New in Oncology - Oct 10, 2025
Smarter targeting, longer control: seven data standouts + five trial spotlights (including a protein degrader)
THIS WEEK’S BREAKTHROUGHS:
Seven signals: response where it counts, gentler delivery where it matters.
Of this week’s 7 notable findings, we’re spotlighting 4 (and a head scratcher):
🏆 Low pCR, surprisingly strong long-term control. Eribulin→AC in HER2-negative IBC showed very low pCR but high 5-yr EFS—hinting at benefit beyond pCR in an HR+-heavy cohort; small sample cautions apply.
🏆 Responses concentrated where the biomarker is high. Tusamitamab ravtansine hit ~20% ORR in high-CEACAM5 nonsquamous disease with manageable ocular AEs—enrichment is the lever.
🏆 A real signal in a rare slice. Glecirasib posts ~47% ORR in G12C-mutant PDAC, topping prior agents in small cohorts; durability/resistance will set its ceiling.
🏆 Physical radiosensitization boosts TARE. Ultrasound-triggered microbubbles plus Y-90 lifts CR/PR and halves death hazard in Phase II—multicenter confirmation next.
🤔 HEAD SCRATCHER OF THE WEEK: TTFields after SRS delayed intracranial progression in NSCLC brain mets without WBRT-like neurotoxicity—an intriguing non-systemic add-on as programs weigh feasibility/adherence.
7 NEW FINDINGS
Breast Cancer (1) • NSCLC (3) • PDAC (1) • HCC (1) • Cholangiocarcinoma (1)
THIS WEEK’S NEW TRIALS:
Five spotlights: KRAS to KLK2, tiles in the OR, and two first-in-human shots.
Out of 13 new cancer trials this week, we have five to spotlight:
🏆 Divarasib + pembrolizumab vs pembro+chemo in 1L KRAS G12C NSCLC — KRASi+PD-1 combo aiming to replace chemo-IO. (NCT06793215)
🏆 GammaTile at surgery to jump-start RT in newly diagnosed GBM — randomized vs standard chemoradiation. (NCT07195591)
🏆 Pasritamig (KLK2×CD3) post-ARPI mCRPC — double-blind OS trial of step-up T-cell engager vs placebo+BSC. (NCT07164443)
🏆 Dual-target ADC AVZO-103 (Nectin-4/Trop-2) — first-in-human mono/combination study across epithelial tumors. (NCT07193511)
🏆 ST-01156 RBM39 degrader — first-in-human oral targeted protein degradation in advanced solid tumors. (NCT07197554)
13 NEW TRIALS
NSCLC (1) • Glioblastoma (CNS) (2) • Prostate Cancer (1) • Colorectal Cancer (1) • Bladder Cancer (1) • Sarcoma (1) • Multiple Myeloma (1) • Solid Tumors (5)
7 New Findings This Week
Breast Cancer
🏆 SPOTLIGHT: Fundamentally interesting. Smaller bang but with a larger buck...Eribulin+AC (microtubule inhibitor + anthracycline/alkylator) in HER2-negative IBC shows very low pCR but high 5-yr EFS
Eribulin (microtubule inhibitor with anti-angiogenic effects) sequenced with doxorubicin/cyclophosphamide (AC) was tested as neoadjuvant therapy in a Phase II study for newly diagnosed HER2-negative inflammatory breast cancer (IBC) (n=22; 86% HR+; NCT02623972). pCR was 1/22 (4.5%), yet all patients proceeded to curative-intent surgery and radiation, and with 76-mo median follow-up, 5-yr EFS was 85.6% (95% CI 61.4–95.1). Safety was as expected for cytotoxic chemotherapy: any grade≥3 AE in 31.8% (neutropenia 22.7%); early DCE-MRI showed decreased tumor vascularization after 1 week. While historical anthracycline/taxane neoadjuvant regimens in HER2-negative/HR+ or IBC settings report pCR around 12–33% and 5-yr outcomes often nearer 40–70%, this cohort’s pCR was below typical ranges but longer-term EFS looks higher—interpret cautiously given small, HR+-enriched sample.
Take Home: If validated in a larger, biomarker-stratified cohort, the disconnect between low pCR and favorable 5-yr EFS suggests eribulin→AC/AC→eribulin may benefit HR+ IBC via non-pCR pathways (e.g., vascular effects)—but small n, HR+ predominance, and wide CIs demand confirmation before any shift in neoadjuvant practice.
