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Oct 14Wed
  1. nature.com62

    Talazoparib plus enzalutamide in high-volume metastatic hormone-naive prostate cancer: a randomized phase 2 trial

    Adding the PARP inhibitor talazoparib to enzalutamide improved prostate-specific antigen response in patients with high-volume metastatic hormone-sensitive prostate cancer in the randomized phase 2 ZZ-FIRST trial. Spatial transcriptomic analysis of paired biopsies showed that androgen receptor inhibition suppresses homologous recombination repair-related programs, and this suppression correlated with proliferation arrest rather than functional HRR deficiency.

    Why it matters: Links AR inhibition to HRR program suppression, giving a mechanistic basis for combining PARP inhibition with androgen receptor inhibitors.

Oct 13Tue
  1. Nat Med65

    Intravenous hyaluronidase-expressing oncolytic adenovirus with chemotherapy in metastatic pancreatic cancer: a randomized phase 2b trial.

    Adding intravenous VCN-01, a hyaluronidase-expressing oncolytic adenovirus, to gemcitabine and nab-paclitaxel improved outcomes as first-line therapy in metastatic pancreatic ductal adenocarcinoma. In the full analysis set, median overall survival was 10.8 versus 8.6 months (HR 0.57) and progression-free survival was 7.0 versus 4.6 months (HR 0.55, P = 0.011); response duration was 11.2 versus 5.4 months. The phase 3 evaluation is warranted.

    Why it matters: First randomized evidence that an intravenous oncolytic virus plus chemotherapy extends survival in metastatic pancreatic cancer.

  2. medrxiv.org41

    FORESEE: A prospective feasibility trial of functional precision oncology for metastatic breast cancer patients

    Organoid-based drug testing plus genomic characterization was feasible but limited by PDO establishment in HER2-negative metastatic breast cancer. Of 15 patients enrolled, 10 biopsies had adequate tumor content and PDOs were established in 4, an overall success rate of 40%, missing the primary endpoint of at least 46%. Results returned within 12 weeks informed treatment selection in all evaluable cases, and physicians used the information in 100% of successful cases.

    Why it matters: Quantifies the real-world success rate of functional precision oncology in metastatic breast cancer, showing PDO establishment as the bottleneck.

Oct 1Thu
  1. N Engl J Med64

    Giredestrant plus Everolimus in Advanced Breast Cancer.

    An all-oral regimen of giredestrant plus everolimus significantly prolonged progression-free survival over standard endocrine therapy plus everolimus in ER-positive, HER2-negative advanced breast cancer after a CDK4/6 inhibitor. Among 207 patients with ESR1-mutated tumors, median progression-free survival was 10.0 versus 5.5 months (hazard ratio 0.38); in the overall population of 373 patients, it was 8.8 versus 5.5 months (hazard ratio 0.56). Adverse-event rates were similar between groups.

    Why it matters: Phase 3 data show an all-oral targeted combination doubles progression-free survival after CDK4/6 inhibition, especially in ESR1-mutated tumors.

  2. Nat Med60

    Werner helicase inhibitor for advanced microsatellite instability solid tumors: a phase 1 trial.

    RO7589831 (VVD-133214), a first-in-class covalent inhibitor of Werner syndrome helicase, showed manageable safety and early antitumor activity in 88 patients with MSI and/or mismatch repair-deficient advanced solid tumors in part 1 of a phase 1 trial. TEAEs were mostly grade 1-2, with no grade 5 events and discontinuation in 3.4% (3/88). In 66 MSI efficacy-evaluable patients, disease control rate was 74.2%, objective response rate 10.6% (7 partial responses), median PFS 6.7 months and median OS 17.6 months; 150 mg and 600 mg BID were selected as recommended phase 2 doses.

    Why it matters: First-in-human data on a WRN covalent inhibitor, a synthetic lethal target for MSI cancers.

Sep 30Wed
  1. nature.com70

    Intravenous hyaluronidase-expressing oncolytic adenovirus with chemotherapy in metastatic pancreatic cancer: a randomized phase 2b trial

    Intravenous zabilugene almadenorepvec (VCN-01), a hyaluronidase-expressing oncolytic adenovirus, plus gemcitabine and nab-paclitaxel prolonged overall survival over chemotherapy alone in the randomized phase 2b VIRAGE trial in treatment-naive metastatic pancreatic cancer. The finding supports adding an oncolytic virus to standard first-line chemotherapy in this setting.

