Citations

Mayo Clinic

Showing 10 of 108453 citations.

Treatment-related toxicities of antibody-drug conjugates in breast cancer: A Bayesian network meta-analysis.
Yiqun Han, Yuan Yao, Yucai Wang, Yoshito Nishimura, Yi Lin, Meng Xu Welliver, Kathryn Jean Ruddy, Robert Mutter

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e15015 Get It

e15015 Background: Antibody-drug conjugates (ADCs) have demonstrated significant efficacy in treating patients with breast cancer. However, the toxicity variations between these agents are not yet thoroughly elucidated. This study aims to systematically compare the toxicity profiles of various ADCs used in breast cancer therapy to better inform clinical decision-making. Methods: We conducted a systematic review of randomized controlled trials (RCTs) published by September 2024. Treatment-related adverse events (TRAEs) of the investigational ADCs and standard of care control were classified into systemic categories based on Common Terminology Criteria for Adverse Events. Bayesian models were employed to facilitate the indirect comparisons of TRAEs associated with different ADCs and reported using surface under the cumulative ranking curve (SUCRA) values. The study protocol was prospectively registered on PROSPERO (CRD42024606194). Results: A total of 9307 patients in 17 RCTs of five different ADCs (ado-trastuzumab emtansine [T-DM1], sacituzumab govitecan [SG], trastuzumab deruxtecan [T-DXd], datopotamab deruxtecan [Dato-DXd], and ARX788) were included. SG and T-DXd monotherapy were associated with the highest risk of neutropenia/anemia, with SUCRA values of 11.2%/26.7%, and 20.7%/17.1%, respectively. T-DM1-containing regimens had the highest incidence of thrombocytopenia, which was exacerbated when combined with chemotherapy compared to monotherapy. In terms of gastrointestinal (GI) toxicities, SG was associated with the highest risk of diarrhea, followed by comparable risks between T-DM1 combined with chemotherapy and anti-HER2 and chemotherapy combined with dual anti-HER2 therapy. T-DXd was associated with a relatively higher incidence of vomiting (9.5%), while the highest risk of nausea was seen with chemotherapy with dual anti-HER2 therapy and T-DXd. SG and T-DXd were more likely to cause fatigue, decreased appetite, and dermatological disorders, including alopecia, rash, and pruritus, while T-DM1 combined with anti-HER2 therapies was linked a higher risk of pyrexia. T-DM1-containing regimens were also related to liver function test abnormalities, musculoskeletal and neurological disorders. Dato-DXd was associated with a higher risk of fatigue and dermatological toxicities, while ARX788 was associated with the least hematological and GI TRAEs. Conclusions: This Bayesian network meta-analysis highlights significant variability in TRAEs among different ADCs in breast cancer therapy. T-DM1 was primarily associated with thrombocytopenia and hepatic toxicities, while SG and T-DXd were associated with neutropenia, anemia, GI disorders, and dermatological TRAEs. Our findings may help with selection of ADC therapies for patients with breast cancer, facilitating personalized approaches to minimize treatment-related toxicities.
Comparisons of survival outcomes of antibody-drug-conjugates in metastatic breast cancer: A network meta-analysis.
Welliver, M.X., Ruddy, Kathryn J. , Mutter, Robert W. , Han, Yiqun , Yao, Yuan , Wang, Yucai , Nishimura, Yoshito , Lin, Yi

