With high-risk neuroblastoma, post-induction metastases in bone marrow (BM)/bones confers a poor prognosis but can respond to anti-GD2 antibody, such as naxitamab. We report results of a phase I/II trial.

Systematic pelvic and aortic lymphadenectomy in stage IIB-IVB patients with epithelial ovarian cancer, undergoing complete abdominal macroscopic resection with normal lymph nodes, was revealed to have no prognostic significance for survival in the LION trial. However, the proportion of patients with ovarian clear cell carcinoma (OCCC) in the LION trial was only 2.2%, so the significance of systematic retroperitoneal lymphadenectomy in patients with OCCC remains unclear.

Translating trial findings to real-world cure rates for resectable oesophageal and gastroesophageal junction (GEJ) adenocarcinoma is critical. Standard endpoints like disease-free survival (DFS) may not distinguish durable cures from delayed recurrences.

Invariant Natural killer T (iNKT) cells exhibit cytotoxic activity and immunomodulatory functions and have gained interest in cancer immunotherapy. We conducted a phase 1, first-in human clinical trial to evaluate the safety and efficacy of clinical-grade allogeneic iNKT cells generated from induced pluripotent stem cells (iPSC-iNKT cells) in patients with recurrent head and neck cancer (jRCT2033200116). The primary endpoint was the incidence of dose-limiting toxicity (DLT). The secondary endpoints were to assess safety and efficacy, as well as to evaluate immunological dynamics. iPSC-iNKT cells were administered intra-arterially to 10 patients. One subject developed grade 3 skin rash at the second dose, identified as DLT. No other severe adverse events were observed in any patients. Tumor progression was suppressed in two patients, in whom clonal expansion of memory- and effector-phenotype CD8+ T cells was observed, along with activation of the IFN-γ signaling pathway. Here, we show that iPSC-iNKT cells are safe and possess therapeutic potential as an immunotherapy for solid tumors.

The NeoRHEA was a single-arm phase 2 study that included patients with estrogen receptor positive / human epidermal factor receptor 2 negative early breast cancer that received 4 cycles of neoadjuvant palbociclib and endocrine therapy. The primary outcome was baseline biomarkers of treatment resistance and secondary outcome was post-treatment transcriptional and epigenetic changes of tumor, immune and stromal cells. E2F targets and G2M checkpoint proliferation-related genes gene sets were enriched in baseline samples from resistant patients., Downregulation of E2F targets and G2M checkpoint post treatment was observed in tumor, endothelial and T cells. Gene Set Enrichment Analyses (GSEA) based on genes residing in the differentially accessible peaks revealed similar effects,. Moreover, decreases in CD8 + CD103+ tissue-resident memory cell marker genes were observed post-treatment and validated by multiplex immunohistochemistry. Our data reveal that treatment with palbociclib and endocrine therapy diminishes adaptive anti-tumor immunity by decreasing T cell proliferation and the presence of tissue-resident memory T cells NCT03065621.

Immune checkpoint inhibitors (ICIs) combined with cytotoxic chemotherapy are now the standard first-line treatment for advanced biliary tract cancer (BTC). With this evolving landscape, therapeutic options using ICIs after first-line failure are urgently needed. Anti-angiogenic agents may enhance anti-tumor immunity by increasing tumor antigen presentation and promoting lymphocyte infiltration and migration. We aimed to evaluate the efficacy of sitravatinib plus tislelizumab as second-line therapy for advanced BTC.

Immune checkpoint inhibitors have transformed the management of triple-negative breast cancer (TNBC) but outcomes could be improved further. We explored combining the T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) inhibitor tiragolumab with atezolizumab-containing regimens for patients with early-stage or advanced TNBC.

In the phase III KEYNOTE-522 study (NCT03036488), which defined triple-negative breast cancers (TNBCs) as tumours with an estrogen receptor (ER) level ≤1% (ER-null) according to European Society for Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) guidelines, the rate of pathological complete response (pCR) was increased by pembrolizumab addition to neoadjuvant chemotherapy. This combination has become the standard of care for stage II or III TNBC. However, updated ASCO guidelines suggest that tumours with low ER levels should be treated as ER-null. In some European countries, tumours with 1%-9% ER expression, called 'ER-low', are considered and treated as ER-null despite a lack of data concerning this population.

