Audio Journal of Oncology Podcast

An interview with: Christof Vulsteke MD PhD, Medical Oncologist, Head of the Integrated Cancer Center Ghent, Belgium BERLIN, Germany—Patients with muscle invasive bladder who were ineligible for cisplatin chemotherapy gained large, clinically meaningful and statistically significant benefits from treatment with the antibody drug conjugate enfortumab vedotin combined with pembrolizumab checkpoint inhibition in the phase three KEYNOTE-905 study. At the 2025 Annual Congress of the European Society for Medical Oncology (ESMO) Medical Oncologist Christof Vulsteke, Head of the Integrated Cancer Centre in Ghent, Belgium, reported marked improvements of event-free and overall survival among patients treated with the new combination, in comparison with those receiving standard radical cystectomy plus pelvic lymph node dissection. After his talk in Berlin he gave more details to Audio Journal of Oncology reporter Peter Goodwin: Audio Journal of Oncology: Christof Vulsteke MD PhD; IN: “[GOODWIN] I am at the ESMO meeting in Berlin ……OUT: …Goodwin for the Audio Journal of Oncology, Goodbye 7:12 secs ESMO 2025 ABSTRACT No. LBA2 “Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study” Speaker: Christof Vulsteke (Gent, Belgium) Authors: Christof Vulsteke (Gent, Belgium) Hristos Kaimakliotis (Indianapolis, United States of America) Pongwut Danchaivijitr (Bangkok, Thailand) Maksym Y. Sabadash (Lviv, Ukraine) Alejo Rodriguez-Vida (Barcelona, Spain) Zhentao Zhang (Fort Wayne, United States of America) Vagiz Atduev (Nizhny Novgorod, Russian Federation) Yunus Emre Goger (Konya, Türkiye) Steffen Rausch (Tuebingen, Germany) Seok Ho Kang (Seoul, Republic of Korea) Yohann Loriot (Villejuif, France) Jens Bedke (Stuttgart, Germany) Matthew D. Galsky (New York, United States of America) Peter H. O’Donnell (Chicago, United States of America) Michael Mihm (Chicago, United States of America) Changting Meng (Groton, United States of America) David Huang (Rahway, United States of America) Chethan Ramamurthy (North Wales, United States of America) Blanca Homet Moreno (Madrid, Spain) Anders Ullén (Stockholm, Sweden) Background Radical cystectomy + pelvic lymph node dissection (RC + PLND) is the standard treatment for pts with MIBC who are cisplatin-ineligible. Periop therapy may improve outcomes in these pts. Methods The phase 3 KEYNOTE-905/EV-303 study (NCT03924895) evaluated efficacy and safety of periop EV + pembro and RC + PLND vs RC + PLND in adult pts with MIBC (T2-T4aN0M0 or T1-T4aN1M0) who were cisplatin-ineligible or declined cisplatin. Pts were randomized 1:1 to EV + pembro (3 cycles EV 1.25 mg/kg on d1 and d8 + pembro 200 mg on d1 Q3W, followed by RC + PLND, then 6 cycles EV + 14 cycles pembro) vs control (RC + PLND only). Study therapy continued until progression, unacceptable adverse events (AEs), withdrawal of consent, or completion of planned treatment. The primary endpoint was event-free survival (EFS) by blinded independent central review. Secondary endpoints were overall survival (OS; key), pathological complete response (pCR) rate (key), and safety. Results 170 pts were randomized to EV + pembro and 174 pts to control. >80% of pts were cisplatin-ineligible per Galsky criteria. As of Jun 6, 2025, median follow-up time was 25.6 mo (range, 11.8–53.7). 149 pts (87.6%) in the EV + pembro arm and 156 (89.7%) in the control underwent surgery. EV + pembro significantly improved EFS (median not reached [NR] vs 15.7 mo; HR 0.40; 95% CI 0.28–0.57; P<.001), OS (NR vs 41.7 mo; HR 0.50; 95% CI 0.33–0.74; P<.001), and pCR rate (57.1% vs 8.6%; estimated difference 48.3%; 95% CI 39.5–56.5; P<.001) vs control. Treatment-emergent AEs occurred in 100% (gr ≥3, 71.3%) of pts in the EV + pembro arm and 64.8% (gr ≥3, 45.9%) in the control. Most frequent gr ≥3 AE of special interest (based on distinct prespecified lists for each drug) was severe skin reactions (grouped term; 11.4%) for pembro, and skin reactions (grouped term; 10.8%) for EV. Conclusions Adding periop EV + pembro to surgery significantly and meaningfully improved EFS, OS, and pCR rate in pts with MIBC who were predominantly cisplatin-ineligible. The safety profile of EV + pembro was manageable and consistent with prior reports. This is the first perioperakthrough regimen to improve outcomes vs RC + PLND in this setting and may be a new standard of care. Clinical trial identification: NCT03924895.

