bluuebunny/crossref_metadata_2025_split huggingface dataset:
MOUNTAINEER-03: Phase 3 study of tucatinib, trastuzumab, and mFOLFOX6 as first-line treatment in HER2+ metastatic colorectal cancer—Trial in progress.
Authors: Bekaii-Saab Tanios S. , Van Cutsem Eric , Tabernero Josep , Siena Salvatore , Yoshino Takayuki , Nakamura Yoshiaki , Raghav Kanwal Pratap Singh , Cercek Andrea , Heinemann Volker , Adelberg David E. , Ward James Edward , Yang Shan , Andre Thierry , Strickler John H 
Published: January 2023

TPS261 Background: Current standard of care (SOC) for treatment (tx) of metastatic colorectal cancer (mCRC) is multi-agent chemotherapy, w/ or w/o a VEGF- or EGFR-inhibitor. HER2 is a validated clinical target in breast and gastric cancers. HER2 amplification occurs in 3%-5% of patients (pts) w/ mCRC; the rate of HER2 amplification can increase to ~10% in pts w/ RAS/BRAF wild-type mCRC tumors. Tucatinib (TUC), a highly selective, HER2-directed tyrosine kinase inhibitor, is approved in multiple regions for HER2+ metastatic breast cancer and is being investigated in gastrointestinal cancers. MOUNTAINEER (NCT03043313) evaluated the safety and efficacy of TUC and trastuzumab (Tras) in pts w/ tx refractory RAS wild-type, HER2+ mCRC. Results from the primary endpoint analysis showed clinically meaningful activity (confirmed ORR of 38.1% and median DOR of 12.4 months) and demonstrated TUC + Tras was well tolerated with a low discontinuation rate (5.8%) and no deaths due to AEs. MOUNTAINEER-03 will further investigate TUC in combo w/ mFOLFOX and Tras in pts w/ RAS wild-type, HER2+ mCRC. Methods: MOUNTAINEER-03 (NCT05253651) is a global, open label, randomized, phase 3 study for 1L tx of HER2+ and RAS wild-type mCRC. Approximately 400 pts will be randomized 1:1 to the TUC experimental arm (TUC [300 mg PO BID] + Tras + mFOLFOX) or the SOC arm (mFOLFOX alone or in combo w/ either bevacizumab or cetuximab). HER2 status is determined centrally w/ tissue based HER2 immunohistochemistry and in situ hybridization assays. Eligible pts must not have received prior tx in the metastatic setting but may have received adjuvant tx if completed > 6 months prior to enrollment. Pts must be ≥18 years of age w/ an ECOG performance status of ≤1 and RAS wild-type mCRC. Pts w/ treated stable central nervous system metastases are eligible. Randomization is stratified by primary tumor location (left-sided vs other) and liver metastases (presence/absence). Primary endpoint is progression-free survival per RECIST v1.1, assessed by blinded independent central review (BICR). Key secondary endpoints are overall survival and confirmed objective response rate per RECIST v1.1 assessed by BICR. Enrollment is ongoing in the US, w/ global sites planned. Clinical trial information: NCT05253651 .
Patient-reported outcomes (PROs) and biomarker assessments in daNIS-3, a phase II platform study of NIS793 (anti–TGF-β monoclonal antibody) and other investigational drug combinations with standard of care (SOC) vs SOC alone in patients (pts) with second-line metastatic colorectal cancer (mCRC).
