APX3330 is an oral agent targeting the redox signaling activity of APE1/Ref-1 (Ref-1), a key regulator of transcription factors involved in inflammation and tumorigenesis. APX3330 selectively inhibits Ref-1's redox function without affecting its DNA repair role. This Phase 1, multicenter, open-label, dose-escalation study in advanced solid tumors was aimed at determining the recommended Phase 2 dose (RP2D) while assessing safety, pharmacokinetics, and biomarker evidence of target engagement.

Programmed cell death protein-1 inhibitors have improved metastatic non-small cell lung cancer (NSCLC) prognosis. Stereotactic ablative body radiation therapy (SABR) may enhance immunity. This study evaluated the activity and safety of adding SABR to first-line immunotherapy post chemotherapy with nivolumab for metastatic NSCLC.

Paclitaxel-induced peripheral neuropathy (PIPN) is a dose-limiting adverse effect during paclitaxel therapy, with no effective treatment and often incomplete recovery. This study assessed the effects of exercise on PIPN severity in newly diagnosed advanced breast cancer patients.

To compare the efficacy and safety of brolucizumab 6 mg and aflibercept 2 mg in patients with neovascular age-related macular degeneration (nAMD) using an identical 4-week adjustment Treat-and-Extend regimen.

Accurate diagnosis of oral mucositis (OM) is essential for effective management and plays a critical role in ensuring reliable outcomes in clinical trials evaluating OM-prevention and treatment strategies. Currently, no evidence-based guidelines specify which clinical profession should be primarily responsible for OM assessments in patients undergoing high-dose chemotherapy. In most Scandinavian countries, nurses perform daily OM assessments, while dentists specialized in orofacial medicine (considered the gold standard) conduct supplementary evaluations several times per week. However, the concordance between nurses' assessments and those conducted by dentists specialized in orofacial medicine remains unclear. Therefore, this study aimed to evaluate the interrater reliability in of OM assessments between these two professions.

AC699 is a novel, orally bioavailable chimeric estrogen receptor-α (ERα) degrader that induces proteasome-dependent ERα degradation via cereblon E3 ligase recruitment. Here we report findings from a first-in-human, phase 1, dose-escalation study of once-daily AC699 (100-600 mg) in patients with heavily-pretreated, locally-advanced/metastatic ER-positive/HER2-negative breast cancer (ClinicalTrials.gov Identifier: NCT05654532). Primary objectives are to assess dose-limiting toxicities and treatment-emergent adverse events (TEAEs). Secondary objectives are to evaluate pharmacokinetics, objective response rate (ORR), clinical benefit rate (CBR, including stable disease ≥24 weeks), duration of response (DOR), and progression-free survival (PFS). Among 37 treated patients, TEAEs occurred in 78% of patients, most commonly nausea (19%), fatigue (16%), and neutropenia (16%). All treatment-related adverse events were Grade 1/2, with no dose reductions/discontinuations; the maximum tolerated dose was not reached. Of 26 efficacy-evaluable patients, 4 (15%) achieved partial responses and CBR was 23%. In exploratory analysis of patients with ESR1 mutations, ORR and CBR were 40% and 45%, respectively. Median DOR and PFS were 6.5 and 3.6 months overall, and 6.5 and 7.4 months in ESR1-mutant patients. AC699 steady-state exposure increased approximately dose-proportionally between 100-400 mg, plateauing at 600 mg. AC699 demonstrated favorable safety, predictable PK, and encouraging antitumor activity, particularly in ESR1-mutant disease.

Neutralization of interferon (IFN)-γ abrogates the efficacy of anti-programmed death-ligand 1 (PD-(L)1) checkpoint inhibitors. Most epithelial cells do not constitutively express major histocompatibility complex (MHC) class II but can be induced to do so by IFN-γ. Inducible tumor-specific MHC class II (tsMHC-II) underlies responsiveness to anti-PD-(L)1. Retrospective studies show that tsMHC-II positivity associates with improved outcomes in patients treated with anti-PD-(L)1. The ANICCA-Class II single-arm Bayesian phase II trial prospectively explored whether positive tsMHC-II status could be a useful selection marker for anti-programmed cell death protein-1 (PD-1) in proficient mismatch repair colorectal cancer (pMMR CRC). In parallel, we retrospectively evaluated the potential predictive power of immunoscore-immune checkpoint (IS-IC) for outcome with single-agent immune checkpoint blockade.

