Tumor biology and anticancer therapy: from mechanism papers to pivotal readouts and launches.
AstraZeneca announced that two phase 3 NSCLC trials met their primary endpoints: Enhertu, and Orpathys combined with Tagrisso. The same day, its PD-1/CTLA-4 bispecific antibody volrustomig failed in a phase 3 trial.
Why it matters: Two phase 3 NSCLC positive readouts and one PD-1/CTLA-4 bispecific failure released the same day allow comparison of same-target candidates in low PD-L1 expression populations.
AstraZeneca has stopped a phase 3 trial of volrustomig plus chemotherapy versus Keytruda plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer, on the recommendation of the Independent Data Monitoring Committee following its interim analysis.
Why it matters: IDMC ended the PD-L1-negative NSCLC phase 3 for futility, showing the limits of a bispecific replacing PD-1 monotherapy.
Using integrated spatial multi-omics, the study identified stem-like lymphoid niches (SLNs) organized by CD70+ ILC2s and Tpex cells, which predict hepatocellular carcinoma (HCC) response to PD-1/PD-L1 immunotherapy. Bacillus cereus-PI-PLC increased SLN abundance and synergized with PD-L1 blockade, revealing the potential of microbiota to therapeutically enhance cancer immunotherapy through SLNs in HCC.
Why it matters: Spatial multi-omics identified niches that predict immunotherapy response and revealed a synergistic mechanism of a specific microbiota component.
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.
Short-course radiotherapy total neoadjuvant therapy combined with immunotherapy achieved a pathologic complete response rate of 54.8% in locally advanced rectal cancer, from the Neo-STAR study by teams at the Fourth Hospital of Hebei Medical University, published in Cancer Communications (IF=28.4). The study enrolled 118 patients; the immunotherapy-combination group's pCR rate exceeded the control group by 17.3 percentage points, and the major pathologic response rate reached 61.9%.
Why it matters: Specific figures for pCR of 54.8%, MPR of 61.9%, and the 17.3-percentage-point gap versus control enable comparison across similar regimens.
Long-term follow-up results from the SEQUOIA trial have been published in the Journal of Clinical Oncology. First author Professor Mazyar Shadman of Fred Hutchinson Cancer Center led the analysis, which focuses on the long-term performance of zanubrutinib as first-line treatment of previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Why it matters: Long-term SEQUOIA follow-up data published in JCO provide extended-follow-up reference for zanubrutinib versus chemoimmunotherapy in untreated CLL/SLL.
A study published in Cell used CRISPR screening to search for new targets that could reverse age-related failure of antitumor immunity. The article reviews mechanisms by which T cell antitumor immunity declines with age, noting that older cancer patients have lower response rates to immune checkpoint inhibitors and are more prone to immune-related adverse events.
Why it matters: Age-related decline in T cell antitumor immunity underlies low ICB response rates in older patients, motivating the Cell study's CRISPR screen.
The FDA has approved BMS's Iberdomide (brand name Zenbexus), the first approved cereblon E3 ubiquitin ligase modulator (CELMoD) therapy. It is approved with subcutaneous daratumumab and hyaluronidase-fihj plus dexamethasone (ZDd) for adults with multiple myeloma who have received at least one prior line of therapy. Approval rests on the Phase 3 EXCALIBER-RRMM trial, which compared ZDd against daratumumab, bortezomib and dexamethasone (DVd) in relapsed or refractory multiple myeloma.
Why it matters: First FDA approval of a cereblon E3 ligase modulator, a new protein degrader class, for multiple myeloma.
Chemically induced skin tumors in mice arise predominantly from Lgr6+ and/or Lrig1+ stem cells of the upper hair follicle and only very rarely from Lgr5+ and Krt19+ bulge stem cells, based on fluorescent lineage tracing, single-cell transcriptomics, and duplex sequencing. Lgr6+ stem cells initiated by dimethylbenzanthracene expanded clonally after tumor promotion, carrying the canonical Hras Q61L mutation, while spontaneous Kras mutations expanded only when Hras was deleted, revealing competitive Hras-Kras interaction in clonal selection.
Why it matters: It pins the cell of origin for chemically induced skin tumors and uncovers Hras-Kras competition shaping clonal selection.
Lung transplant after contemporary staging and a dissemination-minimizing operative technique gave 1-year overall survival of 100.0% (0 deaths) in 17 patients with medically refractory, lung-limited, stage IV NSCLC, versus 40.8% (52 deaths) in 81 eligible patients treated with medical management alone, an absolute difference of 59.2 percentage points. One-year posttransplant survival in the NSCLC group matched organ stewardship expectations, 100% vs 88.1% among 306 recipients without cancer. The findings challenge the historical exclusion of these patients from transplant, though 2 recipients had died by extended follow-up.
Why it matters: It reports survival data on a transplant option historically withheld from stage IV NSCLC patients.