An interview with: Xichun Hu MD PhD, Professor, Director, Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China BERLIN, Germany—In a head-to-head comparison of two antibody drug conjugates used to treat unresectable or metastatic breast cancer, patients treated with trastuzumab botidotin lived more than twice as long before disease progression than those in the control arm receiving trastuzumab emtansine (T-DM1). This finding was announced by Chinese researchers at the 2025 Annual Congress of the European Society of Medical Oncology. Lead author Xichun Hu MD PhD, Professor, Director, Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China talked about the findings of his groups phase three randomized controlled study with Audio Journal of Oncology reporter Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Xichun Hu MD PhD IN: “[GOODWIN] Peter Goodwin at ESMO ..OUT: ..of Oncology, I’m Peter Goodwin 8:30 sec ESMO ABSTRACT LBA24 “Trastuzumab botidotin vs trastuzumab emtansine (T-DM1) in HER2-positive unresectable or metastatic breast cancer: Results from a randomized phase III study” Speaker: Xichun Hu (Shanghai, China) Authors: Xichun Hu (Shanghai, China) Jian Zhang (Shanghai, China) Quchang Ouyang (Changsha, China) Qingyuan Zhang (Harbin, China) Huihui Li (Jinan, China) Xu Wang (Tianjin, China) Ying Wang (Guangzhou, China) Yongmei Yin (Nanjing, China) Shusen Wang (Guangzhou, China) Yuanting Gu (Zhengzhou, Algeria) Tao Sun (Shenyang, China) Jingfen Wang (Linyi, China) Xinhong Wu (Wuhan, China) Fanfan Li (Hefei, China) Xi Chen (Fuzhou, China) Man Li (Dalian, China) Jin Yang (Xi’an, Shaanxi Province, China) Hua Yang (Baoding, China) Xiaoping Jin (Chengdu, China) Junyou Ge (CHENGDU, China) Lecture Time ASTRACT Background Trastuzumab botidotin (A166) is a HER2-directed ADC developed using a stable, protease-cleavable valine-citrulline linker conjugated to the anti-microtubule agent Duo-5. In a phase 1 study, A166 showed promising activity in heavily pretreated patients (pts) with HER2+ breast cancer (BC). Here, we first report the results from a phase 3 study (NCT06968585).   Methods Pts with HER2+ unresectable or metastatic BC who had received at least one prior anti-HER2 therapy were randomized (1:1) to receive A166 (4.8 mg/kg Q3W) or T-DM1 (3.6 mg/kg Q3W) until disease progression or unacceptable toxicity. The primary endpoint was PFS by BICR per RECIST v1.1.   Results A total of 365 pts were randomized (median age 55 years; 73.4% with visceral metastases; 53.4% received ≥2 prior anti-HER2 therapies; 55.9% had prior pyrotinib). As of 26 April 2025, median follow-up was 14.9 mo. Median PFS was significantly longer in A166 than in T-DM1 (11.1 mo vs 4.4 mo; HR 0.39 [95% CI 0.30-0.51], p<0.0001). PFS benefit with A166 was consistently observed regardless of prior lines of anti-HER2 therapy (HR 0.36 for 1 prior line; HR 0.39 for ≥2 prior lines). ORR by BICR was 76.9% vs 53.0%, and mDOR was 12.2 mo vs 5.7 mo. Although OS data were immature, a trend toward benefit was observed in A166 (HR 0.62; 95% CI, 0.38-1.03). Grade ≥3 TEAEs occurred in 69.8% of pts in A166 and 63.7% in T-DM1. The most common grade ≥3 TEAEs (≥5%) were corneal disorder, dry eye, and vision blurred in A166, and platelet count decreased, neutrophil count decreased, hypokalemia, and GGT increased in T-DM1. Among A166-treated pts who experienced any-grade ocular AEs, instrumental activities of daily living (ADL) limitations occurred in 37 (20.3%) pts, and self-care ADL limitations in 13 (7.1%) pts; these resolved in 32 (86.5%) and 12 (92.3%) pts, respectively. TEAEs led to discontinuation in 1.1% of pts in A166 and 3.8% in T-DM1. No TEAE led to death in A166, compared with 1.1% in T-DM1. Conclusions A166 demonstrated statistically significant and clinically meaningful improvement in PFS compared with T-DM1, with a manageable safety profile in pts with HER2+ unresectable or metastatic BC. These results position A166 as a potential new therapeutic option for HER2+ disease. Clinical trial identification NCT06968585. Legal entity responsible for the study Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Funding Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Disclosure Jin, J. Ge: Financial Interests, Institutional, Full or part-time Employment: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. All other authors have declared no conflicts of interest. Xichun Hu MD, PhD Medical Oncology Xuhui, Shanghai, China Xi-Chun Hu, M.D., Ph. D., is currently a Professor, Director of the Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China. Dr. Hu has published more than 170 papers in the journals, such as Lancet Oncology, JCO, and International Journal Cancer, and 5 book chapters. He is vice editor of the ABC (Advanced breast cancer) guideline (Chinese version) and one of the leading authors of the CBCS (Chinese Breast Cancer Society) guideline for

An interview with: Martin Wermke MD, TU Dresden, NCT/UCC Early Clinical Trial Unit and Medical Clinic, Poliklinik I, Natural Centre for Tumor Diseases, Dresden, Germany BERLIN, Germany—The prospect of markedly better outcomes for patients with small cell lung cancer, with “encouraging initial survival outcomes”, was raised by findings from the DeLLphi-303 study, reported at the European Society for Medical Oncology (ESMO) 2025 Annual Congress. The bi-specific T-cell engager drug tarlatamab was included with initial therapy for patients with extensive stage small cell lung cancer. Martin Wermke MD, from TU Dresden, Director of the NCT/UCC Early Clinical Trial Unit and of the Medical Clinic, Poliklinik I, Natural Centre for Tumor Diseases in Dresden, Germany reported the latest study data to the ESMO congress. After his talk he gave the details to our reporter Peter Goodwin: Audio Journal of Oncology; Martin Wermke MD: ”[GOODWIN] Peter Goodwin here at the ESMO meeting ………….of Oncology, I’m Peter Goodwin.” 6:16secs https://pubmed.ncbi.nlm.nih.gov/40934933/ ESMO ABSTRACT 2757O Tarlatamab with first-line chemoimmunotherapy for extensive stage small cell lung cancer (ES-SCLC): DeLLphi-303 study Speaker: Martin Wermke (Dresden, Germany) Authors Martin Wermke (Dresden, Germany) Sally Lau (Toronto, Canada) Mor T. Moskovitz (Petah Tikva, Israel) Ingel Demedts (Roeselare, Belgium) Kelly Paulson (Seattle, United States of America) Aurélie Swalduz (Lyon, France) Cornelius Waller (Freiburg, Germany) Luis Paz-Ares (Madrid, Spain) Makoto Nishio (Koto-ku, Japan) Michael Boyer (Camperdown, Australia, NSW) James Chih-Hsin Yang (Taipei City, Taiwan) Amanda Parkes (Thousand Oaks, United States of America) Yuyang Zhang (Thousand Oaks, United States of America) Ali Hamidi (Thousand Oaks, United States of America) Mukul Minocha (Thousand Oaks, United States of America) Pedro F. Simoes da Rocha (Barcelona, Spain) Background: Tarlatamab with anti-PD-L1 achieved notable survival outcomes with manageable safety as maintenance therapy following 1L platinum-etoposide chemotherapy and anti-PD-L1 (1L chemo-IO) for ES-SCLC. In this phase Ib study (parts 2, 4, 7), the safety and efficacy of adding tarlatamab to 1L chemo-IO was assessed. Methods: Patients (pts) had received 1 cycle of 1L chemo-IO prior to enrollment. On study, pts received 3 cycles of tarlatamab + 1L chemo-IO followed by tarlatamab + anti-PD-L1 Q3W until progression. Tarlatamab was administered 20 mg Q3W with a 1 mg step dose. Primary endpoints included dose-limiting toxicities (DLTs), treatment-emergent (TE), and treatment-related (TR) adverse events (AEs). Key secondary endpoints were objective response (OR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Of 96 pts enrolled, 3 (3%) had DLTs. TEAEs and TRAEs were reported in all pts. The most common TRAEs were cytokine release syndrome (CRS, 56%), anemia (54%), and dysgeusia (46%). Grade (Gr) ≥ 3 TRAEs occurred in 72 pts (75%), most commonly neutropenia/neutrophil count decreased (44%), anemia (23%), and lymphopenia/lymphocyte count decreased (11%), primarily within the first two cycles. CRS (54% Gr 1-2; 2% Gr 3-4) and ICANS and associated neurological events (5% Gr 1-2; 1% Gr 3) TRAEs were mostly low grade. Other immune-related AEs were rare (2%). From a baseline scan after 1 cycle of 1L chemo-IO, OR rate following tarlatamab addition to 1L chemo-IO was 71%, with median DOR of 11.0 months (mo) (95% CI 6.7-not estimable). Median PFS was 9.0 mo. With a median follow-up time of 11.3 mo, the Kaplan-Meier estimate of OS at 12 mo was 81% (Table). Results from further follow-up will be presented. Table: 2757O Safety and efficacy of tarlatamab + chemoimmunotherapy as 1L treatment for ES-SCLC Conclusions: The combination of tarlatamab with chemo-IO for 1L treatment of ES-SCLC demonstrated manageable safety with encouraging initial survival outcomes, supporting further investigation of this combination in the phase III DeLLphi-312 study. Clinical trial identification: NCT05361395. Editorial acknowledgement Medical writing support for the development of this abstract was provided by Sukanya Raghuraman, PhD, of Cactus Life Sciences, part of Cactus Communications, and Liz Leight, PhD, an employee of Amgen Inc., and was funded by Amgen Inc. Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc.

