tbuckley/cabot-search huggingface dataset:
GEMINI-Hepatobiliary: A phase 2 study of novel first-line immuno-oncology-based treatments in patients with advanced hepatobiliary cancers.
Authors: Jian Zhou, Ann-Lii Cheng, Masafumi Ikeda, Ho Yeong Lim, Mehmet Akce, Shukui Qin, Do-Youn Oh, Stephen Lam Chan, Jinfeng Xiang, Xiao Qu, Ruifan Xie, Ming Yang, Rakesh Kumar, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2024)

TPS4187 Background: Although targeted therapies and immuno-oncology (IO)-based regimens have improved overall survival (OS) in advanced hepatobiliary carcinomas, long-term survival rates remain unsatisfactory. Early-phase studies have demonstrated the efficacy of volrustomig (volru; anti-PD-1/CTLA-4 bispecific humanized IgG1 monoclonal antibody [mAb]) in patients (pts) with non-small-cell lung cancer (NSCLC) and renal cell carcinoma, and of rilvegostomig (rilve; anti-PD-1/TIGIT bispecific humanized IgG1 mAb) in pts with NSCLC, along with manageable safety profiles. GEMINI-Hepatobiliary (NCT05775159) is a phase 2, open-label, multidrug, multicenter, master protocol study designed to evaluate the preliminary efficacy and safety of novel IO bispecific mAbs as monotherapy or in combination with standard of care anticancer agents in pts with advanced hepatocellular carcinoma (HCC) and biliary tract cancer (BTC). Methods: The GEMINI-Hepatobiliary platform design permits separate independent substudies (Table). Substudy 1 includes treatment-naïve adults (≥18 years) with histologically confirmed advanced HCC not eligible for locoregional therapy, Barcelona Clinic Liver Cancer Stage B/C, Child-Pugh class A 5–6, and an ECOG performance status (PS) of 0–1. Pts will be treated with volru as monotherapy or in combination with bevacizumab or lenvatinib. Primary endpoints for Substudy 1 are safety and objective response rate (ORR) per RECIST v1.1 by investigator’s assessment. Substudy 2 includes treatment-naïve adults with locally advanced or metastatic, histologically confirmed BTC and an ECOG PS of 0–1. Pts will be treated with gemcitabine + cisplatin with either rilve or volru. Primary endpoints for Substudy 2 are safety and progression-free survival (PFS) per RECIST v1.1 by investigator’s assessment. Secondary endpoints for both substudies include duration of response, disease control rate, ORR, PFS, OS, pharmacokinetics, and immunogenicity. While there are no formal statistical comparisons or hypothesis testing, sample sizes were selected to provide adequate precision for the primary endpoints. The study is currently recruiting at sites in the US, Asia, and Europe. GEMINI-Hepatobiliary master protocol design. Clinical trial information: NCT05775159 . [Table: see text]
A randomized, multicenter, open-label phase III trial of hyperthermic intraperitoneal chemotherapy in platinum-resistant recurrent ovarian cancer (KOV-HIPEC-02).
