tbuckley/cabot-search huggingface dataset:
Abstract CT163: Double lung transplantation in patients with metastatic lung-limited non-small cell lung carcinoma (NSCLC): A case series
Authors: Young Kwang Chae, Chitaru Kurihara, Tarik Demir, Liam Il-Young Chung, Wongi Woo, Carolyn Moloney, Brooke Sanson, Rose Dwyer, Chan Mi Jung, Rade Tomic, Ankit Bharat
Journal: Cancer Research (2025)

Abstract Background: The role of double lung transplantation (DLT) in patients with advanced bilateral lung-limited non-small cell lung cancer (NSCLC) has been a subject of debate. We present a prospective study involving patients who underwent DLT for this indication. Methods: Patients treated with DLT for advanced bilateral lung-limited NSCLC were identified between September 2021 and December 2024 at Northwestern Memorial Hospital. All patients were enrolled in the DLT registry for lung-limited malignancies (DREAM) study cohort A (NCT05671887). Exclusion criteria included the presence of extrapulmonary disease. The indication for DLT was cancer refractory to available systemic treatments, with or without respiratory failure. Results: Eleven patients with advanced bilateral lung-limited NSCLC were included; the median age was 62 years (range 37-71). Two patients (18%) were Asian, eight (73%) were White, one was Black (9%), Six (55%) were female, and three (27%) had a history of smoking. Seven patients (64%) had invasive mucinous adenocarcinoma, and four patients (36%) had invasive non-mucinous adenocarcinoma histology. The median number of pretransplant treatment lines was 3 (range 1-8). All patients experienced disease progression on standard-of-care treatments, with or without participation in clinical trials. The median duration of the waitlist for DLT was 18 days (range 5-414). There was no 30-day mortality. Only one patient experienced a recurrence at 18 months post-DLT, presenting with a 1 cm solid nodule, successfully treated with stereotactic body radiotherapy. Furthermore, the explant pathology revealed malignant cells in the mediastinal and hilar lymph nodes in two patients. With a median follow-up of 16 months (range 1-39), there were no cases of rejection, no patients required oxygen therapy, and all patients remained alive at the time of reporting. Conclusions: Eleven patients with NSCLC underwent DLT successfully without experiencing any significant complications. All patients have survived, with one patient receiving curative treatment after a recurrence, while the remaining patients are currently under observation. Citation Format: Young Kwang Chae, Chitaru Kurihara, Tarik Demir, Liam Il-Young Chung, Wongi Woo, Carolyn Moloney, Brooke Sanson, Rose Dwyer, Chan Mi Jung, Rade Tomic, Ankit Bharat. Double lung transplantation in patients with metastatic lung-limited non-small cell lung carcinoma (NSCLC): A case series [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT163.
Abstract CT108: Beamion LUNG-1 and LUNG-2: The zongertinib clinical program in patients with advanced <i>HER2-</i>mutant non-small cell lung cancer
Authors: Yi-Long Wu, Frans Opdam, Noboru Yamamoto, Tatsuya Yoshida, John Heymach
Journal: Cancer Research (2025)

Abstract Background: There is an unmet need for more effective treatment options for HER2-mutant non-small cell lung cancer (NSCLC), necessitating the development of targeted treatments. Zongertinib is an irreversible tyrosine kinase inhibitor that selectively inhibits HER2 while sparing epidermal growth factor receptor, thereby limiting associated toxicities. The Beamion LUNG-1 phase 1a dose-escalation trial enrolled patients with advanced, unresectable, or metastatic solid tumors with HER2 alterations, refractory to/unsuitable for conventional treatment, or who exhausted treatment options. Preliminary results demonstrate that zongertinib exhibits promising antitumor activity with a manageable safety profile. This abstract describes the subgroups and endpoints of the ongoing Beamion LUNG-1 (phase 1b; NCT04886804) and Beamion LUNG-2 (phase 3; NCT06151574) trials. Methods: Phase 1b of Beamion LUNG-1 is a dose-expansion study evaluating early efficacy of zongertinib in patients with NSCLC with or without prior treatment. Pretreated patients with advanced NSCLC with tumors harboring a HER2 tyrosine kinase domain (TKD) mutation were first enrolled (cohort 1); the study was later expanded to include more cohorts: Treatment-naïve NSCLC with HER2 TKD mutations (2), NSCLC with non-TKD HER2 mutations (3), NSCLC with HER2 TKD mutations and active brain metastases (4), NSCLC with HER2 TKD mutations and prior treatment with platinum-based chemotherapy ± immunotherapy followed by a HER2-directed antibody-drug conjugate (5), and NSCLC with HER2 TKD mutations and prior systemic therapy based in the United States (6, open for enrollment). The primary endpoint is objective response rate (ORR, per RECIST v1.1). Beamion LUNG-2 will evaluate treatment-naïve patients with advanced or metastatic non-squamous NSCLC harboring TKD HER2 mutations, comparing the efficacy/safety of zongertinib with the standard of care (pembrolizumab plus platinum-based chemotherapy [cisplatin/carboplatin and pemetrexed]). The primary endpoint is progression-free survival (RECIST v1.1 assessed by blinded independent centralized review). Key secondary endpoints include overall survival, ORR, duration of response, and patient-reported outcomes. Citation Format: Yi-Long Wu, Frans Opdam, Noboru Yamamoto, Tatsuya Yoshida, John Heymach. Beamion LUNG-1 and LUNG-2: The zongertinib clinical program in patients with advanced HER2-mutant non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT108.