    Why it matters: First randomized evidence that an intravenous oncolytic adenovirus improves survival in metastatic pancreatic cancer.

Sep 29Tue
  1. nature.com54

    A synthetic lethal drug for microsatellite instability cancers

    Inhibition of the Werner syndrome helicase (WRN) enzyme exploits a new synthetic lethal vulnerability in cancers with microsatellite instability, a phase 1 trial shows. The approach offers a new way to target these tumors beyond immune checkpoint inhibition. No efficacy numbers are reported in the material.

    Why it matters: First clinical evidence that WRN inhibition can target microsatellite instability cancers beyond checkpoint inhibitors.

  2. nature.com54

    Werner helicase inhibitor for advanced microsatellite instability solid tumors: a phase 1 trial

    RO7589831, a first-in-class inhibitor of the synthetic lethal target Werner syndrome helicase, showed some partial responses in the dose-escalation stage of a phase 1 trial in patients with microsatellite instability and/or DNA mismatch repair-deficient solid tumors. The maximum tolerated dose was not reached.

    Why it matters: First clinical data for a Werner helicase inhibitor, a new synthetic lethal strategy in MSI tumors.

Sep 25Fri
  1. medrxiv.org56

    Tumour extrinsic neutrophil regulation in mesothelioma correlates with responsiveness to AXL and PD1 inhibition in MIST3, a phase IIA clinical trial

    AXL and PD1 inhibition with bemcentinib plus pembrolizumab met its primary endpoint in the phase IIA MIST3 trial in ICB naïve-relapsed mesothelioma, with a 12-week disease control rate of 46.2% (90% CI 29.2-63.8%); grade 3 or greater adverse events occurred in 53.9% of patients. Multiomic analyses linked response to NF2 loss, immune response signalling, epithelial mesenchymal transition, and neutrophil-related transcriptional programmes including SPI1, ETS2 and FLI1 activation. Gut microbiota composition differed between responders and non-responders and correlated with neutrophil-associated transcription programmes, IRF3 and TLR2.

    Why it matters: Phase IIA evidence that neutrophil and gut microbiota features track response to AXL-PD1 inhibition in mesothelioma.

Sep 24Thu
  1. Nature Medicine56

    Evorpacept plus trastuzumab, ramucirumab and paclitaxel in HER2-positive gastric cancer: a randomized phase 2 trial

    Adding the CD47 inhibitor evorpacept to trastuzumab, ramucirumab and paclitaxel (TRP) produced a higher objective response rate than TRP alone in patients with HER2-positive advanced gastric cancer that had progressed on anti-HER2 treatment. The finding comes from the phase 2 part of the randomized ASPEN-06 trial. Response was associated with CD47 and HER2 expression.

    Why it matters: It tests CD47 blockade as a way to overcome resistance to anti-HER2 therapy in gastric cancer.

Sep 22Tue
  1. Nature Medicine50

    Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study

    The PATHFINDER 2 study evaluated the safety and performance of a blood-based multi-cancer early detection test in an intended-use population of more than 35,000 participants aged 50 years or older. It reports outcomes on how the test performs when used prospectively in people without a prior cancer diagnosis. The findings add interventional evidence on safety and performance in the intended-use setting.

    Why it matters: Large interventional evidence on a multi-cancer early detection blood test in its intended-use population.

  2. Nature Medicine52

    Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial

    Secondary endpoint analyses from the NHS-Galleri randomized controlled trial characterize how a blood-based multi-cancer early detection test performed when added to usual care in more than 142,000 participants without suspicion of cancer. The trial evaluated the test's performance as a screening tool in a general population, offering data on its behavior outside diagnostic settings.

    Why it matters: Reports performance data for a multi-cancer early detection blood test in a randomized trial of over 142,000 people.

  3. Nature Medicine52

    Trastuzumab plus nivolumab with gemcitabine and cisplatin as first-line therapy for HER2-positive unresectable biliary tract cancer: a phase 1b/2 trial

    A phase 1b/2 trial tested trastuzumab combined with nivolumab, gemcitabine and cisplatin as first-line therapy for HER2-positive unresectable biliary tract cancer. The regimen showed encouraging clinical response rates, and HER2 expression was associated with clinical benefit. The results support HER2 status as a marker guiding trastuzumab-based treatment in this population.

    Why it matters: First data on adding trastuzumab and nivolumab to standard gemcitabine-cisplatin in HER2-positive biliary tract cancer.

Sep 15Tue
  1. Sci Adv55

    Synthetic long peptide and DNA personalized cancer vaccines induce robust neoantigen-specific T cell responses in pancreatic cancer.

