Iberdomide is an oral cereblon E3 ligase modulator with higher affinity to cereblon than immunomodulatory drugs, leading to improved direct anti-myeloma activity and enhanced immunostimulatory effects. We aimed to evaluate the safety and activity of iberdomide plus low-dose cyclophosphamide and dexamethasone (IberCd) in patients with relapsed and refractory multiple myeloma.

Bevacizumab (Bev) often induces hypertension and proteinuria. Optimal antihypertensive management in this setting remains unclear, and studies comparing angiotensin II receptor blockers (ARBs) and calcium channel blockers (CCBs) are limited. The objective of this study was to compare the effects of the ARB azilsartan and the CCB amlodipine on hypertension and proteinuria.

Programmed cell death 1 (PD-1) inhibitors have been the standard first-line treatment for advanced melanoma; however, their clinical benefit in advanced melanoma predominantly of acral subtype remains unclear.

Head and neck squamous cell carcinoma (HNSCC) is the most common type of tumor originating from the squamous epithelium of the oral cavity, oropharynx, larynx and hypopharynx. There is an urgent need to enhance therapeutic efficacy and ensure the function preservation of HNSCC treatment. This study aimed to evaluate the efficacy and safety of neoadjuvant chemoimmunotherapy with pembrolizumab plus docetaxel and cisplatin in patients with resectable locally advanced HNSCC.

Despite widespread immune profiling in cancer immunotherapy, the antigen-specific responses that drive clinical outcomes remain poorly defined. In a prospective neoadjuvant trial (NCT04013854) of a single-dose anti-PD-1 (nivolumab) in stage III melanoma, we performed antigen-specific profiling of melanoma and viral-specific CD8+ T cells across blood, tumor, and lymph node compartments. Using combinatorial tetramers, we detected melanoma-specific CD8+ T cells in 72% of HLA-A1, -A2, and -A3 patients. These cells displayed distinct phenotypes shaped by tissue and antigen context. Tumor-infiltrating T-bet+ intermediate exhausted CD8+ T cells were strongly associated with pathologic response, while CD39+ terminal exhausted cells marked non-response. T-bet and CD39 expression also stratified responses in uninvolved lymph nodes, suggesting early divergence of therapeutic immune trajectories. Longitudinal profiling revealed that circulating melanoma-specific CD8+ T cell dynamics was antigen-dependent and associated with clinical outcomes. Our findings highlight the clinical value of antigen-specific profiling and identify mechanistic correlates of anti-PD-1 efficacy.

QUALIOR-phase 2 multicenter trial explored the feasibility of a home-based supervised physical exercise program (SPEP) in metastatic cancer patients receiving oral targeted therapies.

Protein kinase B (AKT)-directed therapies offer promise for patients with cancers harboring germline and somatic phosphatase and tensin homolog (PTEN) mutations. TAS-117 is an oral, selective, non-adenosine triphosphate-competitive allosteric AKT inhibitor that showed encouraging antitumor activity in a phase I study. This phase II study aimed to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of TAS-117 in patients with advanced/metastatic solid tumors, including those harboring germline PTEN-inactivating mutations (EudraCT: 2020-004770-22).

Fibroblast activation protein (FAP)-targeted radiopharmaceuticals show promise in cancer imaging, but optimization and development of new radiopharmaceuticals to enhance tumor targeting, prolong retention, and improve diagnostic/therapeutic outcomes are ongoing. This study aims to evaluate the biodistribution, pharmacokinetics, dosimetry, and safety of a novel FAP-targeted probe 68 Ga-FAP-75 in humans, and to preliminarily assess its ability to detect malignant tumors.

In the phase 3 KEYNOTE-042 China study of participants enrolled in China in the global KEYNOTE-042 (NCT02220894) and China extension (NCT03850444) studies, pembrolizumab improved overall survival (OS) versus chemotherapy in locally advanced or metastatic non-small-cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% (hazard ratio [HR], 0.63; 95% CI, 0.43-0.94), ≥20% (0.66; 0.47-0.92), and ≥1% (0.67; 0.50-0.89). We present outcomes from this study after 5 years of follow-up. Chinese participants with previously untreated locally advanced or metastatic NSCLC with PD-L1 TPS ≥1% without EGFR or ALK alterations were eligible. Participants were randomized 1:1 to pembrolizumab 200 mg every 3 weeks for up to 35 cycles or carboplatin plus paclitaxel or pemetrexed with optional pemetrexed maintenance (nonsquamous only). Primary endpoints were OS in the PD-L1 TPS ≥50%, ≥20%, and ≥1% subgroups. Median follow-up was 63.7 (range, 56.3-72.6) months among 262 participants (pembrolizumab, n = 128; chemotherapy, n = 134) included in this study. Pembrolizumab prolonged OS versus chemotherapy in participants with PD-L1 TPS ≥50% (HR, 0.65; 95% CI, 0.45-0.93), ≥20% (0.67; 0.49-0.91), and ≥1% (0.66; 0.51-0.87). Grade 3 to 5 treatment-related AEs occurred in 19.5% and 68.8% of participants in the pembrolizumab and chemotherapy groups, respectively. In conclusion, after 5 years of follow-up, pembrolizumab continued to demonstrate improved OS versus chemotherapy with manageable safety in Chinese participants with previously untreated locally advanced or metastatic NSCLC that expressed PD-L1. These data further support pembrolizumab monotherapy as a standard of care for these patients.