Abstract CT004: KEYLYNK-007: Tumor agnostic trial of olaparib plus pembrolizumab in homologous recombination repair mutation- and homologous recombination deficiency- positive advanced cancers
Authors: Timothy A. Yap, Ronnie Shapira-Frommer, Iwona Lugowska, Tudor Ciuleanu, Miguel Quintela-Fandino, Özgür Özyılkan, Serhii Lysenko, Akira Hirasawa, Simcha Pollack, Rachel Salisbury, Alexander Gozman, Michele Maio
Journal: Cancer Research (2025)

Abstract Background: Early data suggest poly (ADP-ribose) polymerase inhibitor (PARPi)/anti-PD-[L]1 synergy in homologous recombination repair-mutated (HRRm) or homologous recombination deficient (HRD) cancers. KEYLYNK-007 (NCT04123366) is a tumor-agnostic trial that evaluated the PARPi olaparib plus pembrolizumab in HRRm/HRD advanced tumors. Methods: This phase 2 trial enrolled participants (pts) with HRRm or HRD+ advanced solid tumors to 3 cohorts: BRCAm (except breast and ovarian), non-BRCA HRRm, and non-HRRm HRD. HRRm/HRD was centrally confirmed using the Lynparza HRR-HRD Assay before treatment with 300 mg olaparib BID + 200 mg pembrolizumab Q3W (≤35 cycles). Primary endpoint was ORR per RECIST 1.1 by central review. Secondary endpoints were duration of response and PFS per RECIST 1.1 by central review, OS, and safety. Results: At data cutoff (May 16, 2024), 332 pts were enrolled (n = 132 [BRCAm], n = 104 [non-BRCA HRRm], n = 96 [non-HRRm HRD]) (Table). Median follow-up was 13.4 (BRCAm), 10.4 (non-BRCA HRRm), and 10.8 months (non-HRRm HRD). ORR was 27% (BRCAm), 12% (non-BRCA HRRm), and 12% (non-HRRm HRD). Confirmed RECIST 1.1 responders beyond PARPi-approved indications included pts with advanced breast, ovarian, pancreatic, urothelial, renal, biliary, cervical, esophageal SCC, CRC, gastroesophageal adenocarcinoma, duodenal, small intestine, thyroid, salivary gland, HNSCC, NSCLC, SCLC, leiomyosarcoma, and other sarcomas. There were also multiple responses in HRRm prostate cancer. Grade ≥3 drug-related adverse events occurred in 30% pts; 1/332 (0.3%) pt died from septic shock. Conclusions: In this tumor-agnostic trial, olaparib plus pembrolizumab showed promising durable antitumor activity and manageable safety in HRRm and HRD+ (particularly BRCAm) advanced cancers beyond currently approved indications. Biomarker analysis is ongoing for other predictive biomarkers of response. Citation Format: Timothy A. Yap, Ronnie Shapira-Frommer, Iwona Lugowska, Tudor Ciuleanu, Miguel Quintela-Fandino, Özgür Özyılkan, Serhii Lysenko, Akira Hirasawa, Simcha Pollack, Rachel Salisbury, Alexander Gozman, Michele Maio. KEYLYNK-007: Tumor agnostic trial of olaparib plus pembrolizumab in homologous recombination repair mutation- and homologous recombination deficiency- positive advanced cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT004.
