bluuebunny/crossref_metadata_2025_split huggingface dataset:
STELLAR-303: A phase 3 study of XL092 in combination with atezolizumab versus regorafenib in patients with previously treated metastatic colorectal cancer (mCRC).
Authors: Hecht J. Randolph , Tabernero Josep , Parikh Aparna Raj , Wang Yijia , Wang Zhong , Schwickart Martin , Curran Dominic , Saeed Anwaar 
Published: January 2023

TPS267 Background: The prognosis of patients with mCRC is poor, with a 5-year survival rate of 14% (American Cancer Society 2020). Patients who have progressed after front-line chemotherapy have limited treatment options. Regorafenib or trifluridine-tipiracil are approved for patients in the third- or later-line setting, but survival benefit is limited. While immune checkpoint inhibitor (ICI) therapy is approved (nivolumab ± ipilimumab, and pembrolizumab) in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mCRC, the MSI-H phenotype is limited to ~5% of mCRC patients. In phase 1/2 trials, ICIs in combination with VEGFR2 multi-kinase inhibitors (MKIs) have demonstrated encouraging clinical activity in mCRC, including atezolizumab and durvalumab (ICIs) in combination with the MKI cabozantinib, with data suggesting a greater benefit in RAS wild-type (wt) vs mutant (mut) disease (Abrams TA, et al. ASCO GI 2022:Abs 121; Saeed A, et al. ASCO GI 2022:Abs 135). XL092 is a novel MKI, targeting MET, VEGFR2, and the TAM kinases AXL and MER; the relatively short half-life (~21 hours) of XL092 is favorable for once-daily (QD) dosing and dose modification to manage tolerability. STELLAR-303 is a phase 3 study evaluating the efficacy and safety of XL092 + atezolizumab versus regorafenib in patients with previously treated RASwt or RASmut mCRC. Methods: STELLAR-303 (XL092-303; NCT05425940) is a global, open-label, randomized phase 3 study. Eligible patients are ≥18 years old and have mCRC that is measurable per RECIST v1.1, are documented not to have MSI-H or dMMR disease, and have an ECOG performance status of 0–1 and adequate organ function. RAS and MSI/dMMR status must be determined by a tissue-based analysis. Patients must have progressed during/after or be intolerant to standard-of-care treatments for mCRC; prior regorafenib, trifluridine/tipiracil, or PD-L1/PD-1 ICIs are not allowed. Patients are randomized 1:1 to XL092 100 mg PO QD + atezolizumab 1200 mg IV Q3W or to regorafenib 160 mg PO QD (21 days of 28-day cycle); randomization is stratified by geographic region (Asia vs other), RAS status (wt vs mut), and liver metastases (yes/no). The study plans to enroll 600 patients (400 RASwt and 200 RASmut). The primary endpoint is overall survival in the RASwt population, with additional efficacy endpoints of progression-free survival, objective response rate, and duration of response per RECIST v1.1 by investigator; efficacy endpoints will also be assessed in the overall study population and in patients with RASmut mCRC. Additional endpoints will assess safety, quality of life, changes in biomarkers, pharmacokinetics, immunogenicity of atezolizumab, and healthcare utilization. Enrollment is ongoing. Clinical trial information: NCT05425940 .
SEAMARK: Randomized phase 2 study of pembrolizumab + encorafenib + cetuximab vs pembrolizumab alone for first-line treatment of BRAF V600E–mutant microsatellite instability–high (MSI-H)/mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC).
Authors: Kopetz Scott , Bekaii-Saab Tanios S. , Yoshino Takayuki , Chung Chin-Hee , Zhang Xiaosong , Tabernero Josep 
Published: January 2023