Liquid biopsies hold promise to improve the diagnosis, assessment of response to therapy, and ultimately guide the management of cancer patients. However, implementation of this approach in brain tumors has proven challenging due to the limited passage of molecules across the blood-brain barrier (BBB). We recently reported results from a phase I clinical trial in which the BBB was transiently opened in glioblastoma (GBM) patients using skull-implantable low-intensity pulsed ultrasound combined with microbubbles (LIPU/MB). In this study, treatment and BBB opening was performed every 3 weeks with paclitaxel administration until disease progression or up to 6 cycles (NCT04528680). As an exploratory objective of this trial, here we investigate extracellular vesicles and particles (EVPs/EPs) released into circulation in the context of tumor cell death as a potential biomarker for response to treatment. We develop and validate a microfluidic device designed to capture tumor-derived EVPs in glioblastoma patients (GlioExoChip). This approach leverages GBM-based expression of phosphatidylserine and Annexin-V chemistry that is traditionally used to measure apoptosis. EVPs are characterized using nanoparticle tracking analysis, proteomics, western blot, and scanning electron microscopy. Proteomic analysis of circulating EVPs isolated from GBM patients reveals distinct expression patterns to that of healthy individuals, and scRNA-seq analysis of these genes supported their tumoral origin within the GBM microenvironment. In vitro, paclitaxel-susceptible glioma cells treated with this drug exhibit apoptosis and dose-dependent EVP release. In concordance, we find changes in EVP release following the initiation of paclitaxel with LIPU/MB correlated with overall survival in GBM patients. Thus, our study introduces an efficient microfluidic platform for the capture of circulating GBM EVPs and demonstrates that release upon BBB opening is predictive of outcomes following paclitaxel treatment. This approach represents a real-time surrogate biomarker for treatment response for a disease where imaging-based assessment of response has not been shown to be reliable. Future prospective validation is warranted.

Immune checkpoint inhibitors (ICIs) have improved survival in advanced non-small cell lung cancer (NSCLC), yet resistance remains a major challenge. Here, we report the results from cohort A of a multi-cohort, phase II, open-label trial [NCT04777084], evaluating the efficacy and safety of IBI318 (a bispecific anti-PD-1/PD-L1 antibody, 300 mg intravenous every 2 weeks) plus lenvatinib (a receptor tyrosine kinase inhibitor, 8 mg orally daily). Forty patients with advanced NSCLC and acquired resistance to first-line ICIs were enrolled and received at least 1 cycle of the study regimen. The primary endpoint of 12-week objective response rate was 40.0% (95% CI: 24.9-56.7), satisfying prespecified efficacy threshold. Secondary endpoints included other efficacy endpoints and safety. Median progression-free and overall survival were 6.9 months (95% CI: 4.8-9.5) and 18.2 months (95% CI: 10.7-29.1), respectively. The most common treatment-related adverse event was increased thyroid-stimulating hormone (n = 11). Grade ≥3 adverse events occurred in 12.5% (5/40) of patients. Further, we performed a post-hoc exploratory analysis and developed an XGBoost model (scPro-X) using scRNA-seq data from pre-treatment tumor samples to predict 12-week ORR identified CD4_Tfh_CXCL13 and CD8_Tex_CTLA4 as potential biomarkers predictive of response. These findings demonstrate that IBI318 plus lenvatinib exhibit promising clinical activity and a manageable safety profile in patients with advanced NSCLC.

To observe the clinical efficacy of herb-spreading moxibustion as an adjuvant treatment for chemotherapy-induced nausea and vomiting (CINV) of spleen and stomach deficiency cold in gastric cancer.

Many patients receiving frontline tyrosine kinase inhibitors (TKIs) for chronic-phase chronic myeloid leukemia (CML-CP) experience inadequate disease control and/or adverse events (AEs) that impair quality of life. Treatments offering optimal efficacy, safety, and tolerability will support long-term therapy. In the primary analysis from the ASC4FIRST trial, a phase 3 randomized trial comparing asciminib with investigator-selected TKIs (IS-TKIs) in newly diagnosed CML-CP, asciminib demonstrated superior efficacy vs all IS-TKIs and vs imatinib in the imatinib stratum, meeting both primary objectives. In the secondary analysis (2.2 years' median follow-up), major molecular response (MMR) rate at week 96 was 74.1% with asciminib vs 52.0% with IS-TKIs (treatment difference, 22.4% [95% confidence interval (CI), 13.6-31.3]; 1-sided P< .001) and 76.2% with asciminib vs 47.1% with imatinib in the imatinib stratum (treatment difference, 29.7% [95% CI, 17.6-41.8]; 1-sided P< .001), meeting both key secondary objectives. MMR rate was 72.0% with asciminib vs 56.9% with second-generation (2G) TKIs (treatment difference, 15.1% [95% CI, 2.3-28.0]; 1-sided P< .05), suggesting possible clinical benefit, although the study was not designed to formally confirm statistical significance for this secondary end point. Safety/tolerability remained favorable with asciminib vs IS-TKIs. Dose reductions and interruptions, respectively, occurred with asciminib (18.5%; 46.5%), imatinib (23.2%; 47.5%), and 2G TKIs (54.9%; 63.7%). The hazard ratio for time to discontinuation of treatment due to AEs for asciminib vs 2G TKIs was 0.46 (95% CI, 0.215-0.997). With longer follow-up, asciminib continued to demonstrate a favorable benefit-risk profile over IS-TKIs and imatinib, supporting its potential as a treatment option for newly diagnosed CML-CP. This trial was registered at www.clinicaltrials.gov as NCT04971226.