Authors: Kopetz Scott , Kasper Stefan , Rivera Fernando , Tournigand Christophe , Cheng Yuan , Deshpande Priya , D'Alessio Denise , Amirouchene Angelozzi Nabil , Bento Pereira da Silva Ana , Segal Neil Howard 
Published: January 2023

TPS272 Background: Despite the utilization of systemic targeted agents with chemotherapy for mCRC, long-term survival remains poor. Disease progression in mCRC is common, and SOC options are associated with reduced quality of life (QoL) that has been negatively associated with survival. Here, we present daNIS-3, a Phase II, randomized, open-label platform study (NCT04952753) of NIS793 and other investigational drug combinations in pts with second-line mCRC, with an emphasis on the exploratory PROs and biomarker assessments. Methods: Eligible pts are adults with microsatellite-stable mCRC who have progressed on or within 6 months of one prior line of systemic therapy for mCRC and are not amenable to potentially curative surgery. Pts are treated with NIS793 (Day [D]1 ± D15; 2100 mg) + SOC (D1 + D15; bevacizumab [5 mg/kg] + FOLFIRI/mFOLFOX6) +/- tislelizumab (D1; 300 mg), or SOC alone. All drugs are administered intravenously on 28-day cycles. Each investigational arm begins with a safety run-in involving ≥6 eligible pts; safety run-in of the tislelizumab arm follows completion of the NIS793 + SOC safety run-in. Following confirmation of the recommended dose, pts are randomized (2:1) in the expansion part to receive investigational drug(s) + SOC (n≈75) or SOC alone (n≈38). Exploratory objectives include PROs (expansion part only) and biomarker assessments. PRO measures (EORTC-QLQ-C30, QLQ-CR29, PRO-CTCAE, and FACT-GP5) will be collected electronically throughout the study and used to explore pt-reported disease symptoms, health-related QoL, functioning, and treatment-related side effects. Potential biomarkers of response and mechanisms of resistance will be assessed in tumor and blood samples. Baseline archival/tumor biopsies will be collected to assess the correlations between clinical response and molecular subtype, tumor mutational burden, TGF-β gene signatures, and immune-related biomarkers. Optional biopsies during Cycle 3 and at the end of treatment will be used to assess pharmacodynamic effects of NIS793 on the tumor microenvironment and resistance mechanisms, respectively. Circulating tumor DNA and cytokine and TGF-β levels will be continuously monitored through serial blood samples to evaluate treatment benefit, correlate alterations with response, and assess the effect(s) of NIS793. An additional blood sample for nucleic acid analysis will evaluate the effect(s) of TGF-β blockade. The daNIS-3 study started on November 15, 2021, and plans to recruit approximately 266 pts from 77 sites across 19 countries. Clinical trial information: NCT04952753 .
Randomized phase 2 study of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus FOLFIRI/FOLFOX and bevacizumab as second-line treatment of advanced colorectal cancer (DeFianCe).
Authors: Wainberg Zev A. , Boccia Ralph V. , Strickler John H , Moehler Markus H. , Sirard Cynthia A. , Walsh Erin K , Parker Elizabeth C , Lee Keun-Wook 
Published: January 2023

TPS275 Background: Colorectal cancer is the third most prevalent cancer, and the prognosis of patients with advanced metastatic (mCRC) is poor. The efficacy of standard of care (SOC) second-line chemotherapy combinations with anti-vascular endothelial growth factor (VEGF) therapies remains modest. Previously treated advanced mCRC that is microsatellite stable (MSS/pMMR) represents nearly 95% of the metastatic population and remains a high unmet medical need. DKN-01 is a humanized IgG4 monoclonal antibody (mAb) targeted against Dickkopf-related protein 1 (DKK1), a regulator of the Wnt signaling pathway. DKK1 has been identified as a potential oncogenic driver in CRC and has been correlated with 5FU resistance. Therefore, DKK1 expression is a potential predictive biomarker for chemotherapeutic resistance in CRC. Methods: This is a phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate safety and efficacy of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus SOC [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced mCRC patients. In Parts A and B, approximately 150 advanced MSS, BRAF Wild Type mCRC patients with radiographic progression during or following 1 prior line of systemic treatment will be enrolled in the study. Part A is a safety run-in with DKN-01 plus FOLFIRI/FOLFOX and bevacizumab in at least 20 safety evaluable patients. In Part B, approximately 130 patients will be randomized 1:1 to either the experimental (DKN-01 plus FOLFIRI/FOLFOX and bevacizumab) or control arm (FOLFIRI/FOLFOX and bevacizumab), using a central stratified block randomization scheme and stratified based on DKK1 RNAscope tumor percentage score (TPS) (≥1% vs <1%). Primary endpoint is progression free survival and secondary endpoints include overall response rate, duration of response, overall survival and incidence of ≥Grade 3 related treatment-related adverse events (TRAEs). Exploratory endpoints will include evaluation of efficacy outcomes based upon tumoral DKK1 expression. Recruitment is ongoing. Clinical trial information: NCT05480306 .
RELATIVITY-123: A phase 3, randomized, open-label study of nivolumab (NIVO) + relatlimab (RELA) fixed-dose combination (FDC) versus regorafenib or trifluridine + tipiracil (TAS-102) in later-line metastatic colorectal cancer (mCRC).