TPS268 Background: Among patients with MSI-H/dMMR CRC, BRAF mutations occur in approximately 30%. MSI-H/dMMR and BRAF mutations are both associated with poor prognosis; in patients who have both biomarkers, poor prognosis is thought to be driven by the BRAF mutation. Pembrolizumab is indicated for the treatment of patients with MSI-H/dMMR unresectable or metastatic CRC (mCRC). The BRAF inhibitor encorafenib, in combination with cetuximab, an anti-EGFR antibody, is indicated for previously treated patients with BRAF V600E-mutant mCRC. Currently, there are no first-line treatment options indicated specifically for patients with both MSI-H/dMMR and BRAF V600E-mutant mCRC. To assess the safety and efficacy of combining pembrolizumab with encorafenib + cetuximab, the SEAMARK study will evaluate this combination vs pembrolizumab alone in patients with previously untreated BRAF V600E-mutant MSI-H/dMMR mCRC. Methods: SEAMARK (NCT05217446) is an open-label, multicenter, randomized, phase 2 study. Approximately 104 patients (randomized 1:1; stratified by Eastern Cooperative Oncology Group Performance Status [ECOG PS] 0 vs 1) will receive either pembrolizumab + encorafenib + cetuximab or pembrolizumab. Enrolled patients must be aged ≥16 or ≥18 years (per country-specific regulations) and have previously untreated BRAF V600E-mutant MSI-H/dMMR mCRC; measurable disease (Response Evaluation Criteria in Solid Tumors 1.1); ECOG PS 0 or 1; and adequate bone marrow, hepatic, and renal function. Patients who received prior treatment with BRAF/EGFR inhibitors or immune checkpoint inhibitors, or who have brain metastases (unless radiologically stable) or RAS mutation (or unknown RAS status), will be excluded. The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include safety and tolerability, overall survival, objective response rate, duration of response, and quality of life. Enrollment started in July 2022. Clinical trial information: NCT05217446 .
Durvalumab (MEDI 4736) with extended neoadjuvant regimens in rectal cancer: A randomised phase II trial (PRIME-RT).
Authors: Roxburgh Campbell SD , Hanna Catherine Ruth , Graham Janet , Saunders Mark P. , Samuel Leslie M. , MacLeod Nicholas James , Devlin Lynsey , Edwards Joanne , Hillson Lily , McMahon Ross K , Jones Leia Ashleigh , Kelly Caroline , Lewsley Liz-Anne , Morrison Paula , Atherton Peter , Walker Nicola , Gourlay Jacqueline , Tiplady Ellie , Adams Richard , O'Cathail Sean Michael 
Published: January 2023

TPS282 Background: Advances in multi-modality treatment of locally advanced rectal cancer (LARC) have resulted in low local recurrence rates, but many patients still die from distant disease. There is increasing recognition that with neoadjuvant treatment some patients achieve a complete response and may avoid surgical resection. PRIME-RT tests the inclusion of neoadjuvant immunotherapy with the aim of enhancing complete response rates, improving stoma-free survival and reducing distant relapse. Methods: PRIME-RT is a multi-centre, open label, phase II, randomised trial for patients with newly diagnosed LARC. Eligible patients are randomised to Arm A: short course radiotherapy (25 Gray in 5 fractions) with concomitant durvalumab, followed by durvalumab and FOLFOX chemotherapy, or Arm B: long course chemoradiotherapy (50 Gray to primary tumour, 45 Gray to elective nodes, in 25 fractions with capecitabine) with concomitant durvalumab followed by FOLFOX and durvalumab. The primary endpoint is complete response rate in each arm. Bio-specimens including serial tumour biopsies and peripheral blood samples are collected prior to, during, and following treatment to explore the molecular and immunological factors underpinning treatment response. The main trial will recruit up to 42 patients and commence after a safety run-in which is recruiting patients with metastatic disease. After opening in January 2021, the four patients completed the safety run in and the main trial commenced in March 2022. The trial is currently open across 5 UK sites. Up to date recruitment details will be provided at the time of presentation but at the time of writing this is ahead of target. Early recruitment to PRIME-RT has shown that adding immunotherapy in the neoadjuvant setting for LARC is feasible. Furthermore, on treatment biospecimen collection is also feasible across multiple sites. The expectation is that the trial will provide efficacy and safety information which allows the optimal treatment approach to be tested within a larger phase clinical trial. Core funding (Glasgow CRUK CTU) and trial-specific funding (Astrazeneca). Clinical trial: NCT04621370; ISRCTN18138369. Clinical trial information: ISRCTN18138369 .
Trial in progress: A phase II, multicenter, open-label study of PolyPEPI1018 in combination with atezolizumab in participants with relapsed or refractory microsatellite-stable metastatic colorectal (MSS mCRC) cancer (Oberto-301).
Authors: Hubbard Joleen M. , Ahn Daniel H. , Jones Jeremy Clifton , Wittenberger Kathleen , Molnar Levente , Lorincz Orsolya , Somogyi Eszter , Csiszovszki Zsolt , Youssoufian Hagop , Toke Eniko Rita 
Published: January 2023