To study the efficacy of brolucizumab in chronic central serous chorioretinopathy (CSCR) with persistent fluid without choroidal neovascular membrane (CNVM).

Gastrointestinal (GI) malignancies are major contributors to global cancer-related mortality, with many patients experiencing severe nutritional decline and immune suppression due to chemotherapy. Enteral immunonutrition (EIN), which includes immune-modulating nutrients, has shown promise in improving nutrition, reducing chemotherapy-related side effects, and enhancing immune function, but its role in advanced GI cancer patients undergoing chemotherapy is not well-studied.

E7386 is an orally active inhibitor reported to block the CBP/β-catenin interaction. We present data from the dose-escalation and expansion part 1 of Study 103 (phase I) of E7386 in patients with advanced, unresectable, or recurrent (A/U/R) solid tumors.

Docetaxel is a first-line chemotherapy drug for breast cancer and is traditionally dosed based on body surface area (BSA). However, this method often leads to significant inter-patient variability and a high incidence of adverse drug reactions (ADRs). Therapeutic drug monitoring (TDM) offers a personalized dosing approach that may improve drug safety and efficacy. This study aimed to evaluate the clinical and pharmacoeconomic benefits of TDM-guided dosing compared to traditional BSA-based dosing in breast cancer patients receiving docetaxel-based chemotherapy.

Richter transformation is one of the most challenging B-cell lymphomas to treat, particularly in patients with high-risk chronic lymphocytic leukaemia features or who have had previous therapy for chronic lymphocytic leukaemia. Median survival remains 6-12 months across various therapeutic approaches. We evaluated the safety and preliminary activity of epcoritamab monotherapy, a subcutaneous CD3×CD20 bispecific antibody, in patients with Richter transformation.

Talazoparib is a poly(ADP-ribose) polymerase inhibitor approved for the treatment of breast and prostate cancer. Commercialization of a soft gelatin capsule (SGC) formulation developed post-approval required a bioequivalence (BE) and food effect (FE) study to bridge SGC with the initial commercial hard capsule (HC) formulation. Study execution and meeting BE criteria are challenging due to high variability in Cmax, potentially higher Cmax for SGC based on dissolution data, and the need to perform BE/FE assessment at steady state in cancer patients. Model-informed drug development (MIDD) was used to facilitate an efficient/feasible study design. Semi-mechanistic pharmacokinetic (PK)/pharmacodynamic (PD) modeling and simulations showed that AUC, instead of Cmax, drove hematologic events, the main side effects of talazoparib. This supported a BE study powered for AUC equivalence only. Population PK simulation showed that following a 28-day treatment in the first period, 14 days in subsequent periods is sufficient for steady-state BE/FE assessments. Study results showed AUC met BE criteria while Cmax was 37% higher for SGC relative to HC, which was deemed not clinically significant based on the PK/PD model. FE on SGC formulation was consistent with FE on HC formulation reported previously. The safety profile of the two formulations was generally consistent with the known safety profile. The totality of data (AUC equivalence, lack of impact of Cmax on safety, observed safety data) supported bridging of the two formulations although Cmax failed to meet BE criteria. MIDD was critical in study design optimization and supported approval of the SGC formulation. Trial Registration: ClinicalTrials.gov Identifier: NCT04672460.

Breast cancer treatment is associated with cancer-related cognitive impairment (CRCI). However, the association of endocrine therapy (ET) vs chemotherapy plus endocrine therapy (CET) with CRCI is poorly understood.

Chemotherapy-induced diarrhea is a common and distressing side effect experienced by patients undergoing cancer treatment, particularly those with gastrointestinal cancer. It can lead to significant health complications, including dehydration, electrolyte imbalances, and treatment interruptions. Recent studies have shown that the gut microbiome plays an important role in the development and severity of chemotherapy-induced diarrhea. Modulating the gut microbiome with probiotics has emerged as a potential strategy for preventing and managing chemotherapy-induced diarrhea.

Immunotherapeutic strategies combining Immune checkpoint blockade (ICB) and therapeutic T-cell vaccination hold promise to enhance HIV-1 remission in people with HIV (PWH). While T-cell vaccination alone has shown limited efficacy, ICB may potentiate vaccine-induced T-cell responses. We investigate the functional impact of ICB on vaccine-induced HIV-1-specific CD8+ T-cell responses using relevant samples from PWH receiving early ART and T-cell vaccination.