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e15003 Get It

e15003 Background: Antibody-drug conjugates (ADCs) have shown substantial promise as therapies for metastatic breast cancer (mBC). However, direct comparisons of different ADC-based regimens are limited. We assessed survival outcomes in mBC patients treated with ADCs. Methods: Randomized controlled trials (RCTs) published before October 2024 were searched in Medline, Embase, ClinicalTrials.gov, and Cochrane Library. Progression-free survival (PFS) and overall surcvival (OS) outcomes were extracted from the most updated publications. Participants were stratified based on molecular subtypes, hormone receptor (HR) status, duration of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) treatment, and sensitivity to endocrine therapy (ET). Bayesian frameworks were deployed, presenting the synthesized outcomes of indirect comparisons using the surface under the cumulative ranking curve (SUCRA), hazard ratio (HR), and 95% credible interval (Crl). This study was prospectively registered on the International Platform of Registered Systemic Reviews and Meta-analysis Protocols (INPLASY) (INPLASY2024110021). Results: A total of 6449 patients from 12 RCTs of ADCs ado-trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd), and datopotamab deruxtecan (Dato-DXd) were included in the analysis. Compared to chemotherapy, T-DXd significantly improved PFS (HR 0.35, 95% Crl 0.15-0.84) and OS (HR 0.56, 95% Crl 0.32-1.0). SG also significantly extended OS (HR 0.65, 95% Crl 0.43-0.97) but not PFS. In HER2+ mBC, pooled analyses revealed T-DXd was the most effective treatment in terms of PFS, with a SUCRA of 94.2%, followed by T-DM1 (58.9%), and chemotherapy with HER2-directed therapy (34.2%). Synthesized outcomes of OS mirrored the PFS outcomes. In HR+/HER2- mBC (some of which was HER2-low), Dato-DXd (76.1%) showed slightly superior efficacy over SG (67.4%) for PFS, while SG (85.1%) was advantageous over Dato-DXd (49.1%) in terms of OS. Among patients with HR+/HER2+ mBC, T-DXd (80.0%), SG (55.5%), and chemotherapy with HER2-directed therapy (53.1%) were the most effective therapies for prolonging PFS. Regarding OS, SG (70.3%) and T-DM1 (60.3%) were the most effective, with comparable efficacy observed between chemotherapy with HER2-directed therapy (52.1%) and T-DXd (52.0%). In HR-/HER2+ mBC, T-DXd (78.1%), SG (56.1%), and T-DM1 (51.5%) significantly prolonged PFS, while SG (69.4%) had the most substantial benefit for OS, followed by T-DXd (62.8%) and chemotherapy with HER2-directed therapy (57.6%). Dato-DXd showed an advantage over SG in mBC patients received CDK4/6i for > 12 months. Conclusions: This network meta-analysis showed prominent survival benefits with ADC-containing regimens for mBC. Our results provide valuable insights into personalized treatment strategies for mBC patients.
Safety and efficacy analysis of modified TOPAZ-1: A biweekly regimen of gemcitabine and cisplatin plus monthly durvalumab in advanced biliary tract cancer.
Kamatham, Saivaishnavi , Abdel-Razeq, Nayef Hikmat, Elalfy, Aya, Chiriboga, Guido , Fonkoua, Lionel Aurelien Kankeu , Wu, Christina, Starr, Jason S. , Ahn, Daniel H. , O’Donnell, Conor, Mosalem, Osama , Abdelhakeem, Ahmed , Jones, Jeremy C , Conboy, Caitlin B. , Sonbol, Mohamad Bassam , Babiker, Hani M. , Bekaii‐Saab, Tanios , Tran, Nguyen H. , Borad, Mitesh J. , Majeed, Umair