An interview with: John P. Crown MD MBA, Consultant Medical Oncologist, St. Vincent’s University Hospital, Dublin, Professor of Translational Cancer Research, Dublin City University, Professor of Medicine, University College Dublin Ireland. BERLIN, Germany—Patients with high-risk node-negative ER-positive HER2-negative early breast cancer who had the CDK 4/6 inhibitor drug ribociclib added to their non-steroidal aromatase inhibitor (AI) adjuvant therapy after surgery had significantly longer freedom from progression to invasive disease compared with patients receiving the AI alone. This is according to five-year data from the NATALEE trial reported at the 2025 Annual Congress of the European Society for Medical Oncology. Professor John P. Crown MD MBA, Consultant Medical Oncologist, from St. Vincent’s University Hospital in Dublin gave reporter Peter Goodwin the latest details: Audio Journal of Oncology, John P. Crown MD MBA, IN: “[GOODWIN] I am at the ESMO meeting, 2025, in Berlin ….OUT: signing off for the Audio Journal of Oncology.” 11:24 secs 2025 ESMO: Proffered Paper Friday 14:00 Oct 17, 2025 Abstract Title: LBA14 – Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC): NATALEE 5-year outcomes Speaker: John P. Crown (Dublin, Ireland) Authors: John P. Crown (Dublin, Ireland) Daniil Stroyakovskiy (Moscow, Russian Federation) Denise Yardley (Chattanooga, United States of America) Chiun-Sheng Huang (Taipei City, Taiwan) Peter A. Fasching (Erlangen, Germany) Aditya Bardia (Los Angeles, United States of America) Stephen Chia (Vancouver, Canada) Seock-Ah Im (Seoul, Republic of Korea) Miguel Martin (Madrid, Spain) Binghe Xu (Beijing, China) Carlos H. Barrios (Porto Alegre, Brazil) Michael Untch (Berlin, Germany) Rebecca Moroose (Lake Mary, United States of America) Sara A. Hurvitz (Seattle, United States of America, CA) Gabriel N. Hortobagyi (Houston, United States of America) Dennis Slamon (Los Angeles, United States of America) Frances Visco (Washington, United States of America) Gonzalo Spera (Montevideo, Uruguay) Zheng Li (East Hanover, United States of America) Sherene Loi (Melbourne, Australia, VIC) Background: The phase 3 NATALEE trial demonstrated that adjuvant RIB + NSAI led to a statistically significant invasive disease–free survival (iDFS) benefit in pts with stage II and III HR+/HER2− EBC. We present a protocol-specified 5-year efficacy analysis. Methods: Pts with HR+/HER2− EBC were randomized 1:1 to RIB (400 mg/d; 3 weeks on/1 week off for 3 y) + NSAI (letrozole 2.5 mg/d or anastrozole 1 mg/d for 5 y) or NSAI alone. Men and premenopausal women received goserelin. Pts were included if they had anatomical stage IIA (if N1 [1-3 axillary lymph nodes] or N0 with additional high-risk factors), stage IIB, or stage III disease per AJCC, 8th ed. The primary end point of iDFS and secondary efficacy end points of distant disease–free survival (DDFS), distant relapse–free survival (DRFS), and overall survival (OS) were evaluated using Kaplan-Meier methods. Statistical comparisons were made by stratified log-rank test. Results: At data cutoff (May 28, 2025), all pts were off RIB treatment, and a similar proportion had completed 5 years of NSAI treatment in both arms (RIB + NSAI, 36.5%; NSAI alone, 34.4%). With a median iDFS follow-up of 55.4 months, RIB + NSAI demonstrated persistent iDFS benefit over NSAI alone (hazard ratio [HR], 0.716; 95% CI: 0.618-0.829; nominal 1-sided P<.0001). Absolute iDFS rates were 90.8% vs 88.0% at 3 y, 88.3% vs 83.9% at 4 y, and 85.5% vs 81.0% at 5 y (absolute improvement of 2.7%, 4.4%, and 4.5%, respectively). iDFS benefit was observed across subgroups, including N0 (HR, 0.606; 95% CI: 0.372-0.986). RIB + NSAI also demonstrated continued DDFS (HR, 0.709; 95% CI: 0.608-0.827) and DRFS (HR, 0.699; 95% CI: 0.594-0.824) benefit vs NSAI alone. A positive trend for OS favoring RIB + NSAI (HR, 0.800; 95% CI: 0.637-1.003; nominal 1-sided P=.026) continues to emerge. No new safety signals were observed with a median follow-up time of approximately 2 years after RIB completion. Conclusions: In this 5-year landmark analysis with mature efficacy data, RIB + NSAI reduced the risk of invasive and distant disease recurrence compared with NSAI alone, including in pts with high-risk N0 disease. A positive trend for OS in favor of RIB + NSAI continues to emerge.

