CD7 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory T-cell acute lymphoblastic leukemia (ALL). Supportive results of first-in-human studies of base-edited anti-CD7 CAR (BE-CAR7) T cells with triple C→T deamination-mediated knockouts of TCRαβ, CD52, and CD7 have been reported previously.

This phase II study (ALTER-H006; NCT05111366) evaluates adjuvant benmelstobart plus anlotinib in patients with high-risk recurrence (including ≥4 tumors, portal vein tumor thrombus [Vp1/2], or hepatic vein tumor thrombus [Vv1/2]) after hepatocellular carcinoma (HCC) resection. Primary endpoint is 1-year recurrence-free survival (RFS) rate. Secondary endpoints include overall survival (OS), 1-year OS rate, RFS, and safety. Median follow-up is 12.6 months. Among 37 patients enrolled, 1-year RFS rate is 59.7%, and median RFS is 15.6 months. Subgroups with Vp1/2 and Vv1/2 show median RFS of 18.2 months and not reached (NR), respectively. The longest recurrence-free duration is 25.9 months. Median OS is NR (1-year OS rate, 91.7%). Grade ≥3 treatment-related adverse events occur in 45.9% of patients, most commonly hypertension. No treatment-related deaths occur. Here, we show that adjuvant benmelstobart plus anlotinib is a feasible treatment option for HCC patients with high-risk recurrence after HCC resection, warranting confirmation in large-scale randomized clinical trials.

Immunostimulatory effects of PARP inhibitors could increase sensitivity to immune checkpoint inhibitors. The previous Phase II trial (MEDIOLA) reported clinical benefits of durvalumab and olaparib (D + O) in patients with germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer. Yet, the clinical activity of D + O in germline BRCA wild-type (gBRCAwt) triple-negative breast cancer (TNBC) remains unknown.

Measurable residual disease (MRD) can predict relapse in patients with advanced myelodysplastic neoplasms (MDS) or acute myeloid leukemia (AML). We report the long-term efficacy and safety of MRD-guided preemptive azacitidine treatment to prevent relapse in the phase 2 Relapse Prevention With Azacitidine (RELAZA2) trial. Patients with MDS or AML after either intensive chemotherapy only or consecutive allogeneic stem cell transplantation were prospectively screened for imminent relapse by molecular MRD assessment. Patients who became MRD positive (MRDpos) during screening received azacitidine for up to 2 years to prevent relapse. The primary end point was the proportion of patients alive and relapse-free 6 months after azacitidine start. Of 357 patients screened, 119 (33.3%) became MRDpos, of whom 95 (79.8%) were eligible for azacitidine treatment. The primary end point was met; 60 (63%) patients were relapse free (95% confidence interval, 54-71; P< .0001) 6 months after azacitidine initiation with no new safety signals. Of 60 patients achieving MRD response during the first 6 cycles of azacitidine, 31 (52%) maintained response without hematological relapse for ≥2 years after azacitidine initiation. The median treatment-free duration after azacitidine discontinuation was 20.8 months; the longest ongoing response was 104 months. After a median follow-up of 6.6 years, 15 initial responders (25%) remained alive and in remission. Among screened patients who remained continuously MRD negative, 60-month overall survival and relapse-free survival were 88% and 79%, respectively. Patients with continuously negative MRD display a very favorable prognosis. Most patients with MRD positivity can be effectively treated with azacitidine with potential long-term remission even after termination of azacitidine. This trial was registered at www.clinicaltrials.gov as #NCT01462578.

This multicenter, single-arm, Phase II study aimed to evaluate the efficacy and safety of fluorouracil, levofolinate, and irinotecan (150 mg/m2, standard dose in Japan) (FOLFIRI) plus ramucirumab (RAM) as second-line treatment for metastatic colorectal cancer (mCRC) in Japanese patients.

In the phase I/II Study 22 (NCT02519348) trial, objective response rates were 24.0% with STRIDE (single tremelimumab regular-interval durvalumab), 21.3% with durvalumab plus bevacizumab (D + B), and 11.5% with durvalumab monotherapy in unresectable hepatocellular carcinoma (uHCC). Increased proliferating CD8+ T cells were associated with improved efficacy of STRIDE versus durvalumab monotherapy. Here, analyses of changes in T-cell clonal expansion and gene expression signatures (GES) in peripheral blood were performed to explore the mechanisms of action associated with the anticancer activity of STRIDE and D + B versus durvalumab monotherapy.

Consolidation durvalumab following no progression on concurrent chemoradiotherapy (cCRT) is standard of care for unresectable stage III non-small-cell lung cancer (NSCLC). However, in clinical practice many patients receive sequential CRT (sCRT). The PACIFIC-5 trial aimed to evaluate the efficacy and safety of consolidation durvalumab for unresectable stage III NSCLC following no progression on cCRT or sCRT.

SWOG S2210 is a phase 2 trial testing the use of biomarker-guided neoadjuvant carboplatin, a safe and accessible chemotherapy agent, for patients with localized high-risk prostate cancer and inherited BRCA1/2 mutations. The endpoints are pathologic complete response rates and survival outcomes.

Advanced/metastatic soft tissue sarcomas (STSs) remain an unmet clinical need. We previously reported the feasibility and preliminary activity of trabectedin-olaparib combination in patients with advanced STS progressing after anthracycline-based regimens.