    Personalized cancer vaccines, delivered as synthetic long peptide or DNA formulations after resection and adjuvant chemotherapy, were safe and immunogenic in pancreatic ductal adenocarcinoma: two phase 1 trials showed no grade ≥3 adverse events and induced polyclonal neoantigen-specific T cell responses confirmed by IFN-γ ELISpot, intracellular cytokine staining, and T cell receptor clonotype reconstruction. Compared with a propensity-matched cohort, vaccine recipients showed a trend toward longer median overall survival (4.4 versus 3.5 years, log-rank P = 0.23). The results establish feasibility of neoantigen vaccination in a tumor considered unresponsive to standard immunotherapy.

    Why it matters: It shows personalized neoantigen vaccines are safe and immunogenic in PDAC, a cancer unresponsive to standard immunotherapy.

  2. nature.com50

    Oral KRAS G12D inhibitor GFH375 for previously treated advanced solid tumors with KRASG12D mutations: a phase 1 trial

    The oral dual on-off binding KRAS G12D inhibitor GFH375 was evaluated in a phase 1 trial in patients with previously treated KRASG12D-mutated advanced solid tumors. Most treatment-related adverse events were low-grade, but there was one treatment-related death. Response rates were described as encouraging in non-small cell lung cancer and pancreatic cancer.

    Why it matters: First-in-human phase 1 data on an oral KRAS G12D inhibitor across KRASG12D-mutated solid tumors.

Sep 11Fri
  1. nature.com51

    Teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: a randomized phase 2 trial

    Teclistamab produced higher rates of complete clinical responses than lenalidomide-dexamethasone in patients with high-risk smoldering multiple myeloma in the randomized phase 2 ImmunoPRISM trial. Longer follow-up is needed to determine whether it durably prevents progression to multiple myeloma.

    Why it matters: First randomized comparison of teclistamab against lenalidomide-dexamethasone in high-risk smoldering myeloma.

Sep 10Thu
  1. Nat Med56

    Atezolizumab in early triple-negative breast cancer: the randomized phase 3 NSABP B-59/GeparDouze trial.

    Adding atezolizumab to neoadjuvant taxane-carboplatin-anthracycline chemotherapy did not significantly improve event-free survival in stage II-III triple-negative breast cancer, with an HR of 0.80 (95% CI, 0.62-1.03; P = 0.083) and a 4-year EFS difference of 3.3%. Prespecified subgroup analysis suggested benefit in patients with clinical lymph node involvement (P interaction = 0.039), and an exploratory mRNA subset analysis pointed to basal-like immune-activated tumors as potential responders. Immune-related adverse events occurred in 27.6% with atezolizumab versus 11.4% with placebo.

    Why it matters: Negative phase 3 result for checkpoint inhibition in early TNBC, with subgroup data pointing to who might still benefit.

Sep 5Sat
  1. Lancet72

    Liver resection after atezolizumab and bevacizumab versus maintenance therapy for locally advanced hepatocellular carcinoma (TALENTOP): a multicentre, open-label, randomised, phase 3 trial.

    Liver resection after response to atezolizumab plus bevacizumab prolonged time to treatment failure in advanced hepatocellular carcinoma with macrovascular invasion and no extrahepatic metastasis. In the phase 3 TALENTOP trial, 201 responders were randomised to surgery plus 12 months of the combination or maintenance therapy; median time to treatment failure was 20·4 versus 11·8 months (hazard ratio 0·60, p=0·015). Grade 3 or 4 treatment-related adverse events were more frequent with surgery (39% vs 21%).

    Why it matters: Randomised phase 3 evidence that resection adds benefit after systemic therapy in advanced hepatocellular carcinoma.

Sep 4Fri
  1. Lancet74

    [177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial.

    Adding 177Lu-PSMA-617 to androgen deprivation therapy plus an androgen receptor pathway inhibitor reduced the relative risk of radiographic progression or death by 28% in PSMA-positive metastatic APMN/S prostate cancer, meeting the primary endpoint of prolonged radiographic progression-free survival. In the phase 3 PSMAddition trial, 572 patients per arm were randomised; radiographic progression or death occurred in 24% of the 177Lu-PSMA-617 arm versus 30% of the control arm. Grade 3 or worse adverse events occurred in 51% versus 43%, with dry mouth the most common event in the 177Lu-PSMA-617 arm.

    Why it matters: It tests PSMA-directed radioligand therapy in first-line metastatic hormone-sensitive disease, earlier than current approved use.