Authors: Myong Cheol Lim, Ji Hyun Kim, Eun Young Park, Dae Hoon Jeong, Yoo-Young Lee, Chel Hun Choi, Sungjong Lee, Shin-Wha Lee, Jeong-Yeol Park, Se Ik Kim, Jong Chul Baek, Hyeong In Ha, Yong Jung Song, Seob Jeon, Taek Sang Lee, Hye won Jeon, Ki Hyung Kim, Sang-Yoon Park
Journal: Journal of Clinical Oncology (2024)

TPS5635 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery has emerged to achieve a higher concentration of chemotherapeutic agents and treat micro-metastases on peritoneal surfaces. At advanced staged ovarian cancer treated with neoadjuvant chemotherapy, HIPEC during interval cytoreductive surgery with cisplatin 75-100mg/m 2 increases progression-free survival and overall survival (OV-HIPEC-01 and KOV-HIPEC-01). In chemotherapy-naïve ovarian cancer patients, survival benefit is not identified with HIPEC (KOV-HIPEC-01). And the meta-analysis revealed the survival benefit after recent exposure of chemotherapy. In ovarian cancer, HIPEC is thought to overcome chemotherapy resistance. Methods: This trial (KOV-02) is currently actively enrolling, a multicenter, open-label, 1:1 randomized, phase III trial that will enroll 140 patients in platinum-resistant recurrent epithelial ovarian cancer. The trial is registered on ClinicalTrials.gov (NCT05316181). Institutional review board approval was obtained. The first patient was enrolled on April 07, 2022. The experimental arm will receive cytoreductive surgery and HIPEC (Doxorubicin 35mg/m 2 and mitomycin 15mg/m 2 , 41.5-42.0°C) followed by physician-choice chemotherapy, and the control arm will receive physician-choice chemotherapy until disease progression or intolerable toxicity. The primary objective of the trial is to evaluate progression-free survival (PFS) between the HIPEC group and the control group. Secondary objectives are overall survival (OS), cancer-specific survival, safety, and quality of life. Assuming that the enrollment period is three years and the follow-up period is two years, the total number of events required is 121. Based on the log-rank test, the total number of subjects required to prove HR 0.6 with a two-sided alpha of 0.05 and 80% power is 126. Considering 10% drop-out, 140 patients are finally studied. Clinical trial information: NCT05316181 .
GOG3069: Phase 2 study of alpelisib and fulvestrant for PIK3CA-mutated estrogen receptor (ER)-positive endometrioid endometrial cancers.
Authors: Stephanie Gaillard, Michael Sill, Jennifer Klein, Thomas Reid, Michael Callahan, Julia Fehniger, Janelle Sobecki, Michael A. Gold, Thomas J Herzog, Brian M. Slomovitz, Ursula A. Matulonis
Journal: Journal of Clinical Oncology (2024)

TPS5639 Background: Treatment options for persistent, metastatic, or recurrent endometrial cancer continues to evolve as we learn more about the molecular landscape of this disease. Recent studies have shown a benefit to endocrine-based combinations such as aromatase inhibitors with mTOR or CDK4/6 inhibitors especially in patients who had not received prior chemotherapy ( 1– 3). The presence of oncogenic PIK3CA mutations have been shown to impact response to aromatase inhibitors in breast cancer. The combination of alpelisib and fulvestrant was approved for the treatment of metastatic hormone receptor-positive, HER2-negative breast cancer harboring oncogenic mutations in the PIK3CA gene that progressed on prior endocrine therapy( 4). PIK3CA mutations are commonly identified in endometrial cancers and may similarly confer endocrine resistance. GOG3069 is a phase II trial designed to evaluate the efficacy and safety of alpelisib and fulvestrant in a biomarker-selected endometrial cancer patient population. Methods: This is a phase II non-randomized, open label, multicenter, two-stage study. Eligible patients must have advanced (FIGO 2014 Stage III or IV), persistent, or recurrent endometrial carcinoma with measurable disease by RECISTv1.1 criteria. Patients cannot be curable by surgery or radiotherapy. Disease must be of endometrioid histology with positive expression of estrogen receptor (defined as ≥1% of tumor cells demonstrating positive nuclear staining by immunohistochemistry) and oncogenic PIK3CA mutation. Patients may have received no more than 3 prior lines of therapy including 1 prior line of systemic chemotherapy. Enrolled patients will receive treatment with alpelisib 300mg orally daily and fulvestrant 500mg IM on Day 1 and Day 15 of Cycle 1, then 500mg IM on Day 1 of each 28-day cycle. The primary endpoint is overall response rate as measured by RECISTv1.1-defined tumor response. Secondary endpoints include safety, tolerability, progression-free survival, duration of response, and 24-month overall survival rate. GOG3069 activated in November 2023 and expects to enroll across 15 US sites. The statistical plan uses a conditional stratified design factoring differing probabilities of response based on whether the patient had prior chemotherapy exposure. ClinicalTrials.gov Identifier: NCT05154487 References: 1. B. M. Slomovitz et al., Gynecologic Oncology. 164, 481–491 (2022); 2. P. A. Konstantinopoulos et al., J Clin Oncol. 41, 599–608 (2023); 3. G. Colon-Otero et al., ESMO Open. 5, e000926 (2020); 4. F. André et al., N Engl J Med. 380, 1929–1940 (2019). Clinical trial information: NCT05154487 .