Tissue Engineering and Regenerative Medicine: Perspectives and Challenges
Authors: Van T. Hoang, Quyen Thi Nguyen, Trang Thi Kieu Phan, Trang H. Pham, Nhung Thi Hong Dinh, Le Phuong Hoang Anh, Lan Thi Mai Dao, Van Dat Bui, Hong‐Nhung Dao, Duc Son Le, Anh Thi Lan Ngo, Quang‐Duong Le, Liem Nguyen Thanh
Journal: MedComm (2025)

ABSTRACT From the pioneering days of cell therapy to the achievement of bioprinting organs, tissue engineering, and regenerative medicine have seen tremendous technological advancements, offering solutions for restoring damaged tissues and organs. However, only a few products and technologies have received United States Food and Drug Administration approval. This review highlights significant progress in cell therapy, extracellular vesicle‐based therapy, and tissue engineering. Hematopoietic stem cell transplantation is a powerful tool for treating many diseases, especially hematological malignancies. Mesenchymal stem cells have been extensively studied. The discovery of induced pluripotent stem cells has revolutionized disease modeling and regenerative applications, paving the way for personalized medicine. Gene therapy represents an innovative approach to the treatment of genetic disorders. Additionally, extracellular vesicle‐based therapies have emerged as rising stars, offering promising solutions in diagnostics, cell‐free therapeutics, drug delivery, and targeted therapy. Advances in tissue engineering enable complex tissue constructs, further transforming the field. Despite these advancements, many technical, ethical, and regulatory challenges remain. This review addresses the current bottlenecks, emphasizing novel technologies and interdisciplinary research to overcome these hurdles. Standardizing practices and conducting clinical trials will balance innovation and regulation, improving patient outcomes and quality of life.
Abstract CT170: ALTAS: A phase II trial of anlotinib in combination with TAS-102 in patients with metastatic colorectal cancers
Authors: Qing Liu, Chi Zhang, Xiaojing Xu, Yiyi Yu, Tianshu Liu
Journal: Cancer Research (2025)

Abstract Background: The management of metastatic colorectal cancer (mCRC) in late-line settings remains a formidable challenge, as existing therapies yield limited clinical benefits. The SUNLIGHT trial, which evaluated TAS-102 in combination with bevacizumab, reported a median progression-free survival (PFS) of 5 months and an objective response rate (ORR) of 6.3%. Anlotinib, a multi-target tyrosine kinase inhibitor, has shown promising efficacy and safety profiles across various tumor types. This study aims to explore the potential of combining anlotinib with TAS-102 as a third-line treatment for mCRC patients. Methods: In this open-label, single-arm phase 2 study, mCRC patients who had experienced disease progression following at least two prior standard treatment regimens were enrolled. Patients received a combination of anlotinib (12 mg, PO, QD, days 1-14, q3w) and TAS-102 (35 mg/m2, PO, BID, days 1-5, q2w). The primary endpoint was the ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and safety. Results: As of December 30, 2024, twenty-one patients with mCRC were enrolled in the trial. The median age was 62 years (range: 36-78), with 71.4% male participants. All patients received the combination therapy of anlotinib and TAS-102. Among the 20 evaluable patients, 2 achieved a partial response (PR), 17 experienced stable disease (SD), and 1 exhibited progressive disease (PD) at the first evaluation. The objective response rate (ORR) was 10% (2/20), while the disease control rate (DCR) reached 95.0% (19/20). Based on Kaplan-Meier estimates, the median PFS was 5.6 months. The most common grade ≥3 treatment emergent adverse event (TEAEs) included neutropenia (25%) and decreased platelet count (5%). Conclusions: The combination of anlotinib and TAS-102 has shown promising efficacy and manageable safety, suggesting its potential as a favorable late-line treatment option for mCRC. Clinical trial information: ChiCTR2400079535 Citation Format: Qing Liu, Chi Zhang, Xiaojing Xu, Yiyi Yu, Tianshu Liu. ALTAS: A phase II trial of anlotinib in combination with TAS-102 in patients with metastatic colorectal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT170.