🔗 https://pubmed.ncbi.nlm.nih.gov/41024110
Non-Small Cell Lung Cancer (NSCLC)
🏆 SPOTLIGHT: Despite lackluster ORR, the long DOR and high-expression enrichment demonstrate real biology. We can’t wait to see the results with a topo1 payload (and perhaps also in CRC)...CEACAM5-ADC tusamitamab ravtansine posts 20% ORR in high-CEACAM5 NSq NSCLC
Tusamitamab ravtansine (SAR408701), an antibody-drug conjugate targeting CEACAM5 with a maytansinoid (DM4) payload, was evaluated in a Phase 1b dose-expansion (NCT02187848) of advanced/metastatic nonsquamous NSCLC selected by CEACAM5 IHC. At 100 mg/m² Q2W, high expressors (≥2+ in ≥50% cells; n=64) achieved ORR 20.3% (13 PRs), median DOR 6.7 mo, and median time-to-progression 3.7 mo (95% CI 2.7–5.1); moderate expressors (1–49% cells; n=28) had ORR 7.1% and TTP 2.8 mo. TEAEs led to dose modifications in 37% and discontinuation in 5.4%; corneal AEs occurred in 38% (mostly grade 1/2, reversible). Relative to second-line standards, activity in high expressors exceeds typical docetaxel ORR (~14%) and approaches ramucirumab+docetaxel PFS (4.5 mo) but with similar PFS to docetaxel (≈3.0 mo)—suggesting benefit is mainly response-driven; importantly, the high-CEACAM5 population is ~25% of NSq-NSCLC by IHC.
Take Home: Concentrated activity in the ~25% “high-CEACAM5” segment with manageable ocular toxicity makes this ADC a plausible alternative where response matters, but without a PFS/OS edge over ram+doc yet, differentiation may depend on biomarker enrichment, eye-tox management, or combination strategies.
🔗 https://pubmed.ncbi.nlm.nih.gov/41031047
Trastuzumab deruxtecan (HER2-targeted ADC) anchors 2L+ HER2-mutant NSCLC—~49% responses with ILD risk managed at 5.4 mg/kg
Trastuzumab deruxtecan (T-DXd), a HER2-targeted antibody-drug conjugate (topoisomerase-I payload), is reviewed as a second-line option for metastatic HER2-mutant NSCLC. Across pivotal studies, the 5.4 mg/kg dose yields confirmed ORR ~49% with durable responses (median DoR ~16.8 mo) and a lower ILD incidence than 6.4 mg/kg; ILD/pneumonitis remains the key toxicity (any-grade ~12%, fatal ~0.9%) requiring early detection and management. Versus common 2L benchmarks—docetaxel ORR ~10–14% (PFS ≈3 mo) and ramucirumab+docetaxel PFS ≈4.5 mo—T-DXd delivers substantially higher response rates, though cross-trial PFS/OS comparisons remain cautious.
Take Home: For the ~2–4% of NSCLC with HER2 mutations, T-DXd 5.4 mg/kg offers class-leading tumor shrinkage with a boxed-warning ILD profile—future differentiation will hinge on optimizing ILD mitigation and defining benefit vs ram+doc in randomized or real-world head-to-heads.
🔗 https://pubmed.ncbi.nlm.nih.gov/41032684
🤔 HEAD SCRATCHER OF THE WEEK: TTFields show benefit again!TTFields (200 kHz antimitotic fields) after SRS delays intracranial progression in NSCLC brain mets
Tumor Treating Fields (TTFields), delivered by scalp arrays, were started after stereotactic radiosurgery (SRS) in the Phase 3 METIS trial (NCT02831959) for 1–10 brain metastases from NSCLC (n=298). Versus SRS alone, TTFields significantly prolonged time to intracranial progression (HR 0.72, 95% CI 0.53–0.98; Fine–Gray P=0.044) with lower cumulative progression rates at 2, 6, 12, and 24 months (13.6% vs 22.1%; 33.7% vs 46.4%; 46.9% vs 59.4%; 53.6% vs 65.2%). In the immune-checkpoint inhibitor subgroup (n=118), effects were larger (TTIP HR 0.63; TTDP HR 0.41, post-hoc). Safety was mainly grade≤2 skin reactions, with preserved QoL and no cognitive decline signal. Benchmarks: with SRS alone, 12-mo intracranial control is typically ~50%—METIS control ~40.6% vs 53.1% with TTFields—while adding WBRT can raise intracranial control to ~85% but at a cognitive cost; METIS suggests TTFields improves control without WBRT-like neurotoxicity.