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e16265 Get It

e16265 Background: The pivotal TOPAZ-1 trial established durvalumab plus gemcitabine and cisplatin (GC) as a new first-line standard of care for advanced biliary tract cancer (ABTC). However, weekly administration of GC can lead to significant toxicity limiting its tolerability in clinical practice. Based on previous studies, we implemented biweekly regimen of GC on days 1 and 15 together with durvalumab on day 1 of each 28-day cycle to optimize the treatment delivery and improve tolerability. Here, we report the Mayo Clinic experience with biweekly GC with monthly durvalumab in patients with ABTC. Methods: At our three-site institution, we retrospectively identified patients with ABTC between January 2021 and August 2024, who received biweekly GC with monthly durvalumab. Patient demographics, tumor characteristics, treatment details - treatment related adverse events (trAEs) graded according to the NCTCAE V5.0 were collected. Outcomes included median progression-free survival (mPFS), median overall survival (mOS) and clinically assessed overall response rate (ORR) and disease control rate (DCR). Results: 57 patients were included in our analysis, median age was 68 years (range 35-90), and 57.9% were females. 91.2% of patients had ECOG performance status of 0-1. 71.9% had intrahepatic cholangiocarcinoma, 19.3% extrahepatic cholangiocarcinoma and 8.7% gallbladder carcinoma. 70.2% had metastatic disease, 21 % locally advanced unresectable disease and 8.7% recurrent metastatic disease. Patients were followed for a median of 9.1 months (2.3-28.5). 91.2% of the patients received biweekly GC plus monthly durvalumab while 8.8% switched from weekly to biweekly GC plus monthly durvalumab due to treatment toxicities. Median number of treatment cycles was 5. Maintenance regimens included durvalumab (19.3%), gemcitabine/durvalumab (8.8%) and GC/durvalumab (8.8%). Median duration of follow up was 9.1 months (range 2.3 – 28.5). ORR was 36.9% and DCR was 72% (complete response 5.3%, partial response 31.6% and stable disease 35.1%). mPFS was 7.2 months, while mOS was 16 months. Grade(G) 3 or 4 trAEs included abnormal liver function tests (15.7%), infections (11.5%), anemia (8.7%), thrombocytopenia (5.2%), peripheral neuropathy (1.7%), acute kidney injury (1.7%). Immune-related AEs were noted in 6 patients (10.5%) including colitis, gastritis, hepatitis, myocarditis and hypothyroidism. There was no patient with severe neutropenia or febrile neutropenia. Only 5 patients (8.8%) stopped treatment due to trAEs. Conclusions: Biweekly GC on days 1 and 15 plus durvalumab on day 1 of each 28-day cycle is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in the TOPAZ-1 trial indicating that a de-escalation strategy is feasible with improvement in patient centered outcomes.
Dissecting publication timelines: Insights from high-impact oncology journals.
Aljafari, Abdulmalek , Khairi, Ahmad, Aljafari, Abdulmoiz , Hebishy, Ahmed, Batoo, Sameer, Mohammad, Abdulkader