TPS283 Background: Colorectal cancer (CRC) is among the top three most commonly occurring cancers globally. CRC is now routinely classified as MSI-high (MSI-H) or microsatellite-stable (MSS) based on the detection or absence of molecular markers of genetic instability, respectively. The efficacy of checkpoint inhibitor immunotherapy in MSI-H CRC has not been replicated in MSS CRC. Therefore, additional interventions are needed to convert immunologically “cold” MSS CRC to “hot” tumors resembling MSI-H tumors. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine containing 12 immunogenic epitopes derived from 7 cancer testis antigens (CTAs) frequently expressed in patients with CRC. PolyPEPI1018 successfully restored and boosted pre-existing anticancer immunity of MSS mCRC subjects and triggered recruitment and infiltration of cytotoxic T cells into the tumor. In first line metastatic MSS CRC, PolyPEPI1018 in combination with fluoropyrimidine/bevacizumab vaccine was safe and demonstrated early evidence of clinical activity. Therefore, we hypothesized that the combination of PolyPEPI1018 and atezolizumab will convert a “cold” MSS mCRC to a “hot” tumor and may increase the likelihood of inducing favorable antitumor immunity and subsequent clinical benefit. Methods: The study is a phase 2, multicenter, single-arm clinical trial of PolyPEPI1018 vaccine (1.2 mg, sc, every 3 weeks) and atezolizumab (1200 mg, iv, every 3 weeks) for patients with advanced or metastatic MSS CRC who have progressed on 2 or 3 lines of prior standard regimens. 28 patients will be enrolled at 3 US sites with a primary objective to assess the safety and tolerability of multiple doses of PolyPEPI1018 in combination with atezolizumab. Secondary endpoints include objective response rate (ORR) assessed by RECIST v1.1, vaccine induced immunological response rate (IRR), progression-free survival and overall survival. Correlative aims include assessing blood and tissue biomarkers (PD-L1, Immunoscore®IC, ctDNA, clinical tumor markers) for association with clinical benefit. An exploratory study is being conducted for co-development of a companion diagnostic based on HLA-genotype and computational personal epitope (PEPI) prediction test. A Simon 2-stage design will be used for the initial assessment of ORR. If pre-specified activity goal for the first stage of accrual (n = 18) is met, additional 10 participants will be enrolled to the second stage. A formal review of safety will be performed after the initial 6 participants have received at least 2 cycles of study therapy. The study is open with 10 patients enrolled at time of submission. Clinical trial information: NCT05243862 .
TST001 (a high affinity humanized anti-claudin18.2 monoclonal antibody) in combination with nivolumab plus capecitabine and oxaliplatin as first-line or with nivolumab as late-line treatment in locally advanced and metastatic gastric/gastroesophageal junction (G/GEJ) cancer: Design of cohorts from a phase I/IIa study (TST001-1002).
Authors: Guo Weijian , Germa Caroline , Qi Chuan , Qian Chunhua , Yao Jenny , Wang Jianming , Zhang Lijuan , Qian Xueming , Xia Zhenzhong 
Published: January 2023

TPS476 Background: TST001 (osemitamab) is a high affinity recombinant humanized ADCC enhanced antibody that can specifically bind to the extracellular structure of claudin 18.2 protein and eliminate cancer cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Pre-clinical studies have shown that TST001 has potent single agent anti-tumor activity and synergistic effect when used in combination with immune checkpoint inhibitors in claudin 18.2 positive tumors. In the ongoing phase I/IIa clinical trial (NCT04495296), TST001 alone or in combination with capecitabine and oxaliplatin (CAPOX) in the treatment of G/GEJ adenocarcinoma has revealed encouraging preliminary efficacy (IGCC 2022, ESMO 2022). The combination of TST001 with nivolumab (in 2nd/3rd line treatment) or nivolumab + standard of care chemotherapy (in 1st line) are being explored in the same study. Methods: Each cohort includes a dose escalation phase in CLDN18.2 non-selected patients and a dose expansion phase in CLDN18.2 positive patients, aiming to identify the recommended Phase 2 dose and evaluate the safety, tolerability and preliminary efficacy of TST001 in combination with nivolumab plus CAPOX or nivolumab in patients with G/GEJ adenocarcinoma. First line, treatment naïve patients with HER2 negative or unknown, locally advanced or metastatic G/GEJ adenocarcinoma will receive 21 days cycles of TST001 combined with CAPOX plus nivolumab until disease progression or unacceptable toxicity, with oxaliplatin for a maximum of 8 cycles and capecitabine per investigator’s discretion after that; 2nd or 3rd line patients with locally advanced or metastatic G/GEJ adenocarcinoma will receive 21 days cycles of TST001 combined with nivolumab. AEs will be categorized by CTCAE v5.0. Efficacy will be evaluated every 6 weeks per RECIST1.1. These two cohorts will be initiated in September 2022 from about 40 sites in China. Combinations with nivolumab are being explored in the US study too (NCT04396821). Clinical trial information: NCT04495296 .
Combined intraperitoneal and systemic chemotherapy as adjuvant or perioperative chemotherapy for patients with type 4 scirrhous gastric cancer: PHOENIX-GC2 trial.
Authors: Ishigami Hironori , Omori Takeshi , Tsuji Yasushi , Shinohara Hisashi , Yabusaki Hiroshi , Kobayashi Daisuke , Takahari Daisuke , Hata Hiroaki , Kusumoto Tetsuya , Kanda Mitsuro , Oba Koji , Kitayama Joji , Seto Yasuyuki ,   Japan Intraperitoneal Chemotherapy Study Group
Published: January 2023