Take Home: For patients receiving SRS (especially alongside ICI), TTFields offers a non-systemic way to extend intracranial control without QoL trade-offs—OS benefit remains unproven, so adoption will hinge on real-world feasibility, adherence, and confirmation of the ICI interaction.
🔗 https://pubmed.ncbi.nlm.nih.gov/41033612
Pancreatic Ductal Adenocarcinoma (PDAC)
🏆 SPOTLIGHT: A small but important success. It paves the way forward to improving outcomes for PDAC (with hopes that G12D works as well).Glecirasib (KRAS G12C) posts 47% ORR in PDAC; pooled ORR 51% across non-NSCLC/CRC solid tumors
Glecirasib (JAB-21822) is an oral covalent KRAS G12C inhibitor. A pooled Phase I/II analysis (NCT05009329/NCT05002270) in rare G12C tumors outside NSCLC/CRC (n=54; PDAC n=32, BTC n=8, others) reported confirmed ORR 50.9% overall; PDAC ORR 46.9% with mPFS 5.5 mo and mOS 10.8 mo; BTC ORR 71.4%. Median PFS/OS overall were 6.9/10.8 mo. Safety was manageable: TRAEs in 94.4%, grade≥3 in 27.8%, with no fatal events or discontinuations due to TRAEs. Context: PDAC G12C is uncommon (~1–3% of PDAC), and late-line chemotherapy typically yields ORR 0–15% and short PFS—while prior KRAS G12C inhibitors in PDAC achieved ORR ~21% (sotorasib) and ~33% (adagrasib), making the PDAC ORR here comparatively high, though numbers are small and uncontrolled.
Take Home: If confirmed prospectively—with blinded central review and regimen-specific cohorts—the signal suggests a step up over historical PDAC benchmarks and prior G12C agents in this slice of patients; durability, resistance biology, and combination strategies (e.g., SHP2) will decide how quickly this moves from “intriguing” to “impactful.”
🔗 https://pubmed.ncbi.nlm.nih.gov/41037823
Hepatocellular Carcinoma (HCC)
🏆 SPOTLIGHT: WOW! Major improvements for HCC by introducing microbubbles in this phase II from Thomas Jefferson University.Ultrasound-triggered microbubble radiosensitization + Y-90 TARE lifts CR/PR and survival in HCC (Phase II RCT)
Ultrasound-triggered microbubble destruction (UTMD)—a physical radiosensitizer that perturbs tumor vasculature—was added to yttrium-90 transarterial radioembolization (TARE) in a randomized Phase II trial of hepatocellular carcinoma (n=98). Compared with TARE alone, UTMD+TARE improved objective response distribution by mRECIST (CR/PR 96% vs 66%, P=0.01) and reduced mortality risk (HR 0.51, 95% CI 0.28–0.95, P=0.03); vitals and routine labs showed no between-arm safety signal. As context, typical TARE series report CR ~19% and PR ~36% (~55% CR/PR) and median OS in the ~14–24 mo range—so the response lift here exceeds usual TARE benchmarks, with survival benefit suggested by the randomized HR.
Take Home: If reproduced multicenter with standardized sonication protocols and blinded imaging review, UTMD could upgrade TARE efficacy without added systemic toxicity—watch for durability, transplant/bridging effects, and dosimetry-by-arm analyses before practice shifts.