Abstract CT185: Trispecific EGFR x cMET x VEGF antibody, TAVO412, has clinical responses in esophageal and lung cancers
Authors: Mark Chiu, Wei Zhang, Yanjiao Yu, Helen Jiang, Chao Han
Journal: Cancer Research (2025)

Abstract Background: Abnormal EGFR signaling, increased cMET activation, and VEGF-induced angiogenesis are responsible for the growth and metastasis of many difficult to treat solid tumors. TAVO412 is a humanized multi-specific antibody with two distinct anti-EGFR nanobody-like domains, an anti-cMET Fab arm, and an anti-VEGF ScFv domain. In addition, the Fc domain allows for the heterodimerization, antibody-like pharmacokinetic profile, and additional mutations that enhance the Fc effector functions. TAVO412 had strong in vivo tumor growth inhibition in the preclinical models of NSCLC, gastrointestinal and esophageal cancers, PDAC, TNBC, and other solid tumor models. TAVO412 also had strong tumor growth inhibition as demonstrated against NSCLC patient derived xenograft (PDX) models with various mutant EGFR and cMet genotypes. Stronger activities were also demonstrated when TAVO412 was in combination with docetaxel, TKIs, and with radiotherapy. Methods: The clinical study (TAVOTEK412-CN001) is a two-part, open-label, non-randomized, Phase I study to determine the safety and tolerability, to define the MTD/RP2D, and to assess the preliminary efficacy of TAVO412 in patients with advanced or metastatic solid tumors who progressed on prior standard-of-care therapies (Clinical trial NCT06761651). Part 1 of the study is a dose escalation by a standard 3+3 design, mainly for safety and tolerability with 5 dose cohorts up to 1500 mg. Part 2 of the study is an extension of the study in about 100 patients based on the preliminary information obtained in Part 1 regarding dose levels, type of tumor showing preliminary efficacy signals, and genetic makeup. At the time of this abstract, 25 patients with a variety of solid tumors have been enrolled in Part 1 dose escalation. Since no DLT have been observed and MTD has not been reached, an additional dose level at 1750 mg will be tested. Meanwhile, the safety and efficacy signals are being enhanced by the backfill of patients to the safe and potential efficacious dose cohorts starting Q1 2025. The Part 2 of the study is expected to start in Q4 2025. Keywords: trispecific antibody, EGFR, cMET, VEGF, gastrointestinal cancers, lung cancersEthics approval: “This study was approved by CRADL-Suzhou’s Ethics Board; approval number P202302160002.NMPA IND Approval number 2023LP01660; Henan Cancer Hospital Ethics Board approval number 2023-314-003 Citation Format: Mark Chiu, Wei Zhang, Yanjiao Yu, Helen Jiang, Chao Han. Trispecific EGFR x cMET x VEGF antibody, TAVO412, has clinical responses in esophageal and lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT185.
Risk of colorectal cancer and cancer‐related mortality in type 2 diabetes patients treated with metformin, SGLT‐2 inhibitors, or their combination
Authors: Xianhua Mao, Ka‐Shing Cheung, Jing‐Tong Tan, Lung‐Yi Mak, Chi‐Ho Lee, Ho Ming Cheng, Rex Wan‐Hin Hui, Esther Wai Yin Chan, Philip Leung‐Ho Yu, Man‐Fung Yuen, Wai K Leung, Wai‐Kay Seto
Journal: Cancer Communications (2025)
Intratumoral microbiota predicts the response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer
Authors: Yilin Chen, Lu Yang, Yuhong Huang, Teng Zhu, Liulu Zhang, Minyi Cheng, Cangui Wu, Peiyong Li, Minting Liang, Xiaoqi Zhang, Hao Peng, Kun Wang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Neoadjuvant immunotherapy combined with chemotherapy (Chemo-IM) is associated with significantly improved pathological complete response (pCR) rates and long-term survival outcomes in patient with early-stage triple-negative breast cancer (TNBC). However, only a small proportion of patients benefit from the addition of immunotherapy. Here, we explored and confirmed the role of intratumoral microbiota in screening patients with TNBC who are likely to benefit from neoadjuvant Chemo-IM. Methods Patients with previously untreated, non-metastatic TNBC receiving neoadjuvant Chemo-IM were enrolled. Differences in the intratumoral microbiota between the pCR and non-pCR groups were explored via 16S rDNA sequencing (16S-seq). Single-cell transcriptome sequencing (scRNA-seq) was employed to profile the tumor microenvironment (TME). Moreover, correlations between the intratumor microbiota and the TME were explored. Finally, machine-learning models based on the intratumoral microbiota were constructed to predict pCR. Results A total of 89 female patients with early-stage TNBC treated by neoadjuvant Chemo-IM were enrolled. We found that the pCR group had greater diversity and a higher load of intratumoral microbiota than the non-pCR group. Intriguingly, scRNA-seq revealed significantly increased T cell infiltration and decreased tumor-associated macrophage infiltration into tumors in the pCR group. Moreover, intratumoral microbiota load was positively associated with CD4 + CXCL13 + T cell infiltration and negatively associated with CD68 + SPP1 + macrophage infiltration. Combined analysis of 16S-seq and scRNA-seq data revealed that intratumoral microbiota were present in both cancer and immune cells. Finally, we developed a model incorporating intratumoral microbiota and clinicopathological characteristics, and it showed strong power for predicting pCR to neoadjuvant Chemo-IM. Conclusions Intratumoral microbiota may serve as a strong and specific predictor of the response of patients with early-stage TNBC to neoadjuvant Chemo-IM. Our findings could contribute to the development of individualized Chemo-IM strategies for treating TNBC.
