In-depth analysis of practice-changing oncology research, one article at a time.
Part 1 of a phase 1 trial of RO7589831 (VVD-133214), a covalent Werner syndrome helicase inhibitor, enrolled 88 patients with MSI and/or dMMR advanced solid tumors who had progressed on standard therapies. Among 66 MSI efficacy-evaluable patients, the disease control rate (DCR) was 74.2% (95% CI 63.9–82.9; 49/66) and the objective response rate (ORR) was 10.6% (7/66, confirmed RECIST v.1.1 partial responses).
uRARE-seq is a tumor-naive urine cell-free RNA (cfRNA) sequencing approach, applied to 683 urine samples from patients with cancer and controls. In the training cohort (100 controls, 151 bladder cancer samples), the detection model reached an AUC of 0.97, with a sensitivity of 95% at 90% specificity.
PIVOTAL is a randomized, open-label phase III trial of neoadjuvant intralesional daromun (L19IL2/L19TNF) followed by surgery versus up-front surgery in 256 adults with resectable locally advanced melanoma and at least one injectable skin or nodal lesion. This report is an updated analysis with a median follow-up of 36.8 months from random assignment (data cutoff November 28, 2025).
BL-B01D1-101 is an open-label, multicenter phase I study of izalontamab brengitecan (iza-bren; BL-B01D1), an EGFR-HER3 bispecific antibody-drug conjugate carrying a topoisomerase I inhibitor payload. The phase Ib extensive-stage small cell lung cancer (SCLC) cohort treated 52 patients who had progressed after platinum-based chemotherapy and a PD-(L)1 inhibitor.
VERSATILE-002 was a phase 2, open-label, multicenter, nonrandomized trial of the HPV16 E6/E7 peptide vaccine PDS0101 combined with pembrolizumab in HPV16-positive recurrent or metastatic head and neck squamous cell carcinoma. 87 patients were treated in two separately analyzed cohorts: immune checkpoint inhibitor (ICI)-naive and ICI-resistant.
A multicohort analysis of 589,766 adults aged 40 to 74 years without prior cancer, drawn from the Shanghai Men’s Health Study, the Shanghai Women’s Health Study and UK Biobank, estimated how much of the higher cancer incidence in males is attributable to 11 lifestyle factors and health conditions.
The phase 2 portion of ASPEN-06, a randomized, open-label trial, tested whether adding the CD47-blocking fusion protein evorpacept to trastuzumab, ramucirumab and paclitaxel (TRP) improves outcomes in previously treated, HER2-overexpressing advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
PATHFINDER 2, a prospective, interventional cohort study of 35,878 adults aged 50 and older with no clinical suspicion of cancer, evaluated the performance and safety of a blood-based multi-cancer early detection (MCED) test that analyzes cell-free DNA methylation patterns to detect a shared cancer signal and predict its tissue of origin.
A single-arm, phase 1b/2 trial (HERBOT) tested adding the HER2-targeted antibody trastuzumab to first-line nivolumab plus gemcitabine-cisplatin chemoimmunotherapy in 40 patients with HER2-positive, previously untreated, unresectable or metastatic biliary tract cancer — the first prospective study to introduce HER2-directed therapy immediately rather than reserving it for a later treatment line.
A prospective, 25-center registry analysis of 787 patients treated with laser interstitial thermal therapy (LITT) for primary or metastatic brain tumors — the largest such analysis to date — found that how completely a tumor is ablated, and how small it is to begin with, are the strongest drivers of survival after the procedure.
A prospective, non-randomized, two-cohort phase II trial (DISCOVARY) in 57 patients with androgen receptor (AR)-positive salivary gland carcinoma found that adding the LHRH agonist goserelin to the AR inhibitor darolutamide produced a substantially higher response rate than darolutamide alone, in a rare cancer with no approved systemic therapy.