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 9037-9037

10.1200/jco.2025.43.16_suppl.9037 Get It

9037 Background: Efficient dissemination of research findings is critical in oncology, where timely access to new knowledge impacts clinical care and outcomes. This study analyzes publication timelines of high-impact oncology journals to identify patterns and determinants, including research categories and study designs. Methods: This is a retrospective observational study. Journals with the highest impact factors and available publication timeline data were included: Journal of Clinical Oncology, Molecular Cancer, Clinical Cancer Research, and Cancer Discovery. All articles published in 2023 were analyzed for submission-to-acceptance, acceptance-to-publication, and total publication times. Data were processed using SPSS, and statistical comparisons were made with the Kruskal-Wallis test (significance: p<0.05). Results: A total of 875 articles were analyzed. The overall median total publication time (TT) was 7.1 months (IQR: 5.7–8.9), with submission-to-acceptance (AT) and acceptance-to-publication (PT) medians of 4.8 months (IQR: 3.5–6.3) and 2.2 months (IQR: 1.6–2.6), respectively. Among journals, Molecular Cancer exhibited the shortest TT (median: 4.7 months; IQR: 3.1–6.6), while Cancer Discovery had the longest TT (median: 8.8 months; IQR: 6.8–10.6). Similarly, Molecular Cancer achieved the fastest AT (median: 3.9 months; IQR: 2.2–5.4) and PT (median: 0.6 months; IQR: 0.4–1.1). Conversely, Cancer Discovery recorded the slowest AT (median: 6.0 months; IQR: 4.5–7.8) and PT (median: 2.8 months; IQR: 2.4–3.2). In terms of research categories, blood cancer articles accounted for the largest proportion of publications (14.4%), followed by gastrointestinal cancer (13.9%). Articles in genitourinary (median TT: 6.4 months; IQR: 5.5–8.8) and cardiac cancer (median TT: 6.5 months; IQR: 5.9–6.9) categories had the shortest TT, while endocrine (median TT: 7.9 months; IQR: 5.6–10.9) and immunotherapy (median TT: 9.1 months; IQR: 6.8–10.5) categories exhibited the longest TT (p<0.05). Clinical trials were the most common study design (37.6%), followed by cross-sectional studies (19.5%). Systematic reviews had the shortest TT (median: 2.4 months; IQR: 1.9–9.2), while proof-of-concept studies required the longest TT (median: 9.5 months; IQR: 8.7–10.7) (p<0.05). Systematic reviews and database studies also had the shortest PT (median: 1.5 months), whereas proof-of-concept studies had the longest PT (median: 2.8 months; p<0.001). Conclusions: Publication timelines in oncology journals vary significantly by journal, research category, and study design. Molecular Cancer demonstrates the fastest publication processes, while Cancer Discovery exhibits the slowest. Genitourinary and dermatologic oncology categories, as well as systematic reviews, achieve the most expedited timelines, emphasizing the need to consider category and study design in publication planning.
Applying learning science principles (LSP) through a simulation session (SIM) for oncology trainees (OT) about fertility preservation (FP) in patients (pts) with cancer and treatment (tx) of pregnant pts (TPP) with cancer.
Pai, Tanmayi , Correia, Guilherme Sacchi de Camargo, Wysokinska, Ewa , Abdel-Razeq, Nayef Hikmat, Adeoye, Oluwatayo , Aldapt, Mahmood B, Kamatham, Saivaishnavi , Tawfiq, Reema, Wolf, Emily, Rao, Rohit , Tan, Winston, Ventro, Sandra, Abdelhakeem, Ahmed , Baidoun, Firas , Elantably, Dina , Gupta, Kush , Mosalem, Osama , Wiest, Nathaniel E. , Iqbal, Madiha , Tan, Winston, Manochakian, Rami

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 9029-9029

10.1200/jco.2025.43.16_suppl.9029 Get It

9029 Background: Addressing guideline concordant FP and TPP with cancer is challenging, especially for OT. SIM, a well-known education tool, has not been traditionally used to teach these topics. As part of the hematology/oncology fellowship curriculum, we designed a SIM applying LSP to bridge this educational gap. Methods: Applying LSP of contrasting cases, elaboration, feedback, generation and just-in-time telling, chief OTs and faculty designed a SIM with 3 clinical scenarios (CS) and 3 standardized pts (SP): FP for a female pt hospitalized for acute lymphoblastic leukemia tx, FP for a male pt in clinic for germ cell tumor tx, and breast cancer tx for a pregnant pt in 2 nd trimester. OT received written educational materials (WEM) and attended a lecture 1 week and 1 day pre SIM, respectively. OT were split into 2 groups; 1 started in the FP CS and 1 in the TPP CS, and then they switched. To reduce cognitive overload, each OT participated in 1 of 2 FP CS: half in the female FP CS and half in the male. Faculty and chiefs led debriefing sessions after all CS. The FP debrief ended with a special “learner as a teacher” part, where OT who attended the female CS taught those from the male CS about their topic and vice versa. The SIM concluded with "take-home" points. Pre (after having WEM) and post SIM anonymous surveys and verbal feedback assessed OT comfort, perceptions, and knowledge. Results: A 3 hour SIM with 14 OT and 5 faculty was completed successfully. SIM ended with all OT verbally sharing a learning point and positive feedback. All OT filled pre and post SIM surveys. Pre SIM, 17% reported having prior FP education, and 42% had prior TPP education. However, only 8% and 25% felt adequately prepared for FP and TPP discussions, respectively. Post SIM survey showed major improvement in comfort and knowledge about FP and TPP (see table 1). 75% of OT favored a combination of SIM and learning by teaching over other SIM formats. 83% supported having a TPP lecture before SIM. 100% reported satisfaction with FP and TPP SIM’s quality and wanted similar activities in the future. 92% were satisfied with the learner as a teacher tool. 100% felt education about FP and TPP with cancer should be part of fellowship training. Moral/cultural concerns were discussed as possible challenges in FP education. Conclusions: The application of LSP through SIM significantly increased OTs’ comfort discussing FP and TPP with cancer, and objectively enhanced their knowledge on these topics compared to after reading WEM. The SIM was largely perceived as a successful activity to educate about challenging topics and should become part of fellowship curriculum. Pre SIM % Post SIM % Comfortable addressing FP 17 92 Comfortable addressing TPP 8 100 Correct answers about female FP 63 83 Correct answers about male FP 67 94 Correct answers about TPP with cancer 68 98
Assessment of tumors, blood, and ascites to establish correlations with treatment benefit in platinum resistant or refractory ovarian cancer patients treated with igrelimogene litadenorepvec and pembrolizumab combination therapy.
Cervera, Victor, Block, Matthew S. , Mäenpää, Johanna , Arias, Victor , Heijden, Mirte van der , Haybout, Lyna , Ramadan, Susan, Sorsa, Suvi , Santos, João M. , Clubb, James H.A. , Pakola, Santeri A. , Quixabeira, Dafne C.A. , Kudling, Tatiana Viktorovna , Jirovec, Elise , Alanko, Tuomo , Adamo, Daniel A. , Sormunen, Jorma , Chisamore, Michael Jon , Hemminki, Akseli

