CheckMate 915 (NCT03068455) compared adjuvant nivolumab monotherapy versus combination nivolumab+ipilimumab in patients with resected stage III/IV melanoma. This exploratory analysis was performed to identify biomarkers that correlate with benefit from adjuvant immunotherapy.

This study aims to compare the safety and efficiency of modified biweekly CAPOX and conventional triweekly CAPOX in high-risk stage II and stage III post-surgery colorectal (CRC) patients.

Biomarker-enriched, chemotherapy-free treatments for patients with advanced gastric and gastroesophageal junction cancer have not been widely explored. In this multicenter, phase 2 trial (NCT04363801), we evaluated the efficacy and safety of second-line doublet immunotherapy, combining DKN-01, an immunomodulating antibody targeting Dickkopf-related protein 1 (DKK1), with the anti-programmed cell death-1 (PD1) antibody, tislelizumab in patients with advanced gastric/gastroesophageal junction cancer and elevated tumor DKK1 expression, a putative predictive biomarker for DKN-01. Here we report part B (second line cohort) of the larger DisTinGuish trial. The primary endpoint was safety and tolerability, with secondary endpoints including objective response rate (ORR), overall survival (OS), progression free survival (PFS), and disease control rate (DCR). The trial met the prespecified primary endpoint. In the safety population (n = 52), 21 (40.4%) patients reported at least 1 DKN-01-related adverse event, most of which were low-grade, with fatigue (15.4%) and nausea (9.6%) being most common. The ORR was 21.7% in the overall population (n = 46) and 31.8% in the programmed death-ligand 1 (PD-L1) ≥ 5% population. The median OS was 8.2 months, median PFS 1.4 months, and DCR rate 34.8% in the overall population. Although exploratory, the results of this trial compare favorably against second-line benchmarks of Keynote-061 and RAINBOW and support the safety and tolerability of DKN-01 combined with tislelizumab.

Gut microbiota modulation is an emerging strategy to improve cancer therapy outcomes. This study evaluated the safety and therapeutic potential of combining oral vancomycin-a non-absorbed, gut-restricted antibiotic with primary activity against gram-positive bacteria-with stereotactic body radiotherapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). The underlying hypothesis was that vancomycin-induced changes in gut microbiota could enhance the antitumor effects of SBRT.

To evaluate the clinical efficacy of evidence-based Enhanced Recovery After Surgery (ERAS) nursing protocols in patients undergoing robotic-assisted partial nephrectomy using the Da Vinci system.

Talquetamab is the first approved G protein-coupled receptor family C group 5 member D-targeting bispecific antibody for the treatment of triple-class exposed relapsed/refractory multiple myeloma (RRMM) on the basis of results from the phase 1/2 MonumenTAL-1 study (ClinicalTrials.gov identifiers NCT03399799 and NCT04634552). This study describes patient-reported outcomes (PROs) among patients who received talquetamab in MonumenTAL-1.

Immune checkpoint receptor lymphocyte-activation gene 3 (LAG-3) is an activation marker for CD4+ and CD8+ T cells. Prolonged LAG-3 expression downregulates T-cell activation; therefore, LAG-3 blockade may restore antitumor immune response. INCAGN02385 is a humanized monoclonal LAG-3-targeting antibody. This first-in-human phase I study evaluated INCAGN02385 for advanced/metastatic solid tumors.

T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is an immune checkpoint receptor upregulated during anti-programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy for cancer. TIM-3 blockade may improve the antitumor activity of PD-1/PD-L1inhibition. This phase 1 study evaluated INCAGN02390, a novel, fully human Fc-engineered antibody against TIM-3.

Immune checkpoint inhibitors in combination with chemotherapy have been a common first-line treatment for non-small cell lung cancer (NSCLC), but they do not work for all patients. HDAC inhibitors (HDACis) may synergize with progressive disease (PD)-1 antibodies by inducing and activating cellular immunity. In this phase II study, we assessed the efficacy and tolerability of chidamide and tislelizumab in combination with chemotherapy in NSCLC patients.

This trial (KLASS-12) compares the efficacy and safety of reduced-port laparoscopic gastrectomy (RPLG) versus conventional 5-port laparoscopic gastrectomy (CPLG) for early gastric cancer (EGC).

Angiogenesis is critical in intrahepatic cholangiocarcinoma (ICC), a highly lethal cancer with limited treatment options. Sunitinib, a multi-receptor tyrosine kinase inhibitor, has strong antiangiogenic and antitumor effects. We aimed to evaluate the efficacy and tolerability of sunitinib as a second-line treatment in chemotherapy-pretreated patients with advanced ICC.