Whether the addition of bevacizumab to a programmed cell death protein-1 (PD-1) inhibitor plus chemotherapy can provide further survival benefits as first-line treatment in non-squamous non-small-cell lung cancer (NSCLC) without EGFR sensitising mutations, or ALK/ROS1 rearrangements, is unknown. We evaluated serplulimab (an anti-PD-1 antibody) plus HLX04 (a bevacizumab biosimilar) and chemotherapy in non-squamous NSCLC.

Pirtobrutinib, a highly selective, noncovalent Bruton tyrosine kinase inhibitor (BTKi), has shown efficacy and safety in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who received prior covalent BTKi. We report results, to our knowledge, from the first randomized head-to-head comparison of pirtobrutinib versus ibrutinib in BTKi-naïve CLL/SLL in both treatment-naïve (TN) patients and patients with relapsed/refractory (R/R) disease.

Stereotactic ablative radiotherapy (SABR) is increasingly used in the management of oligometastatic disease. However, variability in SABR plans raises questions about their impact on local control at SABR-treated lesions (LC). We aimed to explore whether quantitative dosimetric parameters could predict LC in head and neck squamous cell carcinoma (HNSCC) patients in the OMET (GORTEC 2014-04) trial.

Poly (ADP-ribose) polymerase (PARP) inhibitor use in endometrial cancer (EC) requires predictive biomarkers, currently lacking in clinical practice. This study assessed the incidence of homologous recombination deficiency (HRD) using genomic loss of heterozygosity (gLOH) and a machine learning-based HRD scar signature (HRDsig).

This study aimed to evaluate the antitumor effect and safety of neoadjuvant chemotherapy plus tislelizumab (a programmed death-1 inhibitor) for the treatment of resectable locally advanced oral or oropharyngeal squamous cell carcinoma (LAOOPSCC).

Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is characterized by poor response to traditional chemotherapy but heightened sensitivity to immune checkpoint inhibitors (ICIs). However, it is unclear whether envafolimab, a subcutaneous programmed death-ligand 1 inhibitor, provides comparable efficacy and safety as a neoadjuvant treatment in these patients compared to programmed cell death-1 inhibitors.

Pevonedistat, a potent NEDD8-activating enzyme inhibitor, has shown preclinical promise in overcoming platinum resistance and enhancing antitumor activity. This phase I study investigated the recommended dose (RD) and tolerability of pevonedistat in combination with capecitabine plus oxaliplatin (CapeOX) as third-line or later treatment in patients with unresectable advanced or recurrent gastric cancer (AGC). The study included a dose-finding cohort for determining the RD and an expansion cohort for assessing the efficacy and safety at the RD. Twelve patients were enrolled between April 2019 and September 2021. Dose-limiting toxicities (DLTs), including grade 2/3 aspartate transaminase/alanine transaminase (AST/ALT) elevation and treatment delays, occurred in the initial 2 patients at level 1 (20 mg/m2). After protocol amendment, no DLTs were observed at level 0 (15 mg/m2), which was determined as the RD. Common adverse events were decreased platelet count (67%), nausea (58%), and AST/ALT elevation (58%). A partial response was achieved in 2 patients (17%) and disease control was achieved in 8 (67%). Median overall survival was 9.3 months and progression-free survival was 4.4 months. Pevonedistat plus CapeOX was well tolerated and showed promising efficacy as salvage-line chemotherapy for AGC.

Cholangiocarcinoma is a rare, aggressive cancer often driven by FGFR2 fusions, which are targetable with inhibitors such as pemigatinib and futibatinib. However, resistance frequently develops due to acquired FGFR2 mutations. In this study, we aimed to evaluate the efficacy and safety of tinengotinib in previously treated patients with advanced cholangiocarcinoma.

We report the results of LINUX (NCT05594095), a multicenter, randomized, controlled phase II platform trial aiming to identify effective precision treatments for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer after resistance to cyclin-dependent kinase 4/6 inhibitor. A total of 105 patients were categorized into four similarity network fusion (SNF) subtypes by artificial intelligence-assisted classification and randomly assigned to receive subtyping-based precision therapy (N = 70) or treatment of physician's choice (N = 35). Results demonstrate superior primary endpoint of objective response rates in the subtyping-based groups compared to controls: 10% versus 0% for SNF1, 65% versus 30% for SNF2, 40% versus 30% for SNF3, and 70% versus 20% for SNF4. Grade 3-4 treatment-related adverse events occurred in 37% of both groups. These findings highlight the clinical benefits of subtyping-based precision therapies, particularly for SNF2 and SNF4 subtypes, warranting further validation in phase III trials.

Alterations in fibroblast growth factor receptor 2 (FGFR2) represent potential therapeutic targets in intrahepatic cholangiocarcinoma (ICC), yet they occur in only about 10% of patients. In this study, patients with advanced ICC are tested for FGFR2 alterations via pre-enrollment biopsy; those with alterations are excluded. Eligible patients receive locoregional gemcitabine combined with camrelizumab and surufatinib until disease progression or intolerable adverse events (AEs). Between July 2022 and June 2024, 23 eligible patients are enrolled. Twelve patients achieve partial response, resulting in an objective response rate of 52.2%. The median progression-free survival is 11.3 months, and the median overall survival is 20.3 months. Eighteen patients experience at least one AE, including one grade 3 event. Exploratory analysis indicates that responders show significantly higher tumor PD-L1 expression than non-responders do, with median tumor proportion scores of 8% and 2%, respectively. The study is registered at ClinicalTrials.gov (NCT05236699).

The aim of this Phase 1 study was to evaluate safety and tolerability of the alpha emitting therapy 224Ra-labeled microparticles (Radspherin®) and to establish the recommended dose for further development.