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 5555-5555

10.1200/jco.2025.43.16_suppl.5555 Get It

5555 Background: Platinum-resistant/refractory ovarian cancer presents a significant therapeutic challenge and despite several attempts, immunotherapies have not delivered satisfactory results to be approved. Identifying biomarkers of response to novel therapies is crucial for personalizing treatments and improving patient outcomes, especially since certain patients do experience long term benefit after the treatment with pembrolizumab and igrelimogene litadenorepvec (TILT-123; an oncolytic adenovirus coding for TNF and IL-2). Methods: Tumor biopsies (n=62), ascites (n=8) and blood (n=234) were collected from 15 patients treated in the PROTA trial (Phase I, NCT05271318). These patients received pembrolizumab intravenously plus igrelimogene litadenorepvec intravenously, followed by local administration intratumorally or intraperitoneally. Sampling took place prior to therapy, during therapy and after it. Tumor proteome (IHC, mIF) and transcriptome was analyzed to assess immune changes and virus presence. Ascites and blood samples were assayed to measure cell counts, phenotypes, cytokine and protein counts, as well as for the presence of antiviral neutralizing antibodies (NAbs). Biological parameters were correlated with overall survival (OS), RECIST 1.1 evaluations and tumor size changes. For analysis of OS, logrank test was used. For group comparisons two-tailed Mann-Whitney U-test was used. Pearson or Spearman tests were used for correlations. Results: Patients experiencing a drop in circulating lymphocytes 8-24 hours after treatment were more likely to experience longer OS (p=0.044). Additionally, patients with a higher lymphocyte count at baseline experienced similar OS benefit (p=0.018) plus a positive correlation with disease control (p=0.023). Most patients (11/15) showed antiviral immunity at baseline but eventually all patients developed neutralizing activity, and the same was observed in ascites. The presence of NAbs at baseline as well as development of highest titers were positively correlated with longer OS (p=0.004) and disease control (p=0.003). Conclusions: Igrelimogene litadenorepvec and pembrolizumab are therapies designed to attract, activate and/or protect lymphocyte-mediated antitumor activity. These findings suggest that having a fit immune system able to mobilize effector immune cells as well as responding to immunostimulant agents increases therapeutic success. As a disease with few therapeutic options, ovarian cancer patients often receive multiple lines of chemotherapy that might decrease the efficacy of immediate immunotherapies. The potential use of these biomarkers will be studied in larger studies to validate their utility in guiding the use of immunotherapy in this challenging patient population. Clinical trial information: NCT05271318 .
A phase II trial of pembrolizumab and lenvatinib in recurrent or persistent clear cell ovarian carcinoma (NCT05296512).
Lee, Elizabeth Katherine, Hendrickson, Andrea E. Wahner , Krasner, Carolyn, Stover, Elizabeth H. , Porter, Rebecca L. , Matulonis, Ursula A. , Xiong, Niya , Sawyer, Hannah, Tayob, Nabihah , Lee, Elizabeth Katherine , Zhou, Yinglu , Fleming, Gini F. , Konstantinopoulos, Panagiotis A. , Horowitz, Neil S. , Wright, Alexi A. , Sawyer, Hannah , Liu, Joyce F.