Despite the increasing availability of systemic therapies to treat advanced hepatocellular carcinoma (HCC), the prognosis remains poor. There is therefore an unmet need for targeted therapies with a novel mode of action that are more tolerable and effective than current treatment options. Targeted α-therapies selectively deliver high-energy α-particle-emitting radionuclides to tumor-associated cell surface antigens, inducing difficult-to-repair DNA double-stranded breaks, while limiting damage to surrounding tissue. Elevated expression of the oncofetal cell surface heparan sulfate proteoglycan, glypican-3 (GPC3), is seen in more than 70% of HCCs and is a negative prognostic indicator. BAY 3547926 (225Ac-GPC3) is an 225Ac-labeled antibody-chelator conjugate (ACC) that delivers 225Ac directly to GPC3-expressing cancer cells and is a potential first-in-class targeted α-therapy in advanced HCC. Methods: This multicenter, open-label, nonrandomized first-in-human phase 1 dose escalation and expansion study aims to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of 225Ac-GPC3 ACC, with or without preinjection of the nonradioactive GPC3 ACC, in participants with advanced HCC. The study has 3 parts: dose escalation, dose expansion as monotherapy, and safety run-in and dose expansion in combination with standard of care. Key eligibility criteria include diagnosis of locally advanced or metastatic and/or unresectable HCC, with disease not amenable to, or progressive disease after, curative surgery and/or locoregional therapies. To ensure only participants who are good candidates to benefit from 225Ac-GPC3 ACC enter the study, participants will be prospectively screened to confirm GPC3 membrane expression in a tumor specimen. All participants will receive study treatment on day 1 of a 6-wk cycle; additionally, participants in part 3 will receive standard-of-care treatment at the usual frequency. Participants will receive up to 4 doses of the study intervention, unless withdrawn from the study on disease progression, unacceptable toxicity, or fulfillment of any other withdrawal criteria. Primary endpoints include assessment of the occurrence and severity of treatment-emergent adverse events, recommended dose, objective response rate, disease control rate, duration of response, and progression-free survival. Conclusion: Study recruitment commenced in March 2025, and approximately 148 participants will be enrolled. The study will provide important preliminary insights on the efficacy and safety of 225Ac-GPC3 ACC therapy.

Lung cancer (LC) is a prevalent and lethal malignancy with limited treatments for advanced stages. The aim was to investigate the outcome of prophylactic adoption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in advanced LC patients on the basis of concurrent chemoradiotherapy.

Medullary thyroid cancer (MTC) accounts for approximately 4% of thyroid carcinomas. Patients with unresectable, metastatic disease are candidates for approved agent-targeted therapies such as vandetanib, cabozantinib, or selpercatinib, but toxicity is often an issue. Preclinical data supported the potential use of immunotherapy targeting carcinoembryonic antigen (CEA) in this indolent disease.

Anitens are a family of oral N-terminal domain inhibitors of the androgen receptor (AR). In prostate cancer, they may help overcome AR resistance mechanisms at the ligand-binding domain, which is the binding site of approved androgen receptor pathway inhibitors like enzalutamide. Masofaniten (EPI-7386) is a next-generation aniten with promising activity and safety in patients with metastatic castrate-resistant prostate cancer (mCRPC).

Conventional open surgery (OP) is effective and simple for treating papillary thyroid cancer (PTC), but the excessive separation of band strap muscles causes discomfort in the anterior cervical region and a long scar, which may impair the patient's life quality and beauty. Gasless endoscopic surgery via subclavicular approach (ESSA) may provide a better alternative.

To assess efficacy and safety in subgroups of patients treated with Melphalan/Hepatic Delivery System (melphalan/HDS), a drug/device combination for liver-directed treatment of metastatic UM (mUM) patients. Previously reported FOCUS study results indicated melphalan/HDS treatment provides a clinically meaningful response rate and favorable benefit-risk ratio in patients with unresectable mUM.