An interview with: Javier C Cortés MD PhD, Breast Cancer Medical Oncologist, IOB Madrid, Institute of Oncology, Madrid, and International Breast Cancer Centre, Barcelona, Spain BERLIN, Germany—Treatment with the antibody drug conjugate (ADC) sacituzumab govitecan (that targets the Trop-2 cancer-associated protein, delivering a cytotoxic topoisomerase inhibitor payload) has significantly improved progression-free survival in patients with newly-diagnosed metastatic triple-negative breast cancer who were not candidates for treatment with immune checkpoint inhibition and had received no prior therapy. At the European Society for Medical Oncology (ESMO) 2025 Annual Congress Javier C Cortés MD PhD from the Institute of Oncology in Madrid and the International Breast Cancer Centre in Barcelona reported data from the ASCENT-03 study showing that treatment with sacituzumab govitecan brought clinically meaningful benefits with toxicities that were found to be manageable. At the congress Cortés talked about the new findings with Peter Goodwin: Audio Journal of Oncology: Javier C Cortes MD PhD “[GOODWIN] Peter Goodwin here in Berlin …..……….Audio Journal of Oncology, I’m Peter Goodwin. 9:47secs ESMO ABSTRACT: LBA20 – “Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i)” Speaker: Javier C. Cortés (Barcelona, Spain) Authors: Javier C. Cortés (Barcelona, Spain), Aditya Bardia (Los Angeles, United States of America), Kevin Punie (Antwerp, Belgium), Carlos H. Barrios (Porto Alegre, Brazil), Sara A. Hurvitz (Seattle, United States of America, CA),Andreas Schneeweiss (Heidelberg, Germany), Joohyuk Sohn (Seoul, Republic of Korea), Eriko Tokunaga (Fukuoka, Japan), Adam M. Brufsky (Pittsburgh, United States of America, PA), Yeon Hee Park (Seoul, Republic of Korea), Binghe Xu (Beijing, China), Roberto Hegg (São Paulo, Brazil), Mafalda Oliveira (Barcelona, Spain), Alessandra Fabi (Rome, Italy), Natalya Vaksman (Miami, United States of America), Theresa Valdez (Miami, United States of America), Xinrui Zhang (Miami, United States of America), Catherine Lai (Foster City, United States of America, CA), Sara M. Tolaney (Boston, United States of America, MA) Background Significant PFS benefit was observed with SG vs chemo in pretreated metastatic (m)TNBC (ASCENT) and with SG + pembrolizumab vs chemo + pembrolizumab in first-line (1L) PD-L1+ mTNBC (ASCENT-04). For pts with mTNBC who cannot receive PD-(L)1i, treatment options are limited. We report primary results from the randomized phase 3 ASCENT-03 study (NCT05382299) of 1L SG vs chemo in pts with locally advanced unresectable or mTNBC who are unable to receive a PD-(L)1i. Methods Pts had centrally confirmed PD-L1− mTNBC (defined as combined positive score [CPS] < 10) or PD-L1+ mTNBC (CPS ≥ 10) but were unable to receive PD-(L)1i due to a comorbidity or prior use in the curative setting. Randomization (1:1) to SG (10 mg/kg IV, days 1 & 8 in 21-day cycles) or chemo (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin) was stratified by disease status and geography. The primary end point was PFS by BICR. Key secondary end points included overall survival (OS), ORR and DOR by BICR, and safety. Results 558 pts (279 in each group) with mTNBC were randomized. With a median follow-up of 13.2 mo, SG showed a significant improvement in median PFS vs chemo (9.7 vs 6.9 mo; HR, 0.62; 95% CI, 0.50-0.78; P < .0001); median DOR was 12.2 mo vs 7.2 mo (Table). OS data were immature. The most frequent grade ≥ 3 TEAEs were neutropenia (43%) and diarrhea (9%) with SG and neutropenia (41%) and anemia (16%) with chemo. Conclusions SG led to a statistically significant and clinically meaningful improvement in PFS and more durable responses vs chemo in 1L mTNBC. The safety profile of SG was manageable and consistent with its known profile; treatment discontinuation rate due to TEAEs was lower with SG vs chemo. These data support SG as a potential new standard of care for pts with previously untreated mTNBC who are unable to receive a PD-(L)1i. Table: LBA20 Clinical trial identification NCT05382299. Editorial acknowledgement Editorial assistance was provided by Peggy Robinet, PharmD, PhD, and Sonal S. Joshi, PhD, of Parexel, and funded by Gilead Sciences, Inc. Legal entity responsible for the study Gilead Sciences, Inc. Funding Gilead Sciences, Inc. PRESS RELEASE: ASCENT-03: Trodelvy® Demonstrates Highly Statistically Significant & Clinically Meaningful Improvement in Progression Free Survival in Patients With First-line Metastatic Triple-Negative Breast Cancer Who Are Not Candidates for Checkpoint Inhibitors – Second Positive Phase 3 Trial in First-line Metastatic TNBC Where Trodelvy Has Demonstrated a Clinically Meaningful Benefit Versus Standard of Care Chemotherapy – – Trodelvy Has

    An interview with: Trevor Leong MD, Peter McCallum Cancer Centre, Radiation Oncology Department, Melbourne, Australia BARCELONA, Spain—Although pre-operative radiotherapy brought better response rates in patients resected for their gastric or GE-junction adenocarcinomas, there was no improvement in survival. This is the clear finding from a big, long-term study led by an Australian team. The multi-continent, phase-three randomized TOP GEAR trial, headquartered in Sydney Australia, definitively found no benefit for overall or progression-free survival from adding radiation before surgery. This clear finding was announced at the 2024 Annual Meeting of the European Society for Medical Oncology (ESMO), held in Barcelona, Spain First author Trevor Leong MD, from the Radiation Oncology Department of the Peter McCallum Cancer Centre in Melbourne Australia, talked about the results with Peter Goodwin: Trevor Leong MD interview (8mins 37 secs): IN: “Resectable gastric or gastro-esophageal…. OUT: ,,’till next time, Good-bye.” ESMO 2024, Barcelona, ABSTRACT: 03880-8/fulltext “A randomised phase three trial of perioperative chemotherapy (CT) with or without pre-operative chemoradiotherapy (CRT) for resectable gastric cancer (AGITG TOPGEAR). Final results from an intergroup trial of AGITG, TROG, EORTC and CCTG”. NEJM September 13, 2024: https://www.nejm.org/doi/full/10.1056/NEJMoa2405195 TITLE: “Preoperative Chemoradiotherapy for Resectable Gastric Cancer” From: The Australasian Gastro-Intestinal Trials Group, National Health and Medical Research Council Clinical Trials Centre, Trans-Tasman Radiation Oncology Group, European Organisation for Research and Treatment of Cancer, and Canadian Cancer Trials Group. JOURNAL Article: N Engl. J Med.: “The addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma.” “A randomised phase three trial of perioperative chemotherapy (CT) with or without pre-operative chemoradiotherapy (CRT) for resectable gastric cancer (AGITG TOPGEAR). Final results from an intergroup trial of AGITG, TROG, EORTC and CCTG”. Background In Western countries, the current standard of care for resectable gastric cancer is periop CT. There is much interest in preop CRT, but comparison to periop CT alone is lacking. In TOPGEAR we hypothesized that adding preop CRT to periop CT would improve pathological complete response (pCR) rates and ultimately overall survival (OS) compared to periop CT alone. Methods This international phase 3 trial randomized patients with resectable adenocarcinoma of the stomach and gastro-esophageal junction to periop CT alone, or with preop CRT. The periop CT alone group received 3 cycles of epirubicin/cisplatin/5-fluorouracil (ECF) or 4 cycles of fluorouracil/leucovorin/oxaliplatin/docetaxel (FLOT) both pre- and post-operatively. The preop CRT group received one less cycle of preop chemotherapy followed by chemoradiotherapy (45 Gy in 25 fractions radiation plus infusional 5-FU ), and then the same postop chemotherapy. The primary endpoint was overall survival, and secondary endpoints included progression free survival (PFS), pCR rates, toxicity and quality of life. Results Between September 2009 and May 2021, 574 patients were enrolled from 70 sites across 15 countries in Australasia, Europe, and Canada; 288 to periop CT group and 286 to preop CRT group. Compared to periop CT alone, patients receiving preop CRT achieved a higher pCR rate (16.7% vs 8.0%), a higher rate of major pathological response (0 – <10% residual tumor: 49.5% vs 29.3%), and greater tumor downstaging following resection. After a median follow-up of 66.7 months, there was no significant difference in OS or PFS: median OS periop CT 49.4 months vs preop CRT 46.4 months; median PFS periop CT 31.8 months vs preop CRT 31.4 months. Preop CRT was not associated with increased perioperative treatment toxicity or a higher rate of surgical complications. Conclusions Despite improving pathological outcomes, the addition of preop CRT to periop CT does not improve overall survival compared to periop CT alone in patients with resectable gastric and gastro-esophageal junction adenocarcinoma. Clinical trial identification ACTRN12609000035224. Registered 30 May 2009; NCT01924819. Legal entity responsible for the study Australasian Gastro-Intestinal Trials Group (AGITG). Funding This work was supported by grants from the National Health and Medical Research Council: 1046425 and 2000711, Canadian Institutes of Health Research (CIHR) grant no. 119445, the Canadian Cancer Society Research Institute (CCSRI) grant no. 021039, the Health Research Council of New Zealand (HRC) International Investment Opportunities Fund: Contract no. 09/624, the EORTC Cancer Research Fund, and the Cancer Australia Priority-driven Collaborative Research Sche

An interview with: Domenica Lorusso MD PhD, Director of the Gynaecological Oncology Unit, full Professor of Obstetrics and Gynaecology, Humanitas Hospital San Pio X, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy. Both overall and progression-free survival were significantly improved when the anti-PD-1 agent pembrolizumab was added to standard chemoradiotherapy as initial treatment for patients with high-risk locally advanced cervical cancer. Results from the randomized, double-blind, phase III KEYNOTE-A18 study of immunotherapy, used together with standard concurrent chemoradiotherapy among 1060 patients, were reported by a multinational team of researchers led from Italy to the 2024 Annual Congress of the European Society for Medical Oncology in Barcelona. The study lead author Domenica Lorusso MD PhD, Director of the Gynaecological Oncology Unit at Humanitas Hospital San Pio X, in Milan, who is a Full Professor of Obstetrics and Gynaecology at Humanitas University, Rozzano, met up with Peter Goodwin to discuss the KEYNOTE-A18 findings. Audio Journal of Onclogy: Domenica Lorusso MD PhD IN: “Immune checkpoint inhibition …..OUT: …….in Barcelona at the ESMO meeting”. Durn: 7:20 secs ESMO Abstract 7090 Lorusso, Gynaecology Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of the Sacred Heart, Rome, Italy “Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, phase III ENGOT-cx11/ GOG-3047/KEYNOTE-A18 study” Background At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945), pembrolizumab (pembro) + concurrent chemoradiotherapy (CCRT) showed a statistically significant and clinically meaningful improvement in PFS vs placebo (pbo) + CCRT in patients (pts) with high-risk locally advanced cervical cancer (LACC). Based on this study, the US FDA has approved pembro + CCRT for pts with FIGO 2014 Stage III-IVA cervical cancer. We present the OS results from the second interim analysis.Methods Eligible pts with newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status) were randomized 1:1 to 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT then brachytherapy. Pts were stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), stage at screening (IB2-IIB vs III-IVA), and planned total radiotherapy dose (<70 Gy vs ≥70 Gy [EQ2D]). Primary endpoints are PFS per RECIST v1.1 by investigator and OS.Results 1060 pts were randomized