The standard of care for advanced cervical cancer includes chemotherapy, antiangiogenic, and/or immune checkpoint blockade regimens. Although effective, it leads to pleiotropic side effects. Deescalation chemotherapy together with immunotargeted therapies has been proven effective and less toxic in other cancers. In this study, we conducted a multicenter, single-arm, phase II study of first-line deescalated platinum-based chemotherapy plus anlotinib and penpulimab, followed by maintenance therapy solely with anlotinib and penpulimab in patients with PD-L1-positive, persistent, recurrent, or metastatic cervical cancer. Of 32 efficacy-evaluable patients, 30 (93.8%, 95% confidence interval, 79.2%-99.2%) had an investigator-confirmed objective response. Single-nucleus RNA sequencing implied enhanced chemotaxis and proliferative activity of tumor-infiltrating T cells, and activated germinal center B cells portended optimal treatment response. Patients with a high tertiary lymphoid structure-to-tumor area ratio exhibited better survival. Our findings lay the groundwork for the feasibility of first-line de-escalated chemotherapy plus anlotinib and penpulimab in patients with metastatic, persistent, or recurrent cervical cancer.

We present the preclinical rationale and clinical data from a phase 1b trial investigating the STING agonist dazostinag plus pembrolizumab following hypofractionated radiotherapy (RT) in patients with advanced non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), or squamous cell carcinoma of the head and neck (SCCHN) whose disease had progressed on prior checkpoint inhibitors (CPI; NCT04879849).

Systemic administration of 5-aminolevulinic acid (5-ALA) results in accumulation of the sonosensitizing compound protoporphyrin IX in tumor cells because of their aberrant metabolism. Activation of protoporphyrin IX by noninvasive, magnetic resonance-guided focused ultrasound (MRgFUS) sonodynamic therapy (SDT) induces production of reactive oxygen species and tumor cytotoxicity. In this first-in-human, open-label, early clinical study (NCT04559685), safety and biological efficacy of ascending doses of MRgFUS combined with intravenous administration of 5-ALA (SONALA-001) were assessed in nine patients with recurrent high-grade glioma. The safety assessment revealed no drug-related or device-related toxicities. Pharmacokinetic analysis provided quantitative information on the concentration of 5-ALA and protoporphyrin IX in plasma, blood, and brain tissue. Comparison of pharmacodynamic markers between half of the tumor region treated with MRgFUS compared with the untreated tumor provided information on dose-related changes in markers of oxidative stress and cell death for each patient's tumor. This early phase clinical trial demonstrates proof of principle for 5-ALA SDT as a therapeutic modality for glioma. Further research is needed to optimize treatment parameters for clinical efficacy and to explore the potential of 5-ALA SDT in other types of cancer.

ROS1 rearrangement is rare but is an attractive therapeutic target in advanced non-small cell lung cancer (NSCLC). Crizotinib, entrectinib, and repotrectinib have been approved by the US Food and Drug Administration for treatment of ROS1-positive NSCLC. Lorlatinib, a brain-penetrant, third-generation tyrosine kinase inhibitor (TKI), targets ROS1 and ALK; however, its efficacy and safety for patients with advanced ROS1-positive remains unknown.

The Gleason grading system for prostate cancer (PCa) is based on the proportions of Gleason patterns (GP) 3-5. While pure GP3 has minimal metastatic potential, it is unclear whether GP3 quantity in the presence of GP4 and GP5 affects oncological outcomes.

Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) exhibit a dismal prognosis, occurring in 44%-62.2% of cases at initial diagnosis. The optimal treatment for this population remains undefined.

Combining neoadjuvant immunotherapy with chemoradiotherapy may improve outcomes in esophageal cancer; however, factors underlying its effectiveness remain unclear. This study evaluated the efficacy of neoadjuvant tislelizumab combined with chemoradiotherapy and investigated changes in immunological indicators to identify individuals who may benefit from neoadjuvant treatment.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here we report the results of a phase II clinical trial (NCT03274258) of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in patients with RMC, with objective response rate as primary outcome. Enrollment was halted for futility at a prespecified interim analysis as all 10 treated patients experienced rapid disease progression. 5/10 met radiological criteria for hyperprogression and median progression-free survival (secondary outcome) was 1.38 months (95% confidence interval: 1.28, 1.60). In a post-hoc single-cell RNA sequencing analysis, data from patients with RMC before and after nivolumab plus ipilimumab treatment indicated that immune checkpoint therapy (ICT) triggered an interferon-γ response that induced a "myeloid mimicry" program in tumor cells, regulated by the CEBPB / p300 axis and linked to proliferation and hyperprogression. In preclinical experiments using an immunocompetent somatic mosaic genetically engineered mouse model of RMC, combination ICT accelerated tumor growth while activating myeloid-affiliated transcriptional circuits. 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.