Sep 3Thu
  1. JAMA67

    YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism in Patients With Cancer: A Randomized Clinical Trial.

    The YEARS algorithm was as safe as direct computed tomographic pulmonary angiography (CTPA) for ruling out acute pulmonary embolism in patients with active cancer. In the per-protocol analysis, 5 of 282 patients (1.8%) managed by YEARS vs 15 of 273 (5.5%) by CTPA only had symptomatic venous thromboembolism or possible PE-related death within 90 days (absolute risk difference, -3.7%; upper bound of 99.9% CI, 1.4%), and 22% of YEARS patients avoided CTPA entirely. This challenges guideline advice to send all cancer patients with suspected PE straight to CTPA.

    Why it matters: Randomized evidence that YEARS can rule out pulmonary embolism in cancer patients as safely as CTPA while sparing 22% the scan.

  2. N Engl J Med64

    Daraxonrasib for Previously Treated RAS-Mutant Non-Small-Cell Lung Cancer.

    Daraxonrasib (RMC-6236), an oral RAS(ON) multiselective inhibitor, showed antitumor activity in 136 previously treated patients with advanced RAS-mutant NSCLC: objective response occurred in 31% at doses of 120 mg or less, 34% at 160 to 220 mg, and 37% at 300 mg once daily. Adverse events of grade 3 or higher occurred in 54%, including four grade 5 events, with rash, diarrhea, nausea, vomiting, and mucositis or stomatitis each affecting at least 30% of patients.

    Why it matters: First safety and efficacy data for a pan-RAS inhibitor across multiple doses in previously treated RAS-mutant NSCLC.

Sep 2Wed
  1. JAMA43

    Addition of High-Dose Vitamin D3 to Standard Treatment in Patients With Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703).

    High-dose vitamin D3 did not improve outcomes over standard-dose vitamin D3 when added to mFOLFOX6 or FOLFIRI plus bevacizumab in previously untreated metastatic colorectal cancer. In the phase 3 SOLARIS trial of 455 patients, median PFS was 11.8 months vs 10.3 months (P = .25), with no differences in response rate or overall survival. The finding contradicts the earlier phase 2 signal and closes the question for front-line use.

Sep 1Tue
  1. nature.com68

    Atezolizumab in early triple-negative breast cancer: the randomized phase 3 NSABP B-59/GeparDouze trial

    Adding atezolizumab to neoadjuvant chemotherapy did not improve event-free survival in the phase 3 NSABP B-59/GeparDouze trial of patients with early-stage triple-negative breast cancer, missing its primary endpoint. Translational analyses identified tumor microenvironment-dependent determinants of response, indicating basal-like immune-activated tumors may respond to atezolizumab plus chemotherapy.

    Why it matters: Negative phase 3 result for atezolizumab in early triple-negative breast cancer, with biomarker data indicating which tumors may still benefit.

Aug 31Mon
  1. Lancet68

    Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial.

    Belzutifan plus lenvatinib extended progression-free survival over cabozantinib in previously treated advanced clear-cell renal cell carcinoma. In the phase 3 LITESPARK-011 trial, 747 patients with disease progression after anti-PD-1 or anti-PD-L1 therapy were randomly assigned to belzutifan-lenvatinib or cabozantinib. Progression-free survival by masked independent central review was significantly longer with belzutifan-lenvatinib, while overall survival did not differ significantly, and the authors suggest belzutifan-lenvatinib may become a new standard of care in this setting.

    Why it matters: Phase 3 data on a potential new standard of care after checkpoint inhibitor therapy in advanced clear-cell renal cell carcinoma.

Aug 29Sat
  1. N Engl J Med71

    First-Line Sunvozertinib in NSCLC with EGFR Exon 20 Insertion Mutations.

    First-line sunvozertinib extended median progression-free survival to 10.3 months versus 7.5 months with carboplatin-pemetrexed in advanced nonsquamous NSCLC with EGFR exon 20 insertion mutations (hazard ratio 0.65; P<0.001), in a phase 3 trial of 324 patients. Objective response was 58.9% versus 31.1%, with median duration of response of 11.2 versus 7.1 months. The findings support moving sunvozertinib, already accelerated-approved in later lines, into first-line use.

    Why it matters: Phase 3 evidence that sunvozertinib can replace platinum-pemetrexed as first-line therapy for EGFR exon 20 insertion NSCLC.