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 5515-5515

10.1200/jco.2025.43.16_suppl.5515 Get It

5515 Background: Clear cell ovarian carcinoma (CCOC) is a chemoresistant subtype of ovarian cancer. Immune checkpoint inhibitors have been reported to have clinical activity in CCOC. Additionally, CCOC harbors molecular alterations suggesting a role for anti-angiogenic agents. We therefore conducted a single-arm two-stage phase 2 trial to investigate the clinical activity of the combination of the PD-1 inhibitor pembrolizumab with the anti-angiogenic tyrosine kinase inhibitor lenvatinib in patients (pts) with CCOC. Methods: Pts with CCOC and measurable disease received pembrolizumab 200 mg IV every 3 weeks and lenvatinib 20 mg daily. Pts could have received an unlimited number of prior therapies; prior bevacizumab and immune checkpoint inhibitors were allowed, but prior lenvatinib was exclusionary. Malignant bowel involvement was not allowed. Co-primary endpoints were objective response rate (H 0 5%; H a 25%) and rate of PFS at 6 months (mo) per RECIST v1.1 (H 0 10%; H a 30%), restricting the probabilities of type I and type II errors to 10% and 10%, respectively. Two pts with objective responses or 3 pts progression-free and alive at 6 mos were needed to proceed from stage 1 (n=18) to stage 2 (n=13); 5 pts with objective responses or 6 pts progression-free and alive at 6 mos were needed to declare the combination worthy of further study. Results: Data cut-off occurred 22-Oct-2024. Of 30 enrolled pts, 83.3% were white; the mean age among all pts was 54.1 years. 30% of pts (9/30) experienced a confirmed response (2 CR, 7 PR); an additional 3 pts (10%) experienced unconfirmed PRs and 4 pts (13.3%) had SD ≥6 mo. As of data cut-off, 3 pts (10%) had not yet reached their first radiographic assessments, and 17 pts were still receiving study therapy. With a median of 9.72 mo of follow up, 16 pts were alive and progression-free at 6 months. The estimated 6-month PFS was 75.96% (95% CI 53.82-88.51%). Median PFS was 10.9 mo. The estimated 12-month PFS was 48.86% (95% CI 23.67-70.04%). The most common any-grade TRAEs were hypertension (71%), hypothyroidism (66%), and fatigue (60%). There were no unanticipated TRAEs. Conclusions: The combination of pembrolizumab/lenvatinib demonstrates encouraging evidence of clinical activity in CCOC, with 9 pts experiencing a confirmed response and 16 pts alive and progression-free at 6 months. As both co-primary endpoints of the study were met, enrollment closed with 30 pts. Updated data for all pts will be reported. There were no new safety signals. Clinical trial information: NCT05296512 .
Interim safety and efficacy data of [ 212 Pb]VMT01 in MC1R expressing melanoma.
Block, Matthew S. , Mehr, Samuel H., Baratto, Lucia , Tomash, Haley, Yang, Wenjing , Puhlmann, Markus , Morris, Zachary Scott , Wahl, Richard L. , Marsh, Ian R. , O’Keefe, Stephen J. , Menda, Yusuf