TPS477 Background: Despite recent progress in adjuvant and perioperative chemotherapy, the prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combination chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a multicenter, open-label, randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Methods: Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled from 40 hospitals throughout Japan. Clinical trial information: jRCT2031200087 .
Single-arm phase II trial to evaluate the safety of laparoscopic/robotic total gastrectomy with spleen-preserving splenic hilar dissection for locally advanced proximal gastric cancer that invades the greater curvature: JCOG1809.
Authors: Kinoshita Takahiro , Yoshikawa Takaki , Ojima Toshiyasu , Omori Takeshi , Cho Haruhiko , Honda Michitaka , Nunobe Souya , Kurokawa Yukinori , Kuroda Shinji , Mizusawa Junki , Fukuda Haruhiko , Boku Narikazu , Terashima Masanori 
Published: January 2023

TPS479 Background: The standard treatment for locally advanced proximal gastric cancer invading the greater curvature is “open total gastrectomy combined with splenectomy” (OTG+S) aiming for whole clearance of the splenic hilar lymph nodes. However, its pertinent postoperative severe complication (e.g. pancreatic fistula) is problematic. An objective of this study is to evaluate the safety of “laparoscopic or robotic total gastrectomy with spleen-preserving splenic hilar dissection” (LRSHD) as a new treatment option which has a potential to reduce surgical morbidity, subsequently to replace the current standard treatment, OTG+S. Methods: This is a multicenter single-arm phase II trial. The main eligibility criteria are as follows; clinical T2-4a resectable locally advanced proximal gastric adenocarcinoma that invades the greater curvature; without obvious lymph node metastasis at the splenic hilum nor direct invasion to the spleen/splenogastric ligament. Protocol treatment is laparoscopic or robotic total gastrectomy with splenic hilar lymph node dissection (D2 + No.10 lymphadenectomy according to the Japanese guidelines) in which the spleen is preserved with skeletonizing the splenic vessels. Quality control of surgery is assured by surgeon’s qualification and central peer review of intraoperative photo at the splenic hilum after dissection. The primary endpoint is the proportion of postoperative pancreatic fistula and/or intra-abdominal abscess formation with Clavien-Dindo Grade III or higher (within 30 days after surgery). Secondary endpoints are intraoperative blood loss, operation time, mortality, overall postoperative complication, number of yield splenic hilar nodes, number of metastatic splenic hilar nodes, conversion to splenectomy, conversion to laparotomy, relapse-free survival, and overall survival. Sample size was set as 85 patients to obtain 80% power considering that 15% of patients are judged as unresectable intraoperatively, with the hypothesis that the primary endpoint would have an expected value of 7% and a threshold value of 16% in one-sided alpha of 0.1. Planned accrual period is 5 years. The accrual began in August 2019. As of August 2022, 53 of the planned 85 patients (62.4%) have been enrolled. When the safety of LRSHD is proved by this study, a non-inferiority phase III trial will be consequently launched. Clinical trial registry number: UMIN000037580. Clinical trial information: UMIN000037580 .
A phase II study to evaluate anlotinib plus TQB2450 as adjuvant therapy in patients with esophageal squamous cell carcinoma (ALTER-E005).
Authors: Guo Changying , Chen Shengjia , Ye Yongqiang , Mao Wei-Min 
Published: January 2023