🔗 https://pubmed.ncbi.nlm.nih.gov/41025990
Cholangiocarcinoma
Dual IDH1/2 inhibitor LY3410738: cytostatic alone; 42% ORR with cis/gem in IDH-mutant cholangiocarcinoma
LY3410738, an oral brain-penetrant inhibitor of mutant IDH1/2, was evaluated in a global Phase 1 (NCT04521686): monotherapy in multiple IDH-mutant solid tumors (n=94) and combinations in cholangiocarcinoma—cisplatin/gemcitabine first-line (n=19) and durvalumab in relapsed/refractory (n=6). No DLTs were observed; common AEs were nausea, vomiting, and appetite loss. Activity was largely cytostatic as monotherapy: ORR 5.2% with DCR 56.9% in R/R IDH-mutant cholangiocarcinoma and ORR 11.1% with DCR 63.0% in IDH1-mutant glioma—similar to the “disease-stabilizing” profile seen with the approved IDH1 inhibitor ivosidenib in previously treated CCA (mPFS 2.7 mo; ORR 2%). In newly diagnosed IDH-mutant cholangiocarcinoma, LY3410738+cis/gem achieved ORR 42.1%, mDOR 8.1 mo, and mPFS 10.2 mo—numerically above historical cis/gem alone (ORR ~26%, mPFS ~8.0 mo, mOS ~11.7 mo), though the combo cohort was small and uncontrolled.
Take Home: Single-agent LY3410738 looks class-consistent (cytostatic) while the first-line cis/gem signal (higher ORR and longer PFS vs ABC-02 benchmarks) justifies a randomized test—ideally against modern SOC (cis/gem±durvalumab) to determine whether dual-IDH blockade adds meaningful benefit beyond chemotherapy.
🔗 https://pubmed.ncbi.nlm.nih.gov/41026608
13 New Trials This Week
🆕 4 First-in-human
🔄 6 Expansion
✅ 3 RegistrationalNSCLC Trials
🏆 SPOTLIGHT: Divarasib (KRAS G12C) + pembrolizumab moves into 1L NSCLC—aims to dethrone chemo-IO.✅ Phase 3 Divarasib (KRAS G12C inhibitor) and Pembrolizumab in Advanced NSCLC
This Phase 3 randomized open-label trial compares an experimental regimen of divarasib (a KRAS G12C inhibitor) plus pembrolizumab with standard pembrolizumab plus chemotherapy (pemetrexed and a platinum agent) in previously untreated adults with advanced non-squamous NSCLC harboring KRAS G12C mutations. The study aims to assess efficacy and safety, marking the first evaluation of divarasib-based combination therapy in this patient population. Roughly 11–13% of NSCLC harbors KRAS G12C; divarasib (Genentech/Roche) seeks to improve on chemo-IO standards.
10 locations (6 US plus locations in Hong Kong and Taiwan) | NCT06793215
Glioblastoma (CNS) Trials
🏆 SPOTLIGHT: GammaTile brachytherapy tests a surgery-room boost for newly diagnosed GBM.✅ Phase 3 Trial: Temozolomide (alkylating agent) and GammaTile (brachytherapy) in GBM
This Phase 3 randomized, open-label study by GT Medical Technologies evaluates standard resection with EBRT and temozolomide versus resection plus GammaTile implantation followed by abbreviated EBRT with the same temozolomide regimen in newly diagnosed, resectable glioblastoma (IDH-mutant and IDH-wt). The goal is to see if adding GammaTile at the time of surgery improves outcomes over today’s standard (maximal safe resection → chemoradiation with temozolomide) by delivering radiation directly to the resection cavity margins in the OR. Prior GammaTile studies suggested practical benefits: radiation starts immediately in the OR (avoiding the usual 4–6-week post-op wait), focuses dose at the edges where GBM recurs while limiting exposure to nearby brain, and can shorten the EBRT course— with small GBM cohorts reporting encouraging local control and acceptable toxicity. This Phase 3 is designed to confirm those signals.
Tempe, AZ | NCT07195591
🆕 Phase 1 MT-125 Trial: NMII Inhibitor in Glioblastoma with Radiotherapy
This Phase 1 study is assessing MT-125, a non-muscle myosin II (NMII) paralogs IIA and IIB directed small molecule inhibitor, administered with radiotherapy to determine its safety and optimal dosing in newly diagnosed, IDH wild-type, MGMT-unmethylated glioblastoma patients. Conducted by Myosin Therapeutics Inc., the dose escalation and randomized expansion trial is a first-in-human investigation aiming to enhance radiotherapy effectiveness in a challenging brain tumor population. Today’s standard for this subgroup remains chemoradiation with poor prognosis; MT-125 (Myosin Therapeutics) explores radiosensitization to shift that baseline with a new first-in-class drug.
