern California | N=103 --> 70 | Trial completion date: Nov 2026 --> Dec 2030 | Trial primary completion date: Nov 2025 --> Dec 2027

P2, N=62, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Initiation date: May 2026 --> Jan 2027

P4, N=110, Not yet recruiting, Centre Antoine Lacassagne

We report the case of a 26-year-old man with a primary mediastinal yolk sac tumor who progressed despite multimodal therapy, including etoposide, ifosfamide, and cisplatin chemotherapy, high-dose carboplatin and etoposide with autologous stem cell transplantation, gemcitabine and paclitaxel, surgical debulking, and radiation therapy. No further disease-directed therapies were available, and he ultimately died from progressive metastatic disease. This case highlights the aggressive biology of platinum-resistant primary mediastinal yolk sac tumors, illustrates primary resistance to programmed death-1 inhibition, and underscores the urgent need for more effective salvage strategies in this high-risk population.

Recent phase III data have led to approval of perioperative pembrolizumab for patients with PD-L1-positive (CPS ≥ 1)...In addition, potential strategies to optimize treatment efficacy and to overcome resistance mechanisms of CPI therapy are discussed. Further trials are needed to define optimal treatment protocols, determinate the best timing of surgery, and identify reliable biomarkers for patient selection, to guide evidence-based therapeutic decision-making in routine clinical practice.

A 64-year-old man with metachronous metastatic urothelial carcinoma originating from the right renal pelvis underwent nectin-4-targeted [68Ga]Ga-NECT-224 PET/CT prior to initiation of nectin-4-targeted antibody-drug conjugate (ADC) therapy with enfortumab-vedotin (PADCEV), in combination with pembrolizumab. Subsequent [68Ga]Ga-NECT-224 PET/CT restaging revealed multiple new lesions with intense nectin-4 expression. This case illustrates the potential of [68Ga]Ga-NECT-224 PET/CT to visualize heterogeneous nectin-4 expression, its potential in therapy guidance, and highlights the need for theranostic strategies in patients retaining target expression despite cytotoxic therapy resistance.

At 15 months following initiation of therapy, the patient remains on maintenance treatment with bevacizumab and pembrolizumab, with no evidence of disease progression to date. This case highlights the potential efficacy of immune checkpoint inhibitor-containing multimodality treatment regimens in the management of advanced cervical SCNEC.

Lenvatinib was interrupted, and intravenous piperacillin/tazobactam was administered; her symptoms improved without drainage. Lenvatinib was resumed at 8 mg with pembrolizumab, and no recurrence occurred. Early recognition and temporary interruption of lenvatinib with antibiotics may allow cautious rechallenge.

P1/2, N=6, Not yet recruiting, Shanghai 6th People's Hospital