Capivasertib is a potent, selective pan-AKT inhibitor. In the Phase III CAPItello-291 trial in patients with aromatase inhibitor-resistant, hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, the addition of capivasertib (400 mg twice daily, 4 days on, 3 days off) to fulvestrant significantly improved the dual primary endpoints of progression-free survival in the overall and PIK3CA/AKT1/PTEN-altered population compared with placebo plus fulvestrant and had an acceptable safety profile. Based on data from six Phase I-III trials (N = 851), a three-compartment population pharmacokinetic model was used to generate individual Bayes' capivasertib steady-state exposure parameters (AUC, Cmax, and Cmin). No relationship between exposure and efficacy (progression-free survival or objective response rate) was identified in CAPItello-291 (n = 394). The safety analysis, which pooled data from CAPItello-291 and a Phase I trial (n = 468), identified significant relationships between capivasertib exposure and the likelihood of an adverse event (AE) leading to dose modification, AE grade ≥ 3, and diarrhea AE grade ≥ 2; whereas, no significant relationships were identified between capivasertib exposure and AE leading to dose discontinuation, serious AE, AE grade ≥ 1, rash AE grade ≥ 2, hyperglycemia AE grade ≥ 1, hyperglycemia AE grade ≥ 3, or increased blood glucose > 13.9 mmol/L. These results support the consistent benefit observed with the intermittent capivasertib dosing schedule of 400 mg twice daily, in combination with fulvestrant, in patients with aromatase inhibitor-resistant, HR-positive/HER2-negative advanced breast cancer without dose adjustment based on intrinsic factors, such as race, age, body weight, renal or hepatic function.

We assessed immune-mediated adverse events (imAEs) in the TOPAZ-1 (NCT03875235) study of durvalumab plus gemcitabine and cisplatin (GemCis) in advanced biliary tract cancer (aBTC).

This study assessed the safety, preliminary antitumor activity, and pharmacokinetics of HR070803 (a novel liposomal irinotecan) in combination with 5-FU/LV and oxaliplatin for treatment-naive patients with unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC).

Patients diagnosed with oral cavity cancers (OCCs) often delay seeking medical attention and so always pose a challenge for oncologists. Typically, surgery is the preferred initial treatment option. However, surgical resection may not be feasible in cases of advanced disease. Conversely, radiotherapy (RT) and chemotherapy (CT) have not been widely used as alternatives to surgery for curative treatment or as neoadjuvant therapy.

The clinical benefit of neoadjuvant immunochemotherapy in locally advanced cervical cancer (LACC) remains unclear. This single-arm, phase II study (Chinese Clinical Trial Registry, ChiCTR2200065392) aimed to evaluate the efficacy and safety of neoadjuvant anti-programmed cell death protein 1 (PD-1) antibody tislelizumab in combination with chemotherapy in treatment-naïve patients with stage IB3/IIA2 LACC. Enrolled patients received tislelizumab (200 mg, every 3 weeks) plus chemotherapy for 3 cycles before radical surgery. The primary endpoint was the pathological complete response (pCR). Secondary endpoints were objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1, disease-free survival, overall survival, and safety. Exploratory endpoints included tissue-based and blood-based biomarkers to identify the biological drivers behind the clinical outcomes. Between November 2022 and March 2024, 30 patients were enrolled. All patients completed 3 cycles of neoadjuvant immunochemotherapy and underwent radical surgery. The pCR was observed in 20 (66.7%) patients, and 4 (13.3%) patients achieved major pathological response (MPR), with an optimal pathological response rate (OPR) of 80.0%. The ORR was 90.0%, with 17 (56.7%) complete responses. Survival data were immature at the median follow-up of 14.7 months (data cutoff, December 31, 2024). Grade 3 treatment-related adverse events (TRAEs) and immune-related AEs occurred in 26.7% and 3.3% of patients, respectively. No treatment-related death occurred. Patients with pCR had significantly higher expression of PD-L1 CPS at baseline, and a strong relationship with immune-related signature (all p < 0.05). Neoadjuvant tislelizumab plus chemotherapy showed promising antitumor efficacy and a well-tolerated safety profile in patients with stage IB3/IIA2 LACC, and might be a potential option in this population.

Immune checkpoint inhibitors can be coadministered as a fixed-ratio combination (FRC) or administered as sequential infusions (ASI). Two randomized, open-label trials compared nivolumab + ipilimumab as a FRC versus ASI in patients with melanoma or renal cell carcinoma.

Pexidartinib is approved in the US, Taiwan, and Korea for adults with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery based on the phase III ENLIVEN study (NCT02371369). We report the final long-term efficacy and safety results from ENLIVEN.

Endocrine resistance is a major challenge in treating patients with ER+ /HER2- metastatic breast cancer (MBC) necessitating a switch from endocrine therapy to more toxic therapies. Mutations in ESR1 constitute a key mechanism of resistance to endocrine therapy in ER+ /HER2- BC. Therapies that overcome endocrine resistance are needed. Palazestrant is a novel oral complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD) belonging to a new class of ER-targeting agents that completely blocks estrogen-induced transcriptional activity, regardless of ESR1 mutation status. This first-in-human, open-label, multicenter, phase 1/2 dose-escalation/expansion study was designed to determine the recommended phase 2 dose (RP2D) and to evaluate safety, pharmacokinetics, and antitumor activity of palazestrant in patients with ER+ /HER2- MBC with disease progression on prior treatment.

The identification of homologous recombination deficient (HRD) tumor is now a crucial step for the therapeutic management of ovarian cancer. The HRD tumors are both sensitive to olaparib maintenance treatment and to platinum-based chemotherapy. Despite the large amount of HRD tests currently available, only a few HRD tests were prospectively validated on a clinical cohort of patients with ovarian cancer. To fulfil these challenges, our laboratory has recently developed a HRD test named GIScar (Genomic Instability Scar). Our HRD test was successfully validated on the retrospective cohort of PAOLA-1 clinical trial regarding the prediction of tumor sensitivity to olaparib. However, we have not yet validated GIScar on a prospective clinical cohort.