Phoenix, AZ; Jacksonville, FL; and Rochester, MN | NCT07185880
Prostate Cancer Trial
🏆 SPOTLIGHT: Pasritamig (KLK2×CD3) bispecific goes pivotal in post-ARPI mCRPC.✅ Phase 3 Pasritamig T cell redirecting bispecific antibody targeting KLK2 and CD3
This Phase 3 study, sponsored by Janssen Research & Development, evaluates overall survival in metastatic castration-resistant prostate cancer after ARPIs (and often taxanes), using a randomized, double-blind, placebo-controlled design of step-up IV pasritamig plus best supportive care (may include chemotherapy) versus placebo plus best supportive care. The aim is to add a chemo-free immune option beyond cabazitaxel, selected PARP inhibitors, or radioligands. Earlier Phase 1 data showed a manageable safety profile (CRS <10%, all Grade 1 with step-up dosing) and signals of activity in heavily pretreated mCRPC: PSA50 declines in ~42% of patients, objective response rate ~8%, and median radiographic PFS around 7.9–7.85 months, supporting progression to Phase 3.
12 locations (8 US and 4 in Australia) | NCT07164443
Colorectal Cancer Trial
🔄 Phase 1 Doxorubicin (DNA intercalator) microdevice trial in colorectal liver metastases
This prospective Phase 1 study by Northwell Health evaluates the safety and feasibility of a percutaneously implanted microdevice loaded with chemotherapeutic agents—including doxorubicin (DNA intercalator), FOLFOX (platinum-based regimen), and immune modulators—to assess localized drug diffusion in patients with colorectal liver metastases. The device is placed 3–5 days before planned tumor resection and retrieved en bloc to examine tissue response without increased post-operative complications. Today’s standard for resectable liver mets is peri-operative systemic therapy plus surgery; this microdevice approach probes in-patient drug sensitivity to tailor systemic choices.
Lake Success, NY | NCT07193862
Bladder Cancer Trial
🔄 Phase 2 UroAmp Diagnostic for utDNA Biomarker Detection in NMIBC
This clinical trial led by Lahey Clinic is evaluating the UroAmp test—a molecular diagnostic that detects tumor DNA alterations—to guide less frequent cystoscopy in high-risk, post-BCG non–muscle invasive bladder cancer patients. Participants are randomized to a de-intensified surveillance arm incorporating the genomic test or a standard follow-up arm, aiming to safely reduce invasive procedures while monitoring disease status. In routine care, high-risk NMIBC relies on intensive cystoscopic surveillance after BCG; this study tests UroAmp (Convergent Genomics) to safely space scopes without missing recurrences.
Burlington, MA | NCT07187063
Sarcoma Trial
🔄 Phase 2 Zanzalintinib Trial: cMet and VEGFR Inhibitor in Advanced Bone Sarcomas
This Phase 2 study at MD Anderson evaluates zanzalintinib monotherapy in cohorts of patients with advanced or metastatic bone sarcomas, including chondrosarcoma, osteosarcoma, and Ewing sarcoma. Zanzalintinib inhibits cMet and VEGFR to target angiogenesis and tumor growth while assessing efficacy in first- to third-line or no standard-of-care settings. Standard options are surgery/RT and multi-agent chemo with limited later-line activity; zanzalintinib (Exelixis) explores anti-angiogenic control in these rare sarcomas.
Houston, TX | NCT07193550
Multiple Myeloma Trial
🔄 Phase Ib NT-I7 Trial: IL-7 Fusion Protein Enhancing BCMA CAR-T Cell Persistence
Investigators at Washington University School of Medicine are conducting a double-blind, placebo-controlled Phase Ib study to evaluate NT-I7, a recombinant IL-7 fusion protein designed to boost CAR-T cell expansion when combined with standard BCMA CAR-T (Cilta-cel) in patients with relapsed/refractory multiple myeloma. The trial randomizes patients to either NT-I7 or placebo and monitors safety, toxicity, and immune cell persistence through correlative analyses. Today’s care after BCMA therapy includes bispecifics/CAR-T re-treatment or triplet/quadruplet salvage; NT-I7 (NeoImmuneTech) aims to extend CAR-T persistence on that backdrop.
