bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1 dose-escalation, dose-expansion trial of intratumoral HER2- and HER3-primed dendritic cells injections for the treatment of early-stage TNBC and HR low positive breast cancer: DecipHER trial.
Authors: Costa Ricardo L , Childress Jennifer A , Abraham Edith , Farrell Carly , Mo Qianxing , Jameel Zena , Soyano Muller Aixa Elena , Lee Kimberley T , Hoover Susan , Kiluk John , Weinfurtner Robert J , Lee Marie Catherine , Laronga Christine , Khakpour Nazanin , Han Hyo S. , Khong Hung T. , Soliman Hatem Hussein , Czerniecki Brian J. 
Published: June 2023

TPS629 Background: Patients with breast cancers (BCs) harboring low expression of hormone receptors (HRs) and human epidermal growth factor receptor-2 (HER2) have poor outcomes. Results from the KEYNOTE-522 trial showed that activation of the immune system using a PD1/PD-L1-targeted approach improves outcomes of patients with these high-risk tumors. Antigen-presenting cells (eg, dendritic cells [DCs]) are pivotal for robust cytotoxic responses due to broader activation of the adaptive immune system (ie, CD4+ and CD8+ Th1) against tumor-associated antigens (ie, HER2 or HER3) expressed by high-risk BCs. Methods: DecipHER is a dose-escalation, dose-expansion phase 1 trial designed to assess the safety and the preliminary efficacy of autologous, HER2- and HER3-primed DCs in combination with KEYNOTE 522 regimen in 30 patients. Patients with clinical stage cT1cN1/2 or cT2-4cN0-2, HR 20, HER2-negative BCs are eligible. Patients with inflammatory BC cancer and uncontrolled immune mediated diseases are excluded. After collection through aphaeresis, autologous DCs will be primed ex vivo against 6 HER2 and 8 HER3 immunogenic peptides. Participants will receive alternating ultrasound-guided intratumoral HER2 and HER3 DC injections administered twice a week for 8 doses in total starting 2 weeks prior to neoadjuvant therapy with KEYNOTE 522 regimen. The dose-escalation phase of the study has 3 planned cohorts (10-20, 30-50, 80-100 million DCs) and follows a 3+3 design (maximum n=18). The 12 additional patients enrolled will be treated at the maximum tolerated dose (MTD) in the dose-expansion cohort. The MTD will be defined as the highest dose level at which < 2 of 6 patients experience dose-limiting toxicities (grade ≥ 3 non-hematologic, ; grade ≥ 3 hematologic toxicity thought be at least possibly related to DCs ; any grade 4 nausea, vomiting, or diarrhea [or grade 3 if duration > 3 days]) during the 5 weeks following treatment initiation with DCs. Secondary endpoints include the absolute risk of adverse events, clinical and pathological responses, and recurrence free survival. Tumor tissue, blood and stool samples will be collected for correlative analyses. The study is open at H. Lee Moffitt Cancer Center. Clinical trial information: NCT05504707 .
A single-arm phase 2 study of peri-operative immune checkpoint inhibition and cryoablation in women with hormone receptor-negative, HER2-negative, early-stage/resectable breast cancer.
Authors: McArthur Heather L. , Comen Elizabeth Anne , Bryce Yolanda , Solomon Stephen Barnett , Leal Jorge Henrique S. , Abaya Christina DiLauro , Martinez Cristal , Basho Reva K , McAndrew Philomena , Larkin Brigid , Page David B. , Mellinger Staci L. , Fredrich Nicole , Moxon Nicole , Reddy Sangeetha M. , Carter Meredith , Patil Sujata , Dogan Basak , Gatti-Mays Margaret Elena , Norton Larry 
Published: June 2023