Final, 15-to-17-year follow-up of the companion phase III SOFT and TEXT trials, conducted at 510 sites in 27 countries, reports that adding ovarian function suppression (OFS) to adjuvant endocrine therapy — and pairing OFS with the aromatase inhibitor exemestane rather than tamoxifen — reduced disease recurrence in premenopausal women with hormone receptor-positive early breast cancer, the longest follow-up yet published for this population.
A randomized phase II trial testing whether the CD27 costimulatory agonist varlilumab, combined with atezolizumab and the MEK inhibitor cobimetinib, could rescue checkpoint-inhibitor activity in previously treated, unresectable biliary tract cancer closed early for futility after a preplanned interim analysis.
A post-hoc analysis of the SYMPRO-Lung trial, a multicentre, stepped-wedge, cluster-randomised study across 14 Dutch centres, reports that weekly online patient-reported symptom monitoring was associated with longer overall survival in patients with lung cancer, extending follow-up well beyond the trial's original quality-of-life readout.
The phase 3 TAISHAN-302 trial's interim analysis reports that the B7-H3-targeted antibody-drug conjugate tambotatug pelitecan (Tam-Peli) significantly extends overall and progression-free survival compared with topotecan in patients with small-cell lung cancer (SCLC) that relapsed after platinum-based chemotherapy.
An exploratory analysis of the phase 3 KEYNOTE-826 trial reports that adding pembrolizumab to platinum-based chemotherapy (with or without bevacizumab) continues to show longer overall and progression-free survival than chemotherapy alone in persistent, recurrent, or metastatic cervical cancer, at a median follow-up of roughly five years (59.1 months).
The phase 3 COMBI-I trial's final long-term follow-up analysis reports a numerically longer overall survival with the anti-PD-1 antibody spartalizumab added to dabrafenib and trametinib, versus dabrafenib and trametinib alone, in 532 patients with BRAF V600-mutant advanced melanoma.
A randomized, double-blind, placebo-controlled phase 3 trial (NSABP B-59/GBG 96-GeparDouze) tested whether adding the PD-L1 inhibitor atezolizumab to neoadjuvant chemotherapy, followed by adjuvant atezolizumab, would improve outcomes over chemotherapy alone in 1,550 patients with stage II–III triple-negative breast cancer (TNBC).
A multicentre, externally controlled phase 2 trial (OPTIMUM/MUKnine) across 22 UK centres tested intensified induction with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone, followed by autologous stem-cell transplantation, extended consolidation, and daratumumab-lenalidomide maintenance in 107 patients with newly diagnosed high-risk multiple myeloma, compared against a molecularly matched external control cohort of 120 patients from the Myeloma XI trial.
An open-label phase 1b expansion cohort within a larger basket study tested Fc-enhanced anti-CTLA-4 antibody botensilimab plus anti-PD-1 antibody balstilimab in 123 patients with microsatellite-stable metastatic colorectal cancer without active liver metastases, most of whom were heavily pretreated.
A phase 3 registrational randomized trial (Neo-Healer, BCTOP study group) across 61 Chinese hospitals compared neoadjuvant anbenitamab plus HB1801 — with or without carboplatin — against standard trastuzumab, pertuzumab, and docetaxel (THP) in 521 patients with stage II or III ERBB2-positive breast cancer.
A phase 2, open-label, nonrandomized trial across five Chinese pediatric centers tested a bicistronic CD19/CD22 CAR T-cell product designed to reduce antigen-loss relapse after CD19-only CAR-T therapy in children and adolescents with relapsed or refractory B-cell acute lymphoblastic leukemia.
A first-in-human, open-label, single-arm phase I/II trial tested whether an intratumoral CD40 agonist (sotigalimab) added to systemic pembrolizumab could turn immunologically "cold" tumors "hot" in patients with immune-checkpoint-blockade-naive metastatic melanoma.
A global, randomized, double-blind, placebo-controlled phase 3 trial (SKYSCRAPER-01) tested whether adding the anti-TIGIT antibody tiragolumab to atezolizumab would improve outcomes over atezolizumab alone in previously untreated, PD-L1-high non-small cell lung cancer (NSCLC).