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 3099-3099

10.1200/jco.2025.43.16_suppl.3099 Get It

3099 Background: Immune checkpoint inhibitors (ICI) are effective in melanoma, but many patients experience progression on or after approved ICI +/- MAPK inhibitor therapy. Melanocortin-1 receptor (MC1R) is a novel target for radiopharmaceutical therapy (RPT) and is highly expressed on melanoma tumor cells. VMT01 is an MC1R-targeted RPT that can be radiolabeled with either 203 Pb (patient selection and dosimetry assessments) or 212 Pb (alpha particle therapy). Here, we present data on the first in-human evaluation of [ 203 Pb/ 212 Pb]VMT01 in patients with metastatic melanoma. FDA granted Fast Track Designation to the product on the bases of preclinical experiments combining [ 212 Pb]VMT01 with immunotherapy. Methods: This is a first-in-human dose-finding study to determine the safety, pharmacokinetics, dosimetry and preliminary efficacy of [ 212 Pb]VMT01 in subjects with MC1R-positive metastatic melanoma who progressed on at least 1 approved first-line therapy (NCT05655312). Phase 1 of the trial includes escalating dose cohorts. The first two cohorts incorporate dosimetry evaluations (reported separately) with the imaging surrogate [ 203 Pb]VMT01 prior to receiving up to 3 treatment cycles of [ 212 Pb]VMT01 therapy (injected activity of 111 MBq (3 mCi) or 185 MBq (5 mCi) for Cohort 1 and 2, respectively). Participants are evaluated for any DLT for the first 6 weeks after cycle one. Efficacy is assessed by RECIST 1.1 criteria by the investigator. Following the start of the study the anticipated combination arm with nivolumab was opened as an amendment. Results: Cohort 1 (DCO 04Sep24) was completed with 3 enrolled participants who received 3 treatment cycles without any DLTs or SAEs. Cohort 1 participants showed prolonged stabilization of disease from start of treatment (mean: 11.1 months); one participant developed a confirmed objective response (PR) after completion of all three [ 212 Pb]VMT01 administrations and is still on trial after 13.1 months from start of treatment. Cohort 2 has completed with 7 enrolled participants. No DLTs or related SAEs have been observed. All participants in this Cohort progressed after either the first cycle (3 participants) or the second cycle (4 participants).Based on these preliminary results showing anti-tumor effect at the lower dose, additional cohorts for both monotherapy and in combination with nivolumab were introduced at a de-escalated dose of 55.5 MBq (1.5 mCi). Both cohorts are now open for enrollment. Updated safety and efficacy data will be analyzed and presented at ASCO. Conclusions: At 111 MBq and 185 MBq activity levels, [ 212 Pb]VMT01 was safe and well-tolerated. An objective response and prolonged stabilization of disease were observed at the 111 MBq activity level while no effect was seen at 185 MBq. The study will continue to explore potentially immunostimulating lower doses of administered activity of [ 212 Pb]VMT01 either as a monotherapy or in combination with nivolumab. Clinical trial information: NCT05655312 .
Phase 2 multicenter clinical trial to evaluate the safety and efficacy of abenacianine for injection (VGT-309), a tumor-targeted, intraoperative molecular imaging agent, for patients undergoing surgery for cancer in the lung.
Singhal, Sunil, Kim, Jae Y. , Reisenauer, Janani , Rice, David C. , Singhal, Sunil Kumar , Herrera, Luis J., Wright, Gavin Michael