Authors: Feeney Kynan , Joubert Warren Lance , Bordoni Rodolfo Eduardo , Babu Sunil , Marimuthu Sathiya , Hipkin Bill , Huang Liping , Tam Rachel , Acosta Rivera Mirelis 
Published: January 2023

TPS278 Background: The standard of care (SoC) for first-line management of non-microsatellite instability-high/deficient mismatch repair (non-MSI-H/dMMR; also referred to as microsatellite-stable/proficient MMR) mCRC includes systemic chemotherapy and targeted agents that improve overall survival (OS). However, in patients (pts) with later-line disease, current SoC treatments (including regorafenib and TAS-102) are associated with poor responses (objective response rates [ORR] < 2%) that are not durable, limited OS (6.4-7.1 months) and substantial toxicity. Immunotherapies targeting programmed death (PD)-1 show promising efficacy in pts with MSI-H mCRC; however, single-agent immunotherapy does not provide benefit for pts with non-MSI-H/dMMR mCRC. Therefore, additional treatment options with an improved benefit-risk profile in pts with later-line non-MSI-H/dMMR mCRC are needed. Emerging data suggest that dual inhibition of LAG-3 and PD-1 has the potential to boost immune surveillance and elicit durable responses in non-MSI-H/dMMR mCRC. RELA is a human immunoglobulin G4 lymphocyte-activation gene 3 (LAG-3)-blocking antibody that enhances the antitumor immune response. Here we describe the RELATIVITY-123 study investigating NIVO + RELA FDC in later-line mCRC. Methods: RELATIVITY-123 (NCT05328908) is a phase 3, randomized (1:1), open-label study to assess NIVO + RELA FDC versus regorafenib or TAS-102 in adult pts with later lines of non-MSI-H/dMMR mCRC. Inclusion criteria include metastatic or recurrent unresectable CRC, recent progression following 1–4 prior lines of treatment (or documented intolerance of prior systemic chemotherapy regimens), ECOG performance status ≤ 1, and measurable disease per RECIST version (v) 1.1. Exclusion criteria include confirmed MSI-H/deficient mismatch repair, prior treatment with an immunotherapy, regorafenib, or TAS-102 and history of significant cardiovascular disease, interstitial lung disease/pneumonitis, or autoimmune disease. Dual primary endpoints are OS in all randomized pts and in randomized pts with PD-L1 CPS ≥ 1. Secondary endpoints include ORR, progression-free survival, and duration of response by blinded independent central review and investigator per RECIST v1.1, safety, and time until definitive deterioration-physical function and -quality of life in all randomized pts and in randomized pts with PD-L1 CPS ≥ 1. The study initiated in April 2022 and is enrolling globally. Clinical trial information: NCT05328908 .
A multicenter randomized controlled trial of esophagectomy with or without prophylactic supraclavicular node dissection: A phase III trial (JCOG2013, MODERN3).
Authors: Tsunoda Shigeru , Tsubosa Yasuhiro , Sasaki Keita , Machida Ryunosuke , Daiko Hiroyuki , Kato Ken , Kitagawa Yuko 
Published: January 2023

TPS474 Background: Supraclavicular lymph nodes (SCLN) have been regarded as regional nodes of thoracic esophageal cancer in Japan and resected along with cervical paraesophageal lymph nodes as a cervical part of the standard three-field dissection, while the involvement of SCLN is regarded as distant metastasis in Western countries. However, there is no clear evidence that supports or rejects prophylactic SCLN dissection. As postoperative SCLN metastasis can often be managed by either surgery or chemoradiotherapy at the time of relapse, routine prophylactic SCLN dissection may not be essential. Here we conduct the clinical trial to confirm the non-inferiority of esophagectomy with D2 lymphadenectomy except for SCLN to standard D2 lymphadenectomy in terms of overall survival (OS) for patients with resectable upper or middle thoracic esophageal cancer. Methods: Eligibility criteria include the followings; upper or middle thoracic esophageal squamous cell carcinoma, adenosquamous carcinoma, or basaloid cell carcinoma with clinical stage I, II, III, or IVA (except for T4) based on the 8th UICC-TNM, age 18 to 80, ECOG performance status 0 or 1, and adequate organ function. Neoadjuvant chemotherapy (cisplatin plus 5- fluorouracil or docetaxel plus