Ta low-grade bladder tumors, accounting for 45% of new bladder cancer cases, have considerable risk of recurrence but low risk of progression. Traditionally, treatment is burdensome and costly. Office-based laser coagulation of Ta low-grade bladder tumors is efficient, tolerable, and safe; however, long-term outcomes need to be determined. The primary objective of this study was to determine whether in-office laser coagulation of recurrent Ta low-grade bladder tumor is noninferior to standard transurethral resection of bladder tumor (TUR-BT) regarding 12-month recurrence-free survival (RFS).

Most patients with early-stage classical Hodgkin lymphoma (cHL) are treated with doxorubicin, bleomycin, vinblastine, and dacarbazine with or without radiation therapy, although studies are now evaluating the incorporation of novel agents paired with abbreviated chemotherapy. We present the efficacy and safety of AN+AD (brentuximab vedotin [BV] and nivolumab in combination with doxorubicin and dacarbazine) in patients with early-stage cHL. In this phase 2 study, patients with nonbulky (<10 cm) Ann Arbor stage I or II cHL received 4 cycles of AN+AD. The primary end point was complete response (CR) rate at end of treatment (EOT) by investigator. At the time of this analysis, 154 patients received ≥1 dose of AN+AD. The objective response rate at EOT was 96% (95% confidence interval [CI], 91.7-98.6), and the CR rate was 92% (95% CI, 86.0-95.4). In the favorable (n = 56) and unfavorable (n = 97) subgroups, CR rates were 95% (95% CI, 85.1-98.9) and 91% (95% CI, 83.1-95.7), respectively. The proportion of patients with duration of CR of at least 2 years was 96% (95% CI, 90.9-98.4). At a median follow-up of 27.9 months, the estimated 2-year progression-free survival rate was 97% (95% CI, 92.0-98.8). Any-grade and grade ≥3 treatment-emergent adverse events occurred in 99% and 44% of patients, respectively; no events of febrile neutropenia were reported. Any-grade treatment-emergent immune-mediated adverse events occurred in 22% of patients. One disease-related death was reported after the safety reporting period. Results from this study support the use of BV and nivolumab in combination with limited chemotherapy for patients with nonbulky, early-stage cHL. This trial was registered at www.clinicaltrials.gov as NCT03646123.

Up to 20% of patients with cholangiocarcinoma (CCA) harbor FGFR gene aberrations. Erdafitinib is approved for pretreated, locally advanced/metastatic urothelial carcinoma with susceptible FGFR3 alterations. The present study evaluated the efficacy and safety of erdafitinib using a pooled analysis of patients with CCA from the RAGNAR and LUC2001 studies.

This single-center, open-label, single-arm phase II trial (NCT05165407) aimed to evaluate the efficacy and safety of surufatinib (250 mg orally once daily) combined with sintilimab (200 mg intravenously every 3 weeks) and IBI310 (1 mg/kg intravenously every 6 weeks) in patients with advanced high-grade neuroendocrine neoplasms (HG-NENs). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. As of March 28, 2025, 24 patients with measurable baseline lesions and at least one post-treatment tumor assessment were included in the efficacy-evaluable analysis set. The ORR was 37.5% (95% confidence interval [CI]: 18.8-59.4); DCR, 79.2% (95% CI: 57.8-92.9); and median DoR, 14.8 months. Among 31 treated patients in the full analysis set population, the median PFS was 3.81 months (95% CI: 2.79-4.50), and the median OS was 13.44 months (95% CI: 10.28-not estimable). Subgroup analyses showed improved response in patients with the following characteristics: female sex, age <55 years, ECOG performance status of 1, received ≤1 prior treatment line, without liver metastases, and <2 metastatic sites. Treatment-related adverse events (TRAEs) occurred in 96.8% of patients; 45.2% experienced grade ≥3 TRAEs. Among them, 71.0% experienced TRAEs attributed to sintilimab/IBI310, and 87.1% to surufatinib. Serious adverse events occurred in 45.2% of patients. These findings suggest that surufatinib, IBI310, and sintilimab may offer clinical benefit with manageable toxicity in patients with advanced HG-NENs.

Mutant KRAS (mtKRAS) tumors are highly immunosuppressive, largely through secretion of IL-10 and TGF-β2, which prevent immune cell infiltration. Nerofe (dTCApFs), a peptide derivative of Tumor Cell Apoptosis Factor, induces endoplasmic reticulum stress and modulates immune signaling through the T1/ST2 receptor, which is overexpressed in mtKRAS tumors. We evaluated whether combining Nerofe with low-dose doxorubicin (ldDox) could remodel the immune microenvironment and overcome tumor immunosuppression.