FANCA deficiency drives tumor progression and creates synthetic lethality with PARP inhibitors through a homologous recombination-independent mechanism. An in vivo CRISPR screen, validated across diverse human cancer models, shows FANCA loss disrupts FEN1 recruitment to replication forks, causing defective Okazaki fragment maturation, lagging-strand ssDNA gaps, and RPA exhaustion after PARPi treatment. FANCA-deficient, HR-proficient cells become PARPi-sensitive through lagging-strand transcription-replication conflicts reversible by RNA polymerase II inhibition or RNase H overexpression.
Why it matters: It defines FANCA loss as an HR-independent marker of PARP inhibitor sensitivity, potentially widening the eligible patient population.
The FDA granted accelerated approval on August 13, 2026 to iberdomide in combination with daratumumab-hyaluronidase fihj and dexamethasone (IberDd) for adults with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. Iberdomide is the first approved CELMoD drug for multiple myeloma, designed around the ubiquitin-proteasome system recognised by the 2004 Nobel Prize in Chemistry.
Why it matters: First CELMoD class drug approved for multiple myeloma, an approval relevant to clinicians treating relapsed patients.
The FDA has approved Bristol-Myers Squibb's iberdomide, a new CELMoD drug, for relapsed or refractory multiple myeloma. Approval is based on the EXCALIBER-RRMM trial, in which the iberdomide regimen doubled the rate of minimal residual disease-negative complete response versus daratumumab plus bortezomib and dexamethasone, 41% versus 21%. The company says it will continue exploring broader treatment options for multiple myeloma patients.
Why it matters: FDA approval of a first-in-class CELMoD drug for relapsed or refractory multiple myeloma, backed by MRD-negative complete response data.
The FDA has granted accelerated approval to Bristol Myers Squibb's iberdomide (brand name Zenbexus), the first CELMoD-class drug to receive FDA approval. It is approved in combination with daratumumab and dexamethasone for adults with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. Iberdomide works through targeted protein degradation, a mechanism distinct from traditional IMiDs such as lenalidomide and pomalidomide. Bristol Myers Squibb announced the approval on August 13, 2026.
Why it matters: First FDA approval of a CELMoD-class drug gives relapsed or refractory myeloma patients a new option.
The FDA has approved BMS's iberdomide for multiple myeloma, making it the first approved CELMoD drug, a new class of cereblon-directed protein degraders. The launch addresses declining sales of BMS's older immunomodulators, with Pomalyst revenue down 48% and Revlimid down 56% in the first half of this year.
Why it matters: FDA approval of the first-in-class CELMoD drug replaces two declining BMS multiple myeloma franchises.
On August 12, Nature published a study from a University of California, San Francisco team. Using what is described as the world's first in vivo genome-wide CRISPR screen in human T cells, the researchers identified P2RY8-GNAS as a new target that helps CAR-T cells infiltrate and fight solid tumors more effectively.
Why it matters: In vivo genome-wide CRISPR screening in human T cells identified P2RY8-GNAS, a candidate target and screening paradigm for solid tumor CAR-T amenable to comparison with existing approaches.
The FDA approved Bristol Myers Squibb's oral drug iberdomide, branded Zenbexus, for advanced multiple myeloma in patients who have received at least one prior line of therapy. It is the first drug in a new class of medicines for the blood cancer and the first cleared using a more sensitive measure of remission. Zenbexus will be used in combination with Darzalex and dexamethasone, and Bristol sees the class opening possibilities for more combinations.
Why it matters: First approval of a novel drug class for multiple myeloma, with a new remission standard used by FDA.
The FDA has granted accelerated approval to Bristol Myers Squibb's Zenbexus (iberdomide), the first cleared CELMoD therapy, in combination with Johnson & Johnson's Darzalex and dexamethasone for adults with previously treated multiple myeloma. The approval rests on the phase 3 Excaliber-RRMM trial, where the regimen achieved an MRD-negative complete response rate of 41% versus 21% for Darzalex, Velcade and dexamethasone at a median follow-up of 16 months. BMS must provide confirmatory PFS data expected this year, and its second CELMoD, mezigdomide, faces an FDA decision date of May 13, 2027.
Why it matters: First approval for a CELMoD drug and first new myeloma drug cleared directly on MRD as an endpoint.
The FDA has approved Bristol Myers Squibb's Iberdomide (Zenbexus) in combination with daratumumab and dexamethasone for patients with relapsed or refractory multiple myeloma. The approval, announced on August 13, makes Iberdomide the first cereblon E3 ubiquitin ligase modulator (CELMoD) therapy cleared by the FDA and the first product from BMS's CELMoD pipeline.
Why it matters: First FDA approval of a CELMoD therapy and of BMS's CELMoD pipeline in relapsed or refractory multiple myeloma.
On 12 August 2026, China's NMPA approved Akeso's supplemental new drug application for ivonescimab injection combined with chemotherapy as first-line treatment of advanced squamous non-small cell lung cancer. It is ivonescimab's third approved lung cancer indication. The regimen, supported by the Phase 3 HARMONi-6/AK112-306 study, is described as the first to show significant benefits in both progression-free survival and overall survival versus an anti-PD-1 antibody plus chemotherapy in a randomized, double-blind trial.
Why it matters: NMPA approval of a first-line squamous NSCLC indication backed by dual PFS and OS superiority over PD-1 plus chemotherapy.