St. Louis, MO | NCT07200089
Solid Tumor Trials
🏆 SPOTLIGHT: First-in-human dual-target ADC (AVZO-103; Nectin-4/Trop-2) opens access in urothelial/solid tumors.🆕 Phase 1/2 AVZO-103 Nectin4/Trop2 ADC trial in advanced urothelial and solid tumors
This first clinical trial sponsored by Avenzo Therapeutics evaluates the safety, tolerability, pharmacokinetics, and antitumor activity of AVZO-103 in patients with locally advanced or metastatic urothelial cancer and other solid tumors. The study uses an intravenous antibody-drug conjugate that links a unique undisclosed toxin to Nectin4 and Trop2 targets, administered as both monotherapy and in combination to determine the maximum tolerated dose and potential efficacy. Nectin-4 is highly prevalent in urothelial carcinoma (~90%) and Trop-2 is widely expressed across epithelial tumors; AVZO-103 (Avenzo Therapeutics) taps both to widen eligibility.
Austin, TX | NCT07193511
🏆 SPOTLIGHT: First-in-human RBM39 degrader (ST-01156) brings targeted protein degradation to solid tumors🆕 Phase 1/1B study of ST-01156, a small molecule RBM39 degrader
This open-label trial led by SEED Therapeutics investigates escalating doses of orally administered ST-01156—an RBM39 degrader targeting RNA-binding motif protein 39—in patients with advanced, unresectable, measurable solid tumors. The study examines safety, tolerability, and optimal dosing using a regimen of daily administration for 5 days followed by 2 drug-free days per 7-day cycle, representing a first-in-human exploration of this novel mechanistic approach in oncology. Most late-line care is cytotoxic/targeted/IO by histology; ST-01156 (SEED Therapeutics) introduces a targeted protein degradation strategy.
Duarte and Newport Beach, CA; Boston, MA; New York, NY; Houston, TX | NCT07197554
🆕 Phase 1 DS9051b novel steroidogenesis inhibitor trial in ACC and mCRPC
This Phase 1 first-in-human trial is evaluating the safety, tolerability, and preliminary efficacy of DS9051b—a novel steroidogenesis inhibitor—in participants with advanced/metastatic adrenocortical carcinoma and metastatic castration-resistant prostate cancer who have progressed on prior androgen receptor pathway inhibitors. The open-label, multicenter study by Daiichi Sankyo seeks to establish a recommended dose while exploring pharmacodynamics and early antitumor activity. Eligible patients include those with progressive mCRPC and advanced or metastatic ACC. In practice, post-ARPI mCRPC and metastatic ACC have limited endocrine options; DS9051b (Daiichi Sankyo) probes a new hormonal axis.
6 locations (Florida, New York, and Rhode Island, plus France and the UK) | NCT07189403
🔄 Phase 1 TR-002 bisaminoquinoline tumor growth inhibitor in advanced solid tumors
This trial led by University of California, Davis is evaluating the safety, tolerability, and optimal dose of TR-002—a bisaminoquinoline derivative that likely interferes with tumor cell division—and nadofaragene firadenovec, an adenovirus gene therapy delivering IFN-alpha2b to stimulate an anti-tumor immune response. The study enrolls patients with advanced, unresectable, or metastatic solid tumors and refractory pancreatic adenocarcinoma, with detailed monitoring through imaging and cardiac assessments during 28-day infusion cycles. Usual later-line care is cytotoxic/IO by histology; TR-002 with IFN-α gene therapy (FerGene/Ferring for nadofaragene) tests an immune-stimulatory pairing.
Sacramento, CA | NCT07189195
🔄 Phase 1 Pilot: Pafolacianine, Folate Receptor–Directed Fluorescent Imaging Agent
This investigator initiated study evaluates whether Pafolacianine, a folate receptor–directed fluorescent imaging agent, can enhance intraoperative tumor visualization during surgical debulking of solid tumors. The single arm trial enrolls adults with suspected gastrointestinal, foregut, pancreatic, hepatobiliary, esophageal, and gynecologic malignancies planned for resection or HIPEC/debulking. Over approximately two months, participants receive the study drug prior to surgery with near‐infrared imaging used to assess tissue fluorescence. In the OR, surgeons rely on visual inspection and margin assessment; pafolacianine (On Target Labs/CYTALUX) aims to light up tumor to improve resections.
Dallas, TX | NCT07039526
This summary is produced by Sagely Health.
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