to pembro + CCRT (n=529) or pbo + CCRT (n=531). At this analysis (January 8, 2024, data cutoff), median follow-up was 29.9 mo (range, 12.8-43.0). Pembro + CCRT showed a statistically significant improvement in OS compared with pbo + CCRT. The 36-mo OS rate was 82.6% with pembro + CCRT vs 74.8% with pbo + CCRT; median OS was NR in either group (HR=0.67 [95% CI, 0.50-0.90]; P=0.0040). The benefit of pembro + CCRT was generally consistent in all prespecified subgroups, including FIGO stages IB2-IIB (HR=0.89 [95% CI, 0.55-1.44]) and III-IVA (HR=0.57 [95% CI, 0.39-0.83]). Grade ≥3 TRAE incidence was 69.1% in the pembro + CCRT group and 61.3% in the pbo + CCRT group. Conclusions Pembro + CCRT showed a statistically significant and clinically meaningful improvement in OS vs pbo + CCRT in pts with high-risk LACC and had a manageable safety profile. These data provide further support for pembro + CCRT as a new standard of care for this population. Clinical trial identification NCT04221945; EudraCT: 2019-003152-37. Editorial acknowledgement Medical writing assistance was provided by Christine McCrary Sisk of Merck & Co., Inc., Rahway, NJ, USA. This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, Audio Journal of Oncology, October 6, 2025    

An interview with: James Larkin FRCP, PhD, Medical Oncologist, Professor, Royal Marsden Hospital, London Checkpoint inhibitor therapy for advanced melanoma has achieved sustained responses and long-term overall survival, transforming the prognosis for as many as half of all patients. 10-year survival outcomes from the phase Ill CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma were reported at the 2024 Annual Meeting of the European Society for Medical Oncology (ESMO) held in Barcelona. Peter Goodwin, talked with study author, James Larkin FRCP PhD, Professor and Medical Oncologist at the Royal Marsden Hospital in London. Audio Journal of Oncology: James Larkin FRCP PhD: IN: “There’s been breath-taking progress ………OUT: join me then, Good-bye!” 14:57secs   SOURCE: Annals of Oncology: https://www.annalsofoncology.org/article/S0923-7534(24)03864-X/fulltext ESMO Abstract LBA43 Larkin, Medicine Department, The Royal Marsden Hospital, London, UK “10-y survival outcomes from the phase Ill CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma” Abstract LBA43 Larkin, Medicine Department, The Royal Marsden Hospital, London, UK “10-y survival outcomes from the phase Ill CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma” Background In CheckMate 067, improved survival with nivolumab plus ipilimumab (NIVO + IPI) or NIVO alone v IPI has been demonstrated in patients (pts) with advanced melanoma. We now provide the final CheckMate 067 results (minimum f/u 10 y), the longest reported in a phase 3 study of an anti–programmed death (PD)-1–based therapy for any tumor type. Methods Pts with untreated advanced melanoma (N = 945) were randomly assigned 1:1:1 and stratified by PD-ligand (L)1 status, BRAF mutation status, and metastasis stage to receive NIVO (1 mg/kg) + IPI (3 mg/kg) Q3W for 4 doses, followed by NIVO (3 mg/kg) Q2W; NIVO (3 mg/kg) Q2W + placebo; or IPI (3 mg/kg) Q3W for 4 doses + placebo until progression or unacceptable toxicity. Co-primary endpoints were OS and PFS with NIVO + IPI or NIVO v IPI; melanoma-specific survival (MSS) was an exploratory endpoint. Results After a 10-y minimum f/u, median OS was 71.9 mo with NIVO + IPI, 36.9 mo with NIVO, and 19.9 mo with IPI. OS HRs were 0.53 (95% CI, 0.44–0.65) with NIVO + IPI vIPI and 0.63 (0.52–0.76) for NIVO v IPI, and benefit was consistent across subgroups (including PD-L1 expression and BRAF mutation status). Median MSS was not reached (NR) with NIVO + IPI (> 120 mo), 49.4 mo with NIVO, and 21.9 mo with IPI. In pts who had PFS for ≥ 3 y, 10-y MSS rates were 96% with NIVO + IPI, 97% with NIVO, and 88% with IPI. Only 8 pts, 4 in the NIVO + IPI arm and 4 in the NIVO arm, progressed beyond 60-mo of f/u. For pts in the NIVO + IPI arm who discontinued treatment during induction due to a treatment-related adverse event, 10-y OS rates were the same as the ITT group (43%) and MSS rates were similar (50% v 52%). Table: LBA43” MORE: James Larkin is a Medical Oncologist specialising in the treatment of cancers of the kidney and skin including melanoma. Professor Larkin grew up in North Cornwall before taking a first in Natural Sciences from Cambridge University. He undertook clinical training in Oxford, qualifying in 1996. His general medical training was undertaken in London and in 2001 he won a Medical Research Council Research Fellowship for a Clinician, carrying out laboratory research leading to a PhD at the Institute of Cancer Research. His specialist training was completed at The Royal Marsden, where he was appointed as a Consultant in 2008. His research is focussed on trying to understand cancer and its consequences better, as well as developing improved treatments, particularly with targeted therapies and immunotherapies. Globally, he is amongst the most highly cited researchers in both melanoma and kidney cancerThis link is external and opens in a new tab. In 2018, he was elected as a Fellow of the Academy of Medical Sciences and in 2020 as an NIHR Senior Investigator. In 2022, he was appointed to roles as Head of The Royal Marsden Skin Unit, Royal Marsden Joint Training Programme Director for Medical Oncology and Lead of the Cancer Immunotherapy Theme at The Royal Marsden / Institute of Cancer Research NIHR Biomedical Research Centre. Since 2024, he has hosted the educational podcast ‘Melanoma Matters’ with his US colleague Professor Sapna Patel, and in 2026 he will be Scientific Co-Chair of the Annual European Society of Medical Oncology meeting in Madrid. Professor Larkin serves as a medical advisor to the patient advocacy group Melanoma UK, as a trustee of Action Kidney Cancer and sits on the Medical Advisory Board of the International Kidney Cancer Coalition.      