ESORES-Trial: Surgery as needed versus surgery on principle in patients with postneoadjuvant clinical complete tumor response of esophageal cancer.
Authors: Julian Hipp, Christiane J. Bruns, Claudia Schmoor, Joachim Weis, Jens Hoeppner
Journal: Journal of Clinical Oncology (2024)

TPS4185 Background: A substantial fraction of patients with esophageal cancer (EC) shows post-neoadjuvant pathological complete response (pCR). Principal esophagectomy after neoadjuvant treatment is the standard of care for all patients. Active surveillance (AS) and surgery as needed may be a treatment alternative for patients with clinical complete response (cCR). Methods: ESORES is a multicenter randomized controlled parallel-group non-inferiority trial. Patients are randomized either to surgery on principle and subsequent follow-up (Arm B) or clinical response evaluation (CRE) and surgery as needed (Arm A). CRE consists of esophagogastroscopy with deep biopsies (EGD), endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) of suspicious lymph nodes, and F18-FDG-PET CT. In case of residual tumor (non-CR) after CRE, treatment is surgery. Patients with cCR will proceed with AS and surgery only if local regrowth occurs. AS comprises EGD, EUS-FNA and CT-Thorax/Abdomen at 3/6/9/12/18/24 months and yearly thereafter. A sample size of 670 patients is needed to demonstrate non-inferiority of Arm A vs. Arm B with regard to overall survival (OS) at a one-sided significance level of 5%, choosing a hazard ratio of 1.325 as non-inferiority margin which corresponds to a difference in 3-year OS rates of 8%. Superiority with regard to quality of life will be evaluated hierarchically only after non-inferiority with respect to OS has been shown. Key inclusion criteria: histologically verified EC, TNM stage ycT0-3 ycN0 ycM0, completion of neoadjuvant chemotherapy (nCT) or chemoradiation (nCRT) (irrespective of specific protocol), no visible lymphatic or distant metastasis in routine postneoadjuvant CT. Key exclusion criteria: postneoadjuvant dysphagia and/or esophageal obstruction, tumors of the cervical esophagus, tumors with direct proximity to the membranous part of the central airways (if regrowth is suspected to evoke locally irresectable ryT4b-stage), TNM stage cT4/ycT4 and/or cM1/ycM1, tumor progression during/after nCT/nCRT, and nCRT with &gt;50 Gy radiation dose. Primary endpoints (hierarchically tested): 1) OS, 2) EORTC QLQ C30 global quality of life subscale. Secondary endpoints: Efficacy: long term tumor control, disease free survival, distant metastasis/local recurrence/regional recurrence; quality of life: EORTC QLQ C30, QLQ OES18, fear of progression: FoP-Q-12, surgery-free survival time in Arm A, patients’ satisfaction: EORTC OUT-PATSAT7; economic impact: days and costs of hospitalization; Safety: Interventional Safety: 3-Year-Comprehensive Complication Index, Oncological Safety (diagnostic accuracy of CRE, resection status (R0/R1/R2), irresectable regrowth during AS). Enrollment of patients started on January 30 th , 2024. Clinical trial information: DRKS00032613 .
EFFECT-neo: A phase 3 study of pembrolizumab plus chemotherapy versus chemotherapy as neoadjuvant therapy in patients with resectable locally advanced head and neck squamous cell carcinoma.