Onset and progression of atherosclerosis in patients with melanoma treated with immune checkpoint inhibitors
Authors: Daan C H van Dorst, Tom J J Uyl, Astrid A M Van der Veldt, Timy Andrawes, Arjen Joosse, Esther Oomen-De Hoop, Alexander Hj Danser, Ron H J Mathijssen, Daniel Bos, Jorie Versmissen
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immune checkpoint inhibitors (ICIs) are effective anticancer agents but significantly increase cardiovascular risk. This could be due to its potential to induce or worsen atherosclerosis. We evaluated the onset and progression of atherosclerosis during ICI treatment in patients with melanoma and investigated risk factors for substantial (&gt;10%/year) atherosclerotic plaque growth in five segments of the arterial tree. Methods Onset and yearly progression of atherosclerosis were assessed in the aortic arch, descending thoracic aorta, abdominal aorta, left and right iliac arteries via CT scans performed prior to and 1 year (±3 months) after ICI therapy initiation in patients with melanoma in the adjuvant (resected melanoma) and advanced disease (irresectable stage III and stage IV) setting. The primary outcome was defined as yearly progression of maximal plaque thickness in each arterial segment. Secondary outcomes were changes in the number of plaques, incidence of arterial thrombosis (ATE), and factors associated with substantial plaque growth in the descending thoracic aorta. Results In total, 244 patients were included. Plaque thickness increased significantly in all aortic segments, ranging from 3.0% to 8.0% per year (all p&lt;0.001). In 75% of included patients, substantial plaque growth in ≥1 segment occurred. Number of plaques remained identical in 64–86% of arterial segments. Three (1.2%) developed ATE within 1 year after ICI initiation. ICI combination therapy demonstrated a trend towards increased risk of substantial plaque growth compared with monotherapy (OR 2.10 (95% CI, 0.95 to 4.66; p=0.068)), whereas antihypertensive drug usage was associated with a lower risk (OR 0.48 (95% CI, 0.24 to 0.95; p=0.036)). Conclusion The majority of patients with melanoma experience substantial atherosclerotic plaque growth during ICI therapy. The number of plaques remained relatively stable, suggesting that ICIs could particularly affect pre-existing plaques.
Utilization of exosome-based therapies to augment anti-PD-1/PD-L1 therapies
Authors: John S Wang, Samer Yassin, Adam Y Lin
Journal: Journal for ImmunoTherapy of Cancer (2025)

Abstract The development of immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway has significantly transformed the landscape of cancer treatment. However, resistance mechanisms such as alternative immune checkpoints, T-cell exhaustion, low tumor burden, and immunosuppressive cells in the tumor microenvironment can limit therapeutic efficacy. Recent research has highlighted the role of tumor-derived exosomes expressing PD-L1, which may contribute to resistance by locally and systemically suppressing immune responses. Inhibiting exosome secretion has shown promise in enhancing the effectiveness of anti-PD-1/PD-L1 therapies. The therapeutic potential of targeting exosomes to improve PD-1/PD-L1 inhibition is gaining attention, with preclinical studies showing encouraging results. Clinical trials are needed to evaluate the combination of exosome secretion inhibitors with existing checkpoint therapies and provide hope for patients with resistant cancers.