A single-center, non-randomized phase 2 basket trial tested ado-trastuzumab emtansine (T-DM1) across five disease-specific cohorts of HER2-amplified solid tumors, asking whether a shared molecular driver predicts benefit from a HER2-targeted antibody-drug conjugate regardless of tumor origin.
The phase 2 RADICAL trial (Alliance A031801) tested whether adding the bone-targeted radiopharmaceutical radium-223 to cabozantinib would reduce skeletal morbidity in metastatic renal cell carcinoma (mRCC) with bone metastases. The study closed early for futility after a prespecified interim analysis.
A prespecified biomarker analysis of the phase 3 RxPONDER (SWOG S1007) trial finds that serum anti-Müllerian hormone (AMH), a marker of ovarian reserve, identifies which women under 55 with hormone receptor-positive, HER2-negative, node-positive breast cancer actually benefit from adding chemotherapy to endocrine therapy — outperforming menopausal status and age as a predictor.
Updated results from the prospective, single-arm POSITIVE trial — now with a median follow-up of 71 months, up from 41 months at the original analysis — found no increase in breast cancer recurrence risk among young women with hormone receptor-positive disease who paused adjuvant endocrine therapy to attempt pregnancy.
In a prospective single-arm trial of 10,333 patients, an AI system called LiON (Liver DiagnOsis Network) met its primary endpoint for diagnosing liver malignancy on contrast-enhanced CT, achieving an AUC of 0.952 (95% CI: 0.942–0.961) — with an even higher AUC of 0.975 (95% CI: 0.971–0.979) in a separate 22,251-patient multicenter retrospective validation.
A nationwide Danish registry study of 8,134 patients found that age- and sex-standardized meningioma incidence nearly doubled between 2010 and 2023, rising from 6.4 to 12.6 cases per 100,000 person-years, while the proportion of diagnosed patients who ultimately received surgery fell from 43.9% to 23.4%.
A registry-based analysis of 11,681 US interventional cancer trials registered on ClinicalTrials.gov between 2008 and 2024 found that industry sponsors now outnumber federal sponsors nearly 5 to 1 (4.53-to-1 overall), with the ratio widening from 2.72-to-1 in 2008–2012 to 6.44-to-1 in 2019–2024.
The Step 2 randomization of NRG Oncology/RTOG 0848, a phase III trial of 354 patients with resected pancreatic head adenocarcinoma, found that adding chemoradiotherapy (CXRT) to adjuvant chemotherapy did not significantly improve overall survival across the full study population.
A retrospective cohort study of 16,924 men with prostate cancer, drawn from the Epic Cosmos national electronic health record dataset, found that new-onset metabolic syndrome developed in nearly 40% of patients within 12 months of starting concurrent androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI).
In a correlative biomarker analysis of the HCRN GU16-260 trial, non-exhausted CD8+ T cells were linked to higher response rates and longer progression-free survival in treatment-naive metastatic clear-cell RCC treated with first-line nivolumab.
Paired ctDNA profiling of 44 patients with RAS-mutant metastatic pancreatic cancer who progressed on daraxonrasib monotherapy found acquired RAS pathway alterations in 26 of 44 patients (59%), with mutant KRAS amplification the dominant mechanism (36%, 16 of 44).
In a prognostic analysis nested within the phase 2 c-TRAK TN trial, a tissue-free ctDNA assay detected molecular residual disease in 54 of 159 patients (34.0%) with early triple negative breast cancer, and detection was strongly associated with recurrence risk (HR, 27.2).
The Phase II FLARE-RT trial used mid-treatment FDG-PET response to selectively boost radiation dose (to 74 Gy, peak >90 Gy) only in the roughly one-third of unresectable NSCLC patients whose tumors were not responding, while treating responders with standard 60 Gy chemoradiation.