Authors: Yang Zhang, Wei Guo, Wenchao Zhang, Zhenyu Wang, Kai Yu, Li Li, Yan Wang, Zhigang Huang
Journal: Journal of Clinical Oncology (2024)

TPS6123 Background: There is still a huge need for treatment of operable locally advanced head and neck squamous cell carcinoma (LA HNSCC). Multiple phase 2 studies have shown that PD-1 combined with chemotherapy has good short-term efficacy, especially the pathological complete response (pCR) rate exceeds 30%, which is also considered to be an important factor in the survival benefit that neoadjuvant immune therapy may bring. The randomized, open-label, phase 3 EFFECT-neo study (NCT06102395) will evaluate efficacy and safety of pembrolizumab plus chemotherapy versus chemotherapy as neoadjuvant therapy in patients with resectable LA HNSCC. Methods: Patients with untreated LA HNSCC who met the inclusion criteria will be randomly assigned 1:1 to two treatment arms. Experimental group will be given 2 cycles of pembrolizumab (200mg d1, Q3W) + chemotherapy (perfer TPF regimens) . Control group will undergo 2 cycles of chemotherapy. Both two arms should finish imaging evaluation, and If the result is CR after neoadjuvant treatment, radiotherapy (RT) (60-70Gy) ± chemotherapy (investigator's choice) will be given as adjuvant treatment; if the result are PR or SD, surgery (within 2 weeks) will be performed, and then RT ± chemotherapy will be given. If the imaging evaluation is PD, patients will be received standard treatment. Enrolled patients must closely monitor the adverse reactions of chemotherapy and record the time, grade, treatment measures, outcomes, etc. All patients will be reviewed every 3 months for 1 year; after 1 year, they were reviewed every 6 months for 3 years; patient recurrence and survival data were recorded. Eligibility criteria will include age ≥18 years; untreated with immunotherapy, resectable, stage III/IVB HNSCC (AJCC Cancer Staging Manual, 8th edition); ECOG performance status 0-2; and the investigators believe that patients can safely receive pembrolizumab combined with chemotherapy in neoadjuvant chemotherapy. Randomization treatment will continue until disease progression, unacceptable toxicity, or decision to withdraw. Primary end points is pCR, defined as the absence of residual invasive squamous cell carcinoma within the primary tumor specimen on resection/needle biopsy (Patients with CR imaging results will undergo multi-point biopsy). Secondary end points include objective response rate, 1-year and 2-year event-free survival rates, 2-year overall survival rate, functional preservation rate, safety and Karnofsky performance status. Recruitment is ongoing and will continue until 272 patients are enrolled. Clinical trial information: NCT06102395 .
A phase II randomized control trial of triapine plus lutetium 177 DOTATATE versus lutetium 177 DOTATATE alone for well-differentiated somatostatin receptor-positive neuroendocrine tumors.