Relapsed or refractory osteosarcoma carries a poor prognosis after standard chemotherapy. We conducted a multicenter, randomized, phase II trial (NCT05277480) to compare apatinib plus ifosfamide/etoposide (IE) with IE alone in patients who had progressed following at least one prior line of chemotherapy. Patients were randomized 2:1 to receive apatinib (500 mg orally once daily) plus IE (ifosfamide 1.8 g/m²/day and etoposide 100 mg/m²/day, days 1-3 every 3 weeks) or IE alone (same doses, days 1-5 every 3 weeks). The primary endpoint was progression-free survival (PFS). Between April 14, 2022, and August 22, 2023, 81 patients were enrolled (53 in apatinib plus IE group and 28 in IE group). After a median follow-up of 19.9 months, the median PFS was 5.5 months (95% confidence interval [CI]: 3.9, 6.4) with apatinib plus IE compared with 3.4 months (95% CI: 1.4, 4.6) with IE (hazard ratio, 0.60; 95% CI: 0.37, 0.98; P = 0.0402). The trial met its pre-specified primary endpoint. These results suggest that apatinib plus IE may improve PFS in relapsed or refractory osteosarcoma, but as a randomized phase II study, the findings are exploratory and require confirmation in phase III trials.

Prostate cancer (PCa) remains a major clinical challenge due to limited treatment efficacy, frequent resistance, and high recurrence rates. Given the susceptibility of cancer cells to oxidative stress, reactive oxygen species (ROS)-based strategies offer promising therapeutic potential. Photothermal therapy (PTT) and sonodynamic therapy (SDT) are emerging minimally invasive modalities that exploit nanotechnology to induce localized ROS generation. This review highlights recent advances in ROS-mediated PTT and SDT for PCa, emphasizing nanomaterial design and functionalization to enhance targeting precision, drug delivery, and overcome tumor hypoxia. Combining PTT and SDT with chemotherapy, radiotherapy, or immunotherapy produces synergistic effects, potentially overcoming resistance and eliciting systemic antitumor immunity. Preclinical studies demonstrate effective tumor eradication and immune activation with minimal toxicity, suggesting promise for clinical translation. However, human clinical trials remain scarce, and further translational research is needed before these nanotechnology-based approaches can be integrated into standard PCa treatment.

To evaluate the efficacy and safety of the bispecific human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate (ADC) TQB2102 in the neoadjuvant treatment of HER2-positive breast cancer.

This phase 2 study evaluated the efficacy and safety of combining acalabrutinib and lenalidomide with either rituximab (ALR) or obinutuzumab (ALO), with longitudinal minimal residual disease (MRD) monitoring in frontline MCL treatment. The primary objective was molecular complete response (CR) after 12 cycles of induction, defined by Lugano criteria, and undetectable MRD of <10-6 (uMRD6) by clonoSEQ. Secondary objectives included safety, responses, and survival. Exploratory objectives included tumor mutation profiles and cell-free DNA (cfDNA) by cancer personalized profiling by deep sequencing. Patients in uMRD6 molecular CR were eligible for discontinuation of acalabrutinib plus lenalidomide after 24 cycles; all patients received a minimum of 36 cycles of anti-CD20 antibody treatment. In the ALR cohort, grade 3/4 hematologic toxicities included neutropenia (38%), thrombocytopenia (4%), and anemia (4%). Nonhematologic toxicities included rash (42%), fatigue (4%), nausea (4%), and vomiting (4%). The overall response rate (ORR) was 100%, CR rate was 83%, and molecular CR rate was 67% after 12 cycles of induction, with best molecular CR at 83%. At a median follow-up of 53 months (range, 46-60), the 4-year overall survival (OS) and progression-free survival (PFS) for ALR were 91% and 76%, respectively. TP53 mutations were adversely associated with PFS (P = .026). For ALO, ORR, CR, and molecular CR were 90% after induction, and 2-year OS and PFS were both at 100%. Longitudinal cfDNA analysis in ALR revealed clonal evolution during response and progression. This safe and active regimen is feasible as a time-limited initial therapy for patients with MCL and warrants further evaluation in response-adapted strategy. This trial was registered at www.ClinicalTrials.gov as NCT03863184.