cisplatin plus 5-fluorouracil) is allowed, but preoperative chemoradiotherapy is not allowed. Patients are randomly assigned to the following two arms using the minimization method with a random component to balance institution, clinical stage (Stage I (T1N0M0) versus Stage I (T1N1M0)/II/III/IVA), age (76 or older versus 75 or younger), and tumor location (upper thoracic versus middle thoracic). Patients undergo either esophagectomy with standard D2 dissection (Arm A) or esophagectomy with D2 lymphadenectomy except for SCLN (Arm B). The primary endpoint is OS in all randomized patients. The secondary endpoints are relapse-free survival, the incidence of perioperative and delayed complications, the incidence of SCLN recurrence, the incidence of salvage cervical treatment, the proportion of synchronous cervical and abdominal procedure, and operation time and the number of operating surgeons. A sample size of 456 patients would be required to observe 147 events to demonstrate the non-inferiority of Arm B in terms of OS, with a one-sided alpha of 5%, power of 70%, an accrual period of 5 years, a follow-up period of 3 years, and a non-inferiority margin of 6% at 3-year OS, assuming the expected 3-year OS of Arm A and Arm B are 80% and 81%, respectively. The planned sample size was set at 480 patients (240 patients per arm). This trial was registered at the Japan Registry of Clinical Trials (jRCT) as study number jRCT1030220248 and started in August 2022. Clinical trial information: jRCT1030220248 .
Efficacy and safety of XELOX combined with anlotinib and penpulimab vs XELOX as adjuvant therapy in ctDNA-positive gastric and esophagogastric junction adenocarcinoma: A protocol for a randomized, controlled, multicenter phase II clinical trial—EXPLORING study.
Authors: Chen Yizhang , Tang Jie , Guo Fen , Li Wei , Zhang Jiaguang , Zhang Xinyi , Tian Yitong , Pan Lanlan , Ma Ling , Shu Yongqian , Chen Xiaofeng 
Published: January 2023

TPS486 Background: The clinical benefit of current postoperative adjuvant chemotherapy for gastric adenocarcinoma/gastroesophageal junction adenocarcinoma (GA/GEJA) leaves much to be desired. CtDNA could serve as a potential marker to identify patients (pts) who are most at risk of recurrence. Reinforcing standard adjuvant chemotherapy with immunotherapy has already been indicated to significantly boost clinical benefit, albeit such evidence is rare in GA/GEJA. Here, we intend to prove the clinical benefit of the reinforcement of adjuvant chemotherapy with immunotherapy in patients who are deemed high risk of recurrence by ctDNA analysis, in hope of shedding light on further improvements in adjuvant therapy for GA/GEJA. Methods: This study is designed as a prospective, randomized, controlled, multicenter phase II study in patients histologically or cytologically diagnosed with CG/GEJC (Siewert III), 18-75 years, ECOG PS 0-1, underwent D2 gastrectomy and achieved R0 or R1 resection. Beginning from February 2022, a total of 270 stage III patients will be enrolled and subjected to ctDNA sequencing, and those with positive results will subsequently be randomized 1:1 to arm A or B. CtDNA-negative patients will be assigned to arm C and pts who had ctDNA positive but failed to be randomized will be assigned to arm D. Pts in arm A will receive anlotinib, penpulimab and XELOX for 6-8 cycles, maintained with anlotinib and penpulimab for up to 1 year, while pts in arm B will receive XELOX alone for 6-8 cycles. Pts in arms C&D will receive the investigator’s choice of therapy. Arms A&B will be monitored for ctDNA levels on a 3-month cycle for 1 year. Survival data, laboratory findings, imaging reports and nutritional status will be regularly followed-up in all arms. The primary endpoint is the median disease-free survival (DFS) of arm A versus arm B determined via CT/MRI imaging. Secondary endpoints include the median DFS of arm B versus arm C, the 2- and 3-year DFS rates, overall survival (OS), the impact of hallmark molecules (presumably ctDNA) on the treatment response, adverse events (AEs), and the impact of nutrition status and exercise on recurrence. Clinical trial information: NCT05494060 .
Real-world registry of patients with unresectable hepatocellular carcinoma: The OREIOS study.