Authors: Aman Chauhan, Charles Kunos, Susanne M. Arnold, Heidi Weiss, S. Percy Ivy, Steven Gore, Lawrence Rubinstein, Lorraine Pelosof, Jan Hendrik Beumer, Jill Kolesar, William Edgar Carson, Elise C. Kohn, Lowell Brian Anthony
Journal: Journal of Clinical Oncology (2024)

TPS4202 Background: Radiolabeled somatostatin analogues provide a means of delivering targeted radiation with a high therapeutic index to NETs that express somatostatin receptors (SSTRs). Radiolabeled somatostatin analogue Lutetium 177 DOTATATE (Lutathera) is a beta-emitting radionuclide, FDA approved for use in SSTR positive gastroenteropancreatic neuroendocrine tumors (GEPNETS) in the US based on the NETTER-1 Phase III trial. Despite favorable PFS and safety profile, the drug has limited cytoreductive capability with a 14% ORR. Peptide receptor radionuclide therapy (PRRT) also doesn’t seem to be very effective in treating peritoneal disease. We hypothesize that addition of an effective radiation sensitizer could help improve antitumor activity of Lutathera. Radiation is a potent inducer of DNA double-strand breaks, and ribonucleotide reductase (RNR) is the rate-limiting enzyme in the synthesis and repair of DNA, making RNR-targeted therapy a rationale therapeutic strategy for radiosensitization. ETCTN 10388 (NCT04234568) evaluated safety and efficacy of the combination of lutetium 177 DOTATATE, a beta-emitting radionuclide in combination with triapine, a ribonucleotide reductase (RNR) inhibitor. The combination of triapine and Lu-177 DOTATATE was safe with preliminary efficacy signals. Methods: This study is an investigator initiated, NCI sponsored, multicenter randomized phase 2 trial of triapine and lutetium Lu 177 DOTATATE in well-differentiated somatostatin receptor-positive neuroendocrine tumor. A total of 94 patients will be equally randomized to either Lu-177 dotatate or Triapine + Lu-177 dotatate arm. The study will be open through the NCI ETCTN (National Cancer Institute Experimental Therapeutics Clinical Trials Network) program. Triapine will be administered orally from D1-14 with each dose of PRRT [200 mCi]. Primary endpoint is to evaluate overall response rate (ORR). Secondary endpoint is to evaluate median PFS. We are also evaluating triapine PK, plasma deoxyribonucleosides, circulating DNA and plasma hPG80, a novel blood based diagnostic biomarker. Clinical trial information: 05724108.
Clinical relevance of circulating autoantigen-specific T follicular regulatory cells in pemphigus vulgaris
Authors: Jihee Kim, Jong Hoon Kim
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Clinical relevance of circulating autoantigen-specific T follicular regulatory cells in pemphigus vulgaris Get access Jihee Kim, Jihee Kim Department of Dermatology, Yongin Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea https://orcid.org/0000-0002-0047-5941 Search for other works by this author on: Oxford Academic Google Scholar Jong Hoon Kim Jong Hoon Kim Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea Correspondence: Jong Hoon Kim MD, PhD, Email:jhkim074@yuhs.ac https://orcid.org/0000-0002-3385-8180 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae270, https://doi.org/10.1093/bjd/ljae270 Published: 04 July 2024 Article history Received: 17 June 2024 Revision received: 17 June 2024 Accepted: 03 July 2024 Published: 04 July 2024
Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: Results from the bladder cohort of the DESTINY-PanTumor02 (DP-02) study.
Authors: Piotr Jan Wysocki, Kyung Hae Jung, Do-Youn Oh, Deborah Blythe Doroshow, Elena Artamonova, Lemonitsa Mammatas, Po-Jung SU, Vladimir Moiseyenko, Konstantin Penkov, Daniil Stroyakovskiy, Jorge Bartolome, Salvatore Siena, Anitra Fielding, Lindsey Jung, Flavia Michelini, Soham D. Puvvada, Vicky Makker
Journal: Journal of Clinical Oncology (2024)