TPS488 Background: About 30.3-58.0% of patients who undergo esophagectomy may experience recurrence. The efficacy of postoperative chemoradiation has not been demonstrated in a randomized trial in patients with esophageal squamous cell carcinoma (ESCC) compared to surgery along. Therefore, it is urgent to explore more effective and safer postoperative regimen for resectable ESCC. Checkmate 577 has demonstrated immunotherapy can prolong disease free survival (DFS) for patients who have residual disease following preoperative chemoradiation and R0 resection. Anlotinib is an orally administered tyrosine kinase inhibitor that targets VEGFR1-3, FGFR1-4 and PDGFRα/β. In a randomized, double-blind phase 2 trial, the use of anlotinib in previously treated metastatic ESCC patients significantly improved progression-free survival (PFS) compared with placebo ( NCT02649361 ). TQB2450 is a novel humanized monoclonal antibody against PD-L1, which has shown encouraging activity in combination with anlotinib in the treatment of multiple tumors, such as biliary tract cancer (NCT03996408) and ovarian cancer (NCT04236362). The ALTER-E005 study is designed to evaluate the efficacy and safety of anlotinib combined with TQB2450as adjuvant therapy in ESCC patients. Methods: ALTER-E005 is a multi-center, single-arm, phase II study. A total of 30 patients will be enrolled. Eligible pts (≥18 years) must be histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC; received radical (R0) resection of ESCC with no recurrence in imaging examination within 6-12 weeks after surgery; ECOG PS 0–1. Patients enrolled will receive oral anlotinib 12 mg on days 1-14 and intravenous TQB2450 1,200 mg on day 1 every 3 weeks until disease recurrence. The primary endpoint is DFS. The secondary endpoints include safety, 1-year DFS rate, 3-year DFS rate, 1-year overall survival (OS) rate, and 3-year OS rate. Enrollment to the ALTER-E005 trial is currently ongoing in China. Clinical trial information: NCT05252078 .
Phase 1/2 trial of vesicular stomatitis virus expressing human interferon-β and NIS (VSV-IFNβ-NIS), with pembrolizumab, in patients with neuroendocrine carcinoma.
Authors: McGarrah Patrick Walsh , Naik Shruthi , Halfdanarson Thorvardur Ragnar , Leventakos Konstantinos , Peng Kah Whye , Russell Stephen J. , Adjei Alex A. , Molina Julian R. 
Published: January 2023

TPS657 Background: Poorly differentiated neuroendocrine carcinoma (NEC) is an aggressive malignancy comprising both pulmonary and extrapulmonary primary sites. NEC includes both small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), as well as other neuroendocrine carcinomas arising from any primary organ. A substantial portion (~40%) of NEC arises from gastrointestinal primary sites. The optimal systemic therapy beyond first line platinum and etoposide is not established. There is a critical need to improve upon the median survival in the second line, as most patients do not survive more than 6 months. The efficacy of single agent immune checkpoint inhibitors (ICIs) in NEC has been disappointing. One possible explanation for this is that the tumor microenvironment in NEC is non-inflamed. VSV-IFNβ-NIS is a vesicular stomatitis virus (VSV)-based oncolytic virus being tested in multiple early phase clinical trials. Preliminary studies of immune responses in patients receiving VSV-IFNβ-NIS therapy suggest some patients develop T cell responses to viral antigens and known tumor antigens. We hypothesize that VSV-IFNβ-NIS therapy may convert a non-inflamed or immune-excluded phenotype in NEC to a highly inflamed phenotype that sensitizes the tumor to ICIs. Methods: This is a phase 1-2 safety run-in study designed to determine the safety of VSV-IFNβ-NIS in combination with a single agent ICI, pembrolizumab, followed by dose expansion in patients with refractory non-small cell lung cancer (NSCLC) or NEC. The safety run-in portion of this study has been completed, and we are presently testing the recommended phase 2 dose (RP2D) of VSV-IFNβ-NIS in an expansion cohort of patients with SCLC or NEC of any primary site. Patients must have previously progressed on at least one line of systemic therapy. Prior treatment with checkpoint inhibitors is permitted. Patients are treated one time with the RP2D of 1.0x10^11 TCID50 VSV-IFNβ-NIS on day 1, followed by pembrolizumab on day 8 and then pembrolizumab every 21 days until progression, up to 2 years. The primary objective is to estimate the response rate by RECIST 1.1. Secondary objectives include estimation of disease-control rate, duration or response, progression-free survival, overall survival, and safety signals. The NEC expansion cohort will seek to enroll 10 patients. If at least one objective response is observed, and safety is confirmed, the regimen will be considered for future study. Clinical trial information: NCT03647163 .