Long-term follow-up (median exceeding 10 years) of NRG Oncology RTOG 0539 validates a risk-adapted meningioma strategy: observation after gross total or subtotal resection for low-risk (WHO grade 1) disease, and radiotherapy for intermediate- and high-risk disease.
A first-cycle "adaptive therapy score," derived from a mathematical model of competing drug-sensitive and drug-resistant tumor cell populations, more strongly predicted time to progression than any standard PSA metric across two independent prostate cancer cohorts (n=53 total).
The FDA approved retifanlimab, a PD-1-targeting checkpoint inhibitor, in combination with carboplatin and paclitaxel for first-line treatment and as a single agent for second-line treatment of squamous cell carcinoma of the anal canal (SCAC) — the first checkpoint inhibitor approval in this disease.
The multicenter PRO B trial randomized 924 patients with metastatic breast cancer across 52 German centers to weekly alert-based electronic patient-reported outcome (ePRO) monitoring or usual quarterly PRO monitoring, with fatigue at 6 months as the primary endpoint.
A post-hoc analysis of the phase III PACIFIC trial (660 of 713 originally randomized patients; 449 durvalumab, 211 placebo) examined whether baseline exposure to proton pump inhibitors (PPIs) or antibiotics was associated with worse outcomes after consolidation durvalumab for unresectable stage III NSCLC, at a median follow-up of 62.4 months.
The phase III STELLAR trial (NCT02533271) randomly assigned 591 patients with distal or middle-third locally advanced rectal cancer to a short-course radiotherapy-based total neoadjuvant therapy regimen (SCRT-TNT) or standard long-course chemoradiotherapy (CRT); this update reports 5-year outcomes at a median follow-up of 68.7 months.
A single-center, investigator-initiated Phase II trial using a Simon two-stage design tested sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, in 50 evaluable patients with recurrent or persistent endometrial cancer who had progressed after platinum-based chemotherapy, enrolled between March 2020 and December 2024.
A single-center, investigator-initiated Phase Ib/II trial (NCI protocol 18-C-0110, NCT03554473) tested bintrafusp alfa — a bifunctional PD-L1/TGF-β fusion protein — alone or with chemotherapy in 37 patients with relapsed small cell lung cancer treated between 2019 and 2022.
A Phase 2 arm of the adaptive I-SPY2 platform trial (78 patients treated 2020-2021, compared against 350 historical controls) tested adding cemiplimab (anti-PD-1) and fianlimab (anti-LAG-3) to neoadjuvant chemotherapy in high-risk, stage II-III, ERBB2 (HER2)-negative breast cancer.
Phase 3 TORCH trial (241 patients, two tertiary centers in China, enrolled 2015-2024) randomized adults with unresectable, liver-confined, intermediate-stage (BCLC stage B) hepatocellular carcinoma 1:1 to transarterial chemoembolization (TACE) plus sequential radiofrequency ablation versus TACE alone.
A systematic review and trial-level meta-analysis of 21 randomized trials (9,165 pooled patients) in HR+/HER2-negative metastatic breast cancer compares investigator (local site)-assessed progression-free survival against blinded independent central review (BICR), asking whether the added cost and complexity of BICR is actually needed.
Randomized phase 3 comparison, from the maintenance ("R2") randomization of the ECOG-ACRIN ENDURANCE (E1A11) trial, of indefinite-duration versus fixed 2-year lenalidomide maintenance in 516 standard-risk multiple myeloma patients who did not undergo up-front autologous stem-cell transplantation.
A pooled, secondary mixture-cure-model analysis of three mature Phase III trials (HIMALAYA, CheckMate 9DW, RATIONALE-301) plus a large real-world cohort estimates how many patients with advanced hepatocellular carcinoma (HCC) achieve durable, cure-like outcomes on first-line immune checkpoint inhibitor (ICI) regimens.