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 3069-3069

10.1200/jco.2025.43.16_suppl.3069 Get It

3069 Background: Molecular targeted agents have revolutionized cancer diagnosis and treatment. Intraoperative molecular imaging (IMI) is a novel technique that entails performing real-time, in vivo optical imaging during surgery to ensure cancer clearance. A multicenter clinical trial was conducted using abenacianine, a cathepsin targeted near-infrared (NIR) IMI agent to visualize pulmonary nodules during surgery. The primary objective was to assess the efficacy of abenacianine in localizing pulmonary lesions, evaluating surgical margin, and identifying unsuspected disease. Methods: Participants scheduled to undergo surgery for known or suspected cancer in the lung received abenacianine (0.32 mg/kg intravenous) preoperatively 12 to 36 hours before surgery. During a standard-of-care surgery, the lung underwent IMI and additional disease not identified by conventional methods were identified and analyzed. Efficacy was measured by frequency of clinically significant events (CSEs) defined as localization of lesions not found by standard surgical techniques, identification of additional cancers, identification of positive surgical margins confirmed by histology, and detection of cancerous lymph nodes. Results: 89 participants were included in the study. The mean age was 67 years and 57 (64%) were female. Of 89 participants administered abenacianine who underwent standard of care surgical resection for known or suspected cancer in the lung, 40 (45%) had at least one CSE. Abenacianine with NIR imaging identified lesions that were not found by standard surgical methods in 34 (38%) participants, synchronous and occult cancers that were not found by pre-operative imaging in 2 (2%), margins within 10 mm of the closest staple line in 8 (9%), and lymph nodes determined to be cancerous in 1 (1%) participant. Tumors visualized by IMI with abenacianine included non-small cell lung cancers (adenocarcinoma, squamous cell carcinoma, neuroendocrine tumor) and cancers that metastasized to the lung (breast, colorectal, prostate, thymoma, renal cell, sarcoma). Abenacianine was safe and well tolerated in this study; there were no drug-related serious adverse events. Conclusions: This Phase 2 multicenter study demonstrated that using IMI with abenacianine during standard-of-care lung cancer surgery markedly improved clinical outcomes. Abenacianine localized tumors intraoperatively, identified synchronous and occult lesions, helped assess negative margin status, and identified cancerous lymph nodes enabling a more complete oncologic resection. Clinical trial information: NCT06145048 .
Perceptions of Vietnamese women regarding HPV self-collection: A cross-sectional analysis.
Dinh, Tri, Islam, Nadia, Dinh, Tri

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e17530 Get It

e17530 Background: Cervical cancer remains a significant public health challenge, especially in low-resource settings such as Vietnam. HPV self-collection offers a promising avenue for improving screening uptake, yet its acceptance depends on addressing knowledge gaps and sociocultural barriers. This study aims to explore the perceptions of Vietnamese women in regard to HPV and HPV self-collection, emphasizing strategies for health promotion and disease prevention. The aims of this study were to summarize responses to a 51-item survey regarding perceptions of HPV self-collection in Vietnamese women between 30 and 65 years old, as well as to compare survey responses according to age, religion, education level, marital status, and frequency of doctor visits in the past year. Methods: A survey of 538 women aged 30–65 assessed cervical cancer knowledge, attitudes toward HPV self-collection, cost concerns, and communication preferences. Associations between demographic factors and perceptions were analyzed using Wilcoxon rank sum, Kruskal-Wallis, and Fisher’s exact tests (p < 0.05). Results: While 84.4% of respondents were aware of cervical cancer, only 59.0% had knowledge of HPV, and 41.3% were familiar with self-collection. Most women (82.5%) recognized the importance of cervical cancer prevention; however, only 45.5% viewed self-collection as equally effective as doctor-administered testing. For negative self-collection recorded results, 64.3% felt reassured, yet 81.1% preferred secondary confirmation by a doctor (p<0.01). Cost concerns were notable, with 56.5% willing to pay 400,000 VND but fewer accepting higher costs. Education significantly influenced responses, with higher-educated women demonstrating greater awareness and confidence in self-collection (p < 0.001) . Importantly, participants identified doctors and healthcare professionals as trusted sources of information, when compared to other sources of information such as television and government officials, underscoring the role of health promotion campaigns. Conclusions: Effective health promotion strategies are critical to increasing HPV self-collection uptake in Vietnam. Public health campaigns should prioritize education to address misconceptions, emphasize the efficacy of self-collection, and reduce stigma. Programs that leverage trusted communication channels, such as healthcare providers, can foster trust and improve participation. Efforts to ensure affordability and accessibility are essential to achieving equitable and widespread cervical cancer prevention.