An interview with: Jefferson DeKloe BSc, Department of Otolaryngology, Thomas Jefferson University, Philadelphia, PA CHICAGO, USA—Although the take-up of vaccination for human papilloma virus (HPV) among girls and boys in the USA has been lower than in many other industrial countries, American researchers have now shown clearly that in addition to the prevention of cervical cancer in women, men have also been protected against HPV-related cancers. At the 2024 American Society of Clinical Oncology Annual (ASCO) Meeting in Chicago a new study of HPV vaccination of girls and boys in the United States revealed a real-world reduction of oral, plus head and neck cancers in men, as well confirming the prevention of cervical cancers in women, even though uptake of the vaccine in the US had been sub-optimal. The study looked at HPV-associated cancer incidence in a retrospective cohort analysis of patients from the TriNetX Collaborative Network. At the ASACO meeting Peter Goodwin met up with the lead author of the research, Jefferson DeKloe BSc, from the Department of Otolaryngology at Thomas Jefferson University in Philadelphia USA. Audio Journal of Oncology, with: Jefferson DeKloe BSc IN: “HPV Vaccination …..OUT: ……, I’m Peter Goodwin”. 6:00secs https://meetings.asco.org/abstracts-presentations/231759 “Effects of HPV vaccination on the development of HPV-related cancers: A retrospective analysis of a United States-based cohort.” https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.10507 Effects of HPV vaccination on the development of HPV-related cancers: A retrospective analysis of a United States-based cohort. ALSO: https://www.sciencedirect.com/science/article/pii/S1043661825002762 HPV vaccination and malignancy risks beyond cervical cancer: A retrospective global cohort study Authors: Christian Seebauer, Mohamed Faluogy, Peter Sieg , Henning Olbrich, Ralf Ludwig Department of Oral and Maxillofacial Surgery/Plastic surgery, University Medicine Lübeck, Ratzeburger Allee 160, Lübeck 23538, Germany Department of Dermatology, Allergy, and Venerology, University of Lübeck, Ratzeburger Allee 160, Lübeck 23538, Germany Department of Dermatology, Allergy, and Venerology, Institute of Experimental Dermatology, University of Lübeck, Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Ratzeburger Allee 160, Lübeck 23538, Germany Received 28 April 2025, Revised 5 July 2025, Accepted 6 July 2025, Available online 11 July 2025, Version of Record 14 July 2025. HPV vaccination significantly reduced hypopharyngeal and laryngeal cancer risk. Vaccination was associated with a marked decrease in leukemia incidence. No significant protection observed for rectal, anal, or oral cavity cancers. HPV vaccination halved all-cause mortality at 8- and 20-year follow-up. Data support possible HPV involvement in hematopoietic and neuronal tissues. Abstract: While HPV vaccination is well established for the prevention of cervical cancer, its broader oncological effects remain insufficiently characterized. Emerging evidence suggests potential protective effects against non-cervical malignancies; however, comprehensive long-term data are limited. We conducted a global, retrospective cohort study utilizing electronic health records from the TriNetX network. Individuals vaccinated against HPV at age 8 years or older were propensity score-matched to unvaccinated controls. Outcomes included the incidence of malignancies in the head-and-neck, gastrointestinal, anogenital, neuronal, and hematologic systems, as well as all-cause mortality, assessed over 8- and 20-year follow-up periods. Kaplan–Meier survival analysis and hazard ratios (HRs) were employed. HPV vaccination was associated with significant reductions in the risk of hypopharyngeal and laryngeal carcinomas (8-year HR: 0.19; 95 % CI: 0.057–0.631; p = 0.0025; 20-year HR: 0.227; 95 % CI: 0.067–0.764; p = 0.0092) and leukemia (8-year HR: 0.461; p = 0.0035; 20-year HR: 0.443; p = 0.0019). No significant protection was observed for rectal, anal, oral cavity, or prostate cancers. All-cause mortality was reduced by nearly half among vaccinated individuals (8-year HR: 0.543; 20-year HR: 0.536; both p < 0.0001). Beyond epithelial malignancies, HPV vaccination may confer systemic cancer protection, particularly in hematologic and potentially neuronal tissues. These findings suggest a broader biological impact of HPV vaccination than previously recognized and underscore the need for mechanistic studies investigating HPV’s oncogenic pathways. If validated, these results could prompt the expansion of vaccination strategies to encompass broader indications and wider population coverage.            

An interview with Rebecca Dent MD, Deputy Chief Executive Officer, National Cancer Centre, Singapore, ESMO 2024 Scientific Chair. ESMO Previous Highlights: Neo-Adjuvant Therapy for Triple Negative Breast Cancer, Checkpoint Inhibition, AI, Cancer Vaccines, and More ……” BARCELONA, Spain—At the last Annual Meeting of the European Society for Medical Oncology (ESMO), medical oncologist Rebecca Dent MD, Deputy Chief Executive Officer at the National Cancer Centre in Singapore, told Peter Goodwin what had, for her, been the key areas of progress in cancer medicine announced at the meeting in which significant advances had been made. Audio Journal of Oncology with Rebecca Dent MD IN: [Goodwin] “With the 2025 meeting of ESMO about to happen …. OUT: ….in Singapore. Thanks very much. 13:13 secs https://www.esmo.org/meeting-calendar/esmo-congress-2024/programme MORE: Professor Rebecca Dent MD MSc is a career-long clinical and translational researcher as well as education-focused, academic clinician with sub-specialist interest in all aspects of triple negative breast cancer (TNBC) and young women with breast cancer. Prof. Dent achieved her MD from McMaster University in Hamilton, Ontario, Canada and then completed her internal medicine and medical oncology residency at the Princess Margaret Hospital and the Sunnybrook Odette Cancer Center in Toronto, Canada. This was followed by a fellowship in breast cancer, supported by a Marion Walker Women’s Health Scholarship, and MSc in Clinical Epidemiology and Statistics at the University of Toronto. During her training Prof Dent was fortunate to have completed electives across Canada, the US (Memorial Sloan Kettering), France (Institut Marie Curie) and the Philippines (Philippine General Hospital). In her North American academic career, Prof Dent served as Chair of the locally advanced breast cancer program and Head, Breast Cancer Clinical Trials Unit at the Sunnybrook Odette Cancer Center from 2008-2011. Her seminal publication whilst in Toronto was a Clinical Cancer Research publication, one of the first to describe what is now known as triple negative with almost 5,500 citations for this individual paper (Dent R et al. Clin Ca Res 2007). She was the PI of one of the first Phase I PARP inhibitor trials in unselected TNBC in combination with taxane chemotherapy and she served as a reviewer for the National Cancer Institute of Canada (NCIC) grants committee. As a consultant at the Sunnybrook Odette Cancer Center, she supervised a number of residents and fellows and was awarded an Outstanding