TPS635 Background: Local tumor destruction with cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. Pre-clinically, cryo with immune checkpoint inhibition (ICI) augmented tumor-specific immune responses and prevented recurrence. Clinically, we established that peri-operative (peri-op) cryo with ICI [ipilimumab (ipi) +/- nivolumab (nivo)] was safe in patients (pts) with operable, early stage breast cancer (ESBC) and generated robust intra-tumoral and systemic immune responses. In this phase 2 study, we evaluate the disease specific impact of peri-op ICI in women with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC), a subset at high risk of early relapse. Methods: Eligible women are ≥18y, with ER <10%, PR <10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. As of 2/14/21, 16/80 pts have been enrolled and treated with ipi/nivo/cryo followed by breast surgery and adjuvant nivo. Pts undergo percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and received ipi (1mg/kg IV) with nivo (240mg IV) 1 to 5 days prior to cryo. After surgery, pts received 3 additional doses of nivo at 240mg IV Q2 weeks. To reflect the US FDA approval of curative-intent pembrolizumab (pembro) in 2021, the protocol was recently amended to allow standard-of-care pembro as an alternative ICI option. Adjuvant capecitabine or olaparib is recommended for all patients per local standard-of-care. Patients will be stratified by NAC platinum administration, NAC anthracycline administration, and clinical nodal status (positive versus negative). The primary endpoint is 3-year Event Free Survival (EFS). Secondary endpoints include Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS), overall survival (OS) and safety. Exploratory correlative studies will be performed on tumor and serum to characterize the immunologic impact of the intervention and to explore predictors of efficacy and toxicity. Clinical trial information: NCT03546686 .
A phase 1, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of HS-10382 (TERN-701) in patients (pts) with chronic myeloid leukemia (CML).
Authors: Li Weiming , Xu Na , Xu Zhongyuan , Zhang Yanli , Li Junmin , Zhu Huanling , Zheng Li , Yan Xiaojing , Du Xin , Wei Hongying , Huang Qiqi , Wei Jiawei , Hu Yu 
Published: June 2023

TPS7081 Background: There is a need for new treatment options for pts with CML who are intolerant/resistant to currently available BCR-ABL1 ATP-binding site targeted tyrosine kinase inhibitors (TKIs). HS-10382 (TERN-701) is a potent, oral small molecule allosteric inhibitor of BCR-ABL. By binding to the myristoyl site of the BCR-ABL1 protein, HS-10382 (TERN-701) locks BCR-ABL1 into an inactive conformation. This results in a mutation-driven resistance profile different from that of ATP-binding site TKIs, providing potential for both monotherapy and combination therapy with ATP-binding site TKIs. In preliminary nonclinical assays, HS-10382 (TERN-701) was highly potent against wild type BCR-ABL1 as well as most common mutations acquired by pts treated with second generation active site TKIs. This ongoing first-in-human phase 1 study is evaluating HS-10382 (TERN-701) in pts with CML. Methods: Eligible adult CML chronic phase (CP) or advanced phase (AP) pts who are resistant or intolerant to prior BCR-ABL-1 TKI therapy are enrolled in an open-label Phase 1 study to evaluate the safety, tolerability, PK and efficacy of HS-10382 (TERN-701). This study is being conducted in two parts: Part 1 dose escalation utilizing a rolling six design and Part 2 dose expansion. In the dose escalation stage, CML-CP/AP pts who are resistant or intolerant to prior BCR-ABL-1 therapy are being enrolled to determine the maximum tolerated dose (MTD) or maximum applicable dose. Doses selected from the escalation part will be evaluated in the expansion stage in CML-CP pts who are resistant or intolerant to prior BCR-ABL-1 TKI therapy and have no T315I mutation. All pts will be carefully followed for adverse events for the duration of study treatment and for 28 days after the last dose of study drug. Pts will be permitted to continue therapy with assessments for progression if the study drug is well-tolerated and the pt has no objective evidence of disease progression. This study is ongoing (enrollment underway for Part 1, dose 3 as of February 2023) with 7 participating study sites in China. Clinical trial information: NCT05367700 .
Phase 1 study to determine the safety and efficacy of onvansertib, a novel, oral, PLK1 inhibitor in patients with proliferative chronic myelomonocytic leukemia relapsed/refractory or intolerant to available therapies.
Authors: McCullough Kristen , Mangaonkar Abhishek A , Burgess Ashya R. , Al-Kali Aref , Alkhateeb Hassan B. , Begna Kebede , Gangat Naseema , Geyer Susan Michelle , Hogan William J. , Litzow Mark Robert , Reichard Kaaren , Saliba Antoine N , Shah Mithun Vinod , Wolanskyj-Spinner Alexandra P. , Patnaik Mrinal Mahesh 
Published: June 2023