Aug 25Tue
  1. JAMA75

    Adjuvant Nivolumab vs Observation in Resected Non-Small Cell Lung Cancer: A Randomized Clinical Trial.

    Adjuvant nivolumab after upfront surgery did not improve disease-free survival in resected non-small cell lung cancer. Median disease-free survival was 71.3 months with nivolumab vs 68.8 months with observation (hazard ratio, 0.97; 1-sided P = .39), and the trial was stopped for futility. This contrasts with the established benefit of preoperative and perioperative nivolumab in this setting.

    Why it matters: A negative phase 3 trial clarifies that adjuvant nivolumab adds no benefit after upfront surgery in resected NSCLC.

Aug 23Sun
  1. N Engl J Med88

    Selpercatinib in Early-Stage RET Fusion-Positive Non-Small-Cell Lung Cancer.

    Adjuvant selpercatinib for up to 3 years after definitive therapy sharply reduced recurrence in RET fusion-positive NSCLC. In the 109 patients with stage II or IIIA disease, 2-year investigator-assessed event-free survival was 92% with selpercatinib versus 61% with placebo (hazard ratio 0.17; P<0.001), and blinded independent central review was consistent. The findings extend selpercatinib from advanced disease into the early-stage, curative-intent setting.

    Why it matters: First phase 3 evidence that a RET inhibitor works as adjuvant therapy in early-stage NSCLC.

Aug 20Thu
  1. nature.com47

    Intercepting pancreatic cancer with a vaccine

    An off-the-shelf vaccine targeting mutant KRAS safely and durably activated T cell responses in healthy people at high risk of developing pancreatic cancer, according to a phase 1 study published in Nature Medicine. The result indicates that a ready-made vaccine can engage the immune system against a key driver mutation before cancer arises. It points toward preventive interception of pancreatic cancer in high-risk individuals.

Aug 19Wed
  1. N Engl J Med88

    Talquetamab-Daratumumab in Relapsed or Refractory Myeloma.

    In a phase 3 trial of relapsed or refractory multiple myeloma after at least one prior line of therapy, talquetamab plus daratumumab (Tal-D) or with pomalidomide (Tal-DP) beat daratumumab-pomalidomide-dexamethasone (DPd) on progression-free survival: 24-month estimates of 81.3% and 77.6% versus 51.2%, with hazard ratios of 0.28 and 0.33. Complete response or better reached 71.1% and 69.0% versus 34.5%, and MRD-negative complete response 52.3% and 46.3% versus 15.9%. The results position GPRC5D-directed bispecific therapy earlier in the treatment sequence.

    Why it matters: Phase 3 data show talquetamab regimens outperforming standard daratumumab-based therapy in relapsed myeloma after just one prior line.

Aug 18Tue
  1. Nat Med60

    First-line PD-1/VEGF bispecific antibody plus chemotherapy in triple-negative breast cancer: a phase 2 trial.

    Ivonescimab plus paclitaxel or nab-paclitaxel as first-line therapy produced an objective response rate of 80.0% (95% CI 63.1-91.6) in 35 evaluable patients with locally advanced unresectable or metastatic triple-negative breast cancer, including 2 complete and 26 partial responses. In the 36-patient single-arm phase 2 trial, all patients had treatment-related adverse events, 58.3% were grade 3 or higher, and no treatment-related deaths occurred. The PD-1/VEGF bispecific plus chemotherapy pairing offers a first-line option for this population that merits further investigation.

    Why it matters: It tests a PD-1/VEGF bispecific antibody as first-line therapy in triple-negative breast cancer, where systemic options are limited.

Aug 17Mon
  1. Cancer Cell67

    Perioperative tislelizumab plus chemotherapy for locally advanced gastric cancer: A randomized, prospective phase 2 trial.

    Adding perioperative tislelizumab to chemotherapy raised the major pathological response rate in tsMHC-II-positive operable locally advanced gastric or gastroesophageal junction cancer (61.8% vs. 26.5%, p = 0.003), meeting the primary endpoint of the phase 2 Mountain-02 trial in 136 patients. No significant benefit appeared in tsMHC-II-negative patients, and tsMHC-II positivity also tracked with higher pCR (32.4% vs. 5.9%). The results position tumor-specific MHC class II expression as a candidate biomarker for selecting patients for perioperative immunotherapy.

    Why it matters: Identifies a predictive biomarker that separates responders from non-responders to perioperative immunotherapy in gastric cancer.

CBACBA Frontier Insights (CFI)Chinese Biopharmaceutical Association (CBA)www.cba-usa.org