Teaching Award by the University of Toronto. Prof Dent has participated in the ASCO Leadership Development Program and served on a number of ASCO Committees: Education including Chair, Breast Track and Member of the Breast Scientific Committee (ER/HER2 track), as well as on the Editorial Board of the Journal of Clinical Oncology (JCO). In February 2011, Prof Dent moved to Singapore where she is now senior consultant at the National Cancer Center in Singapore (NCCS). Recognizing the need for pan-Asian regional educational interaction Prof Dent co-founded and co-chaired nine Asia Pacific Breast Cancer Summits (https://apbcs.org). Consequently Prof Dent was involved in the establishment of the ESMO Asia meeting subsequently serving as Scientific Chair and Co-Chair Breast Track. Prof Dent has co-chaired the ESMO Breast Preceptorship in Singapore since 2017 and sits on the pan-Asian ESMO adapted guidelines committee as well as the Advanced Breast Cancer ESMO guideline committee. Prof Dent serves as a scientific committee member of the ASCO Breakthrough Asia Meeting. Prof Dent is currently Chair of the ESMO Nomination Committee and a member of the ESMO Council. Prof Rebecca Dent has over 18,000 citations and an h-index over 50. She sits on the Editorial Board of The Lancet Oncology. She has been invited as an oral and plenary discussant at ESMO as well as an invited speaker at numerous meetings for ASCO, ESMO Asia, and other meetings across Asia such as the Japanese Society of Medical Oncology and Korean Society of Medical Oncology. Prof Dent is a steering committee member and PI for a number of large international trials evaluating novel agents in the treatment of TNBC. Funding was secured for a novel investigator initiated global study evaluating the role of PARP inhibition with or without immune checkpoint inhibition in platinum sensitive TNBC which has just completed recruitment in the US, Korea and in Singapore (The DORA study). This is a pivotal Duke NUS Singapore and Duke USA collaboration. As of October 2018, Prof Dent has been Head of the department of Medical Oncology at the National Cancer Center Singapore (NCCS) at SingHealth. NCCS has recently been designated as a comprehensive cancer center and Prof Dent was appointed Chairman of the Division of Medical Oncology in 2021. Prof Dent maintains a busy clinical practice, as well as teaching medical students at Duke-NUS. This has been r

Audio Journal of Oncology interview with: Bart Neyns MD PhD, Vrije Universiteit Brussel, Faculty of Medicine and Pharmacy, Medical Oncology Department, Brussels, Belgium BARCELONA, Spain—Intracranial administration of autologous dendritic cells was combined with combination checkpoint inhibition in a phase 1 study of patients with recurrent glioblastoma that reported marked clinical responses to the European Society for Medical Oncology (ESMO) annual meeting in Barcelona. Cells harvested from each patient were injected directly into the brain tissue resection cavity lining after surgery. Patients also received intra-cranial injections of the checkpoint inhibitor combination: nivolumab plus ipilimumab. At the conference, Peter Goodwin discussed the research with lead author of the study, Bart Neyns MD PhD, Head of Medical Oncology at the Vrije Universiteit, Brussel, in the University Hospital Brussels Faculty of Medicine & Pharmacy, Brussels, Belgium. Audio Journal of Oncology interview with: Bart Neyns MD PhD, Vrije Universiteit Brussel, Faculty of Medicine and Pharmacy, Medical Oncology Department, Brussels, Belgium IN : “Patients with recurrent glioblastoma …. OUT:…from me, Peter Goodwin, goodbye 10:54 secs SOURCE: ESMO 2024 Barcelona ESMO Abstract 441O Neyns , Medical Oncology Department, Vrije Universiteit Brussel – Faculty of Medicine & Pharmacy, Brussels, Belgium “A phase I clinical trial on the intracranial administration of autologous CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid dendritic cells (myDC) in combination with ipilimumab (IPI) and nivolumab (NIVO) in patients with recurrent high-grade glioma (rHGG)” Reference: CNS tumours Volume 35, Supplement 2S406-S407 September 2024Authors: Neyns1 ∙ I. Dirven1 ∙ L. Lescrauwaet2 ∙ M. Cammaert1 ∙ W. Geens2 ∙ X. Geeraerts1 ∙ L. Stevens1 ∙ S. Brock3 ∙ M. Kockx4 ∙ H. Everaert5 ∙ A-M. Van Binst6 ∙ S. Tuyaerts1 ∙ J. Duerinck7 1. Medical Oncology Department, Vrije Universiteit Brussel – Faculty of Medicine & Pharmacy, Brussels, Belgium 2. Neurosurgery, UZ Brussel – Universitair Ziekenhuis Brussel, Jette, Belgium 3. Pathology, UZ Brussel – Universitair Ziekenhuis Brussel, Jette, Belgium 4. Pathology Department, CellCarta, Antwerpen, Belgium 5. Nuclear Medicine, Vrije Universiteit Brussel – Faculty of Medicine & Pharmacy, Brussels, Belgium 6. Radiology Department, Vrije Universiteit Brussel – Faculty of Medicine & Pharmacy, Brussels, Belgium 7. Neurosurgery Department, Vrije Universiteit Brussel – Faculty of Medicine & Pharmacy, Brussels, Belgium https://www.audiomedica.com/wp-content/2025/09/241011-Bart-Neyns-ESMO-AJO-PRODUCTION-MASTER.mp3Background Intracranial admin of NIVO and IPI following the resection of rHGG is safe and has resulted in encouraging survival (J Duerinck et al. JITC 2021). myDC play a pivotal role in initiating an adaptive anti-tumor immune response and licensing of immune anti-tumor effector cells within the tumor microenvironment. Methods rHGG pts (after prior RT and TMZ, <8 mg methylprednisolone QD), underwent a leukapheresis followed by isolation/cryopreservation of myDC. NIVO (10 mg IV) was administered preoperatively. myDC (5-, 10-, or 20.106 cells) were injected into the brain tissue lining the resection cavity (iCer) following a maximal safe resection (MSR) or intratumorally (iTum) following a stereotactic biopsy (STX). IPI (5 mg) plus NIVO (10 mg) were co-injected iCer or iTum with the myDC. Postoperative NIVO was administered intracavitary (iCav, 10 mg) and intravenously (IV, 10 mg) Q2w (max 11x). Results 21 pts (13 M; med 49 y [range 20 -78]; IDHwt 17 pts, ECOG PS 0 or 1: 18-, 3 pts) underwent procurement of myDC; intraoperative administration of myDC was preceded by MSR in 19 pts, and STx in 2 pts. Respectively 6, 3, and 12 pts were treated at the 3 myDC dose levels. All pts received the peri-op iTum/iCer/IV-admin of IPI and NIVO as planned. The median postop iCav and IV NIVO-admin was 7 (range 0-11) and 8 (0-11). Study treatment was discontinued early for PD in 9- and AE in 3 pts. Most important TRAEs: bacterial colonization of the Ommaya reservoir (n=4), craniotomy wound dehiscence (n=2), and bacterial meningitis (n=1). At DBL (01MAY2024), 6 pts (29%) remain progression-free (incl. 3 pts with >2y PFS). PFS (med. 24w [95% CI 8- 39]) is superior when compared to the pts (n=70) with resectable rHGG treated in 4 other cohorts of the GlITIpNi trial (p=0.003). When including the durable benefit from bevacizumab at first PD in 3 pts, PFS compared favorably to a historical pooled cohort (n=469) of rHGG treated with VEGF(R)-inhibitors (p=0.007). The 1-year OS-rate was 50% [95% CI 24-76]. Conclusions Intracranial administration of myDC combined with IPI/NIVO is feasible, safe and associated with encouraging survival, deserving further investigation.