4565 Background: In DP-02, T-DXd showed robust responses and clinically meaningful survival outcomes in 267 pretreated pts with HER2-expressing solid tumors; the objective response rate (ORR) by investigator (INV) was 37.1% (95% CI 31.3, 43.2). Here we report subgroup analyses in the bladder cohort (urothelial carcinoma including transitional cell carcinoma of the renal pelvis, ureter, urinary bladder, or urethra), and characterize pts with an objective response (OR). Methods: This open-label, Phase 2 study (NCT04482309) evaluated T-DXd (5.4 mg/kg Q3W) in pts with HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced/metastatic disease after ≥1 systemic treatment (Tx), or without Tx options. The primary endpoint was confirmed ORR by INV. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), and safety. Exploratory endpoints included efficacy outcomes according to HER2 expression. Results: At data cutoff (June 2023), 41 pts with urothelial cancers had received T-DXd (median [m] follow up [range]: 12.65 [0.4–26.8] months); 27 (65.9%) had received ≥2 prior Tx regimens. 16/41 pts (39.0%; 95% CI 24.2, 55.5) had a confirmed OR by INV; 12 responders had received ≥2 prior Tx regimens, 14 had received prior immunotherapy Tx, and 14 had known PD-L1 immune cell status ≥1%. The Table shows efficacy outcomes in all pts and by HER2 expression (central testing). Grade (G) ≥3 drug-related adverse events occurred in 17/41 (41.5%) pts. Adjudicated drug-related interstitial lung disease / pneumonitis occurred in 4/41 (9.8%) pts (n=1 G1; n=3 G2). Conclusions: T-DXd showed clinically meaningful responses in pretreated pts with urothelial cancers, including across HER2 expression levels (IHC 3+ and 2+). Safety was consistent with the known profile. These data support further evaluation of T-DXd as a potential Tx for pretreated pts with HER2-expressing urothelial cancers. Clinical trial information: NCT04482309 . [Table: see text]
REPLACE: A phase III, randomized, open-label trial to evaluate the safety and efficacy of regorafenib and pembrolizumab versus locoregional therapy (LRT) with transarterial chemoembolization (TACE) or transarterial radioembolization (TARE), for the first-line treatment of intermediate-stage hepatocellular carcinoma (HCC) with beyond up-to-7 criteria.
Authors: Peter Robert Galle, Masatoshi Kudo, Josep M Llovet, Ann-Lii Cheng, Riccardo Lencioni, Yanina Oviedo, Kalpna Desai, Amandine Monier, Richard S. Finn
Journal: Journal of Clinical Oncology (2024)

TPS4200 Background: Intermediate-stage HCC represents a heterogeneous population, posing unique challenges for therapeutic management. With the advent of effective systemic therapies for unresectable HCC, the treatment landscape for intermediate-stage extends beyond LRT, particularly in patients with high tumor burden. The growing evidence about the benefit of systemic therapy in intermediate-stage HCC led to the inclusion in some recent guidelines of systemic therapy as the first choice of treatment in TACE-unsuitable patients with intermediate-stage HCC. Despite these recommendations, no randomized clinical trial has been published comparing LRT with TACE/TARE versus systemic therapy in patients with intermediate-stage HCC and high tumor burden. Methods: REPLACE is a phase III, multicenter, randomized, open-label trial that will compare the efficacy and safety of LRT with TACE/TARE versus systemic therapy, for the first-line treatment of intermediate-stage HCC with beyond up-to-7 criteria. Eligible participants will be randomized 1:1 to receive regorafenib (90 mg orally q.d. on days 1 to 21 of a 4-week cycle), and pembrolizumab (400 mg i.v. on day 1 of a 6-week cycle) or LRT with TACE or TARE, and will be stratified according to geographic region (Asia vs. non-Asia), ECOG Performance Status (0 vs 1) and Albumin-Bilirubin (ALBI) grade (1 vs 2). Patients must have intermediate-stage HCC with beyond up-to-seven criteria (Up-to-7 criteria = largest tumor diameter (cm) + number of tumors ≤7), measurable disease per RECIST 1.1, disease not amenable to curative treatment but amenable to LRT with TACE or TARE, no prior systemic or LRT for HCC, except for successful resection and/or ablation completed ≥ 6 months prior to randomization. Patients will be treated until progressive disease, unacceptable toxicity, or other treatment discontinuation criteria is met. The primary endpoint is progression free survival (PFS), assessed locally by the Investigator using mRECIST for HCC. Secondary endpoints include PFS assessed locally by the Investigator using RECIST 1.1; PFS centrally assessed using mRECIST and RECIST 1.1; overall survival; overall response rate according to RECIST v.1.1 and mRECIST based on the Investigator’s and central assessment; time to unTACEable progression; duration of response; safety and tolerability of the trial treatments, and patient reported outcomes for health-related quality of life. The estimated enrollment is 496 patients from approximately 14 countries. Recruitment started in October 2023 and is currently ongoing. Clinical trial information: NCT04777851 .