Authors: Chan Stephen Lam , Ryu Min-Hee , Waked Imam , Shao Yu Yun , Tai Wai Meng David , Breder Valeriy , Alolayan Ashwaq , Ganguly Sandip 
Published: January 2023

TPS618 Background: A majority of patients with hepatocellular carcinoma (HCC) are diagnosed with unresectable disease due to extensive extrahepatic spread, presence of multifocal tumors, poor hepatic function or tumor location near major intrahepatic vessels. The treatment landscape for unresectable HCC is rapidly evolving with availability of novel agents, mandating evidence-based therapeutic algorithm for optimum clinical outcomes. Integrating newly approved and emerging therapies in this extremely heterogeneous HCC population with coexisting risk factors (performance status, Child-Pugh class, macrovascular invasion or extrahepatic metastases, and alpha-fetoprotein levels) may pose challenge without understanding survival outcomes with the current treatment practices. Also, application of immunotherapy and targeted agents in clinical practice displays significant regional variations. Real-world evidence on the management of unresectable HCC is sparse across different geographies. The OREIOS study aims to describe the management patterns, clinical characteristics, possible predictors, and survival outcomes in patients with unresectable HCC in 12 countries across Asia, Latin America and the Middle East. The data may serve in devising policies on optimal patient selection and sequencing of novel systemic therapies for unresectable HCC. Methods: OREIOS is an ongoing multicenter, retrospective, non-interventional registry in adults diagnosed between 01 January 2017 and 31 December 2019 with unresectable BCLC stage B HCC, ineligible for initial loco-regional therapy or stage C advanced or metastatic disease, with at least 12 months (or until death if it occurs within 12 months of diagnosis) of available records. Patients with BCLC stage D and other concomitant metastatic cancers are excluded. Data collection includes socio-demographics, clinico-pathological characteristics, treatment modalities, survival outcomes, comorbidities and liver function status. Primary outcome measures include median overall survival using the Kaplan–Meier method and survival rates at 6, 12, 18 and 24 months. Secondary outcomes include clinico-demographic characteristics, treatment regimens (alone or combination) in each line of therapy and real-world progression-free survival. Additionally, prognostic and predictive factors for survival outcomes will be evaluated. Of the planned sample size of 1440 patients, a total of 473 patients with unresectable HCC have been enrolled until August 2022 across 7 countries (Egypt: 105, Hong Kong: 107, India: 79, Russia: 100, Saudi Arabia: 27, Singapore: 50, South Korea: 05). Data collection is currently ongoing and results are expected by 2024. Clinical trial information: NCT05239507 .
A single-arm, open-label, phase II study investigating anti-HER2 ADC plus anti-PD-1 antibody in patients with unresectable locally advanced or metastatic BTC with HER2 overexpression.
Authors: Chen Xiaofeng , Guo Fen , Zhang Xinyi , Qiu Jinrong , Zheng Tongsen , Qiu Hong , Tian Yitong , Pan Lanlan , Zhang Jiaguang , Chen Yizhang , Shen Haoyang , Wang Chao 
Published: January 2023

TPS619 Background: 1. Biliary tract cancer (BTC) accounts for 4% of all digestive tract cancers. In 2016-2020, the incidence of BTC has gradually increased worldwide. In China, gallbladder carcinoma accounted for 1.7% of all tumors and 1.9% of deaths in some regions. 2. The standard second-line treatment regimen is mFOLFOX, with an ORR of 5%, PFS of 2 months and OS of 6.2 months. Methods: This is a single-arm, open-label, phase II study, approximately 31 patients of unresectable locally advanced or metastatic BTC with HER2 overexpression will be enrolled. Each treatment cycle is 14 days. Therapeutic regimen: Disitamab Vedotin 2.5mg/kg IV, D1, Q2W + Zimberelimab 240mg IV, D1, Q2W All patients treated until a loss of clinical benefit or unacceptable toxicity is observed by the investigator. Objective: to evaluate the efficacy and safety of Disitamab Vedotin + Zimberelima in patients with unresectable locally advanced or metastatic BTC with HER2 overexpression Disitamab Vedotin: Vedecitumab is an antibody-drug conjugate (ADC), with a humanized antibody conjugated to four tubulin inhibitor molecules (DAR=4) Zimberelimab: Zimberelimab is a fully human IgG4 monoclonal antibody that specifically binds to PD-1 molecules on the surface of lymphocytes. This drug is approved for r/r cHL and is also effective in the cervical cancer. Clinical trial information: NCT05540483 .