Single-center, nonrandomized Phase 1 dose-exploration trial of META 10-19 — a CD19 CAR T-cell product engineered to also express interleukin-10 — delivered at ultralow cell doses to 13 heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Phase 1, first-in-human dose-escalation trial of DYP688 — an antibody-drug conjugate that targets the melanocyte antigen PMEL and delivers a Gq/11 signaling inhibitor payload — in 66 patients with metastatic uveal melanoma and other GNAQ/GNA11-mutant melanomas, a population largely excluded from the only approved therapy for this disease.
Retrospective, single-center biomarker cohort study of 39 patients with dMMR metastatic colorectal cancer treated with anti-PD-1 monotherapy at Mayo Clinic, using integrated exome, transcriptome, and immune-repertoire profiling to test whether quantitative MSI burden — not just binary MSI-high status — predicts benefit from checkpoint blockade
Randomized (2:1), open-label, international phase II trial of ceralasertib (an oral ATR inhibitor) plus durvalumab versus ceralasertib monotherapy in 151 patients with advanced melanoma that had progressed on prior anti-PD-(L)1 therapy
Open-label, single-center phase I dose-escalation and dose-expansion trial of IM96, an autologous GUCY2C-targeted CAR T-cell product, in 20 treated patients with microsatellite-stable, third- or later-line metastatic colorectal cancer — a population with very few remaining options
Open-label, multicenter phase 1 trial (Adult Brain Tumor Consortium, ABTC 1501) of the anti-LAG-3 antibody relatlimab, alone or combined with the anti-PD-1 antibody nivolumab, in 46 patients with first-time recurrent glioblastoma (GBM)
Open-label, single-arm phase 1b/2 trial of HRS-4642 — an intravenous, liposomal-nanoparticle KRAS-G12D inhibitor — added to gemcitabine and nab-paclitaxel (the "AG" backbone) in advanced KRAS-G12D-mutant pancreatic ductal adenocarcinoma (PDAC); 68 patients screened, 31 treated, 30 treatment-naive
Final post hoc analysis of the global, double-blind, placebo-controlled phase 3 TOPAZ-1 trial (685 patients randomized 1:1) reporting the longest published follow-up — approximately 4 years — of an immunotherapy-plus-chemotherapy regimen in first-line advanced biliary tract cancer (aBTC)
Multicenter, open-label, randomized phase 2 trial (TREASURE, AIO-TRK-0320) at 20 sites in Germany and Austria testing whether adding consolidative thoracic radiotherapy (TRT, 30 Gy in 10 fractions) to atezolizumab maintenance improves overall survival in extensive-stage small cell lung cancer (ES-SCLC) after induction chemoimmunotherapy; 96 patients screened, 68 randomized 1:1
Pooled analysis of the phase III CARES program (CAEL101-301 and CAEL101-302, n=406) testing whether adding the antifibril monoclonal antibody anselamimab to standard anti-plasma cell dyscrasia therapy improves a composite mortality/hospitalization endpoint in advanced (Mayo stage IIIa/IIIb) AL amyloidosis
Retrospective subset analysis of the CIRCULATE-Japan GALAXY registry (298 patients with resected colorectal liver metastases) testing whether ctDNA-defined molecular residual disease (MRD) status can identify who actually benefits from adjuvant chemotherapy (ACT) after liver resection
Randomised, double-blind, phase 3 study of 1,402 patients with surgically resected stage IIB–IV cutaneous melanoma across 205 global sites
VIKTORIA-1 is a Phase 3, open-label, randomized, global trial enrolling 392 PIK3CA wild-type patients with HR+/HER2- metastatic or locally advanced breast cancer who had progressed on prior CDK4/6 inhibitor plus nonsteroidal aromatase inhibitor therapy
Phase 3 randomized trial of 909 patients with previously untreated CLL across 174 sites in 13 countries
The Phase III OptiTROP-Lung04 trial randomized 376 patients with EGFR-mutated advanced NSCLC that progressed after EGFR-TKI therapy to sacituzumab tirumotecan (sac-TMT) monotherapy or platinum-based chemotherapy