TPS7089 Background: Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative overlap neoplasm (MDS/MPN) that can be further divided into MD (WBC < 13 x 109/L) and MP (≥13 x 109/L) subtypes. MP-CMML is enriched in RAS pathway mutations ( NRAS, CBL, KRAS, PTPN11 and NF1), has a shorter median survival (19 vs 36 months), has a higher rate of acute myeloid leukemia (AML) transformation (40% vs 10%) and has a unique transcriptomic and epigenetic composition. These RAS pathway mutations promote selective PLK1 overexpression, a mitotic checkpoint kinase. Given the relative inefficacy of hypomethylating agents (HMA) in MP-CMML and previously demonstrated in vitro and in vivo efficacy data for PLK1 inhibition on MP-CMML with RAS pathway mutations, we designed a phase 1 clinical trial testing the safety of onvansertib, a novel, orally bioavailable, PLK1 inhibitor in relapsed/refractory MP-CMML. Methods: This is an investigator-initiated, prospective, open-label, phase I study of onvansertib in MP-CMML relapsed/refractory (RR) or intolerant to existing therapies including HMA and hydroxyurea. The primary endpoint is characterization of safety. Secondary endpoints include efficacy as defined by the 2015 MDS/MPN International Working Group criteria, volumetric spleen response and symptom response via assessment with MPN-SAF-TSS. Inclusion criteria include MP-CMML RR following hydroxyurea or at least 4-cycles of HMA or intolerance of treatment with either, platelets ≥ 20,000/m3 and Cockcroft-Gault creatinine clearance ≥ 60 mL/min/m2. Hydroxyurea may continue for the first 28 days on study. Onvansertib will be given orally on days 1 through 21 of a 28-day cycle with a Bayesian optimal interval design to assess the safety and recommended phase II dose. Exploratory end points include targeting efficacy, impact of PLK1 and KMT2A expression and interactions with ASXL1 and TET2 mutations. Twenty-five patients will be enrolled at Mayo Clinic in Minnesota, with enrollment open since November 2022. Clinical trial information: NCT05549661 .
BRUIN CLL-314: A phase 3, open-label, randomized study of pirtobrutinib versus ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.
Authors: Woyach Jennifer Ann , Coombs Catherine Callaghan , Lewis Katharine L. , Escalon Maricer P. , Ceccarelli Matteo , Bian Yuanyuan Faith , Wierda William G. 
Published: June 2023

TPS7584 Background: Covalent (c) Bruton tyrosine kinase inhibitors (BTKi) have transformed the management of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but these agents are not curative. cBTKi share pharmacologic liabilities such as low oral bioavailability and a short half-life that may lead to suboptimal BTK target coverage, especially in rapidly proliferating tumors with high BTK protein turnover, such as accelerating CLL/SLL, which can manifest as acquired resistance to cBTKi. Novel therapeutic agents addressing both intolerance and resistance while also improving efficacy are needed. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi, inhibits both wildtype and C481-mutant BTK with equal low nM potency and has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval regardless of intrinsic rate of BTK turnover. In the phase 1/2 BRUIN study, pirtobrutinib demonstrated promising durable overall response rates (ORR) and was well tolerated in patients with CLL/SLL irrespective of prior therapy (including cBTKi), number of prior lines of therapy, BTK C481 mutation status, or reason for prior cBTKi discontinuation. The objective of this study is to compare efficacy and tolerability of pirtobrutinib versus ibrutinib in patients with CLL/SLL. Methods: BRUIN CLL-314 (NCT05254743) is a global, phase 3, open-label, randomized study comparing pirtobrutinib with ibrutinib. Approximately 650 BTKi-naïve patients, either treatment-naïve (up to 30%) or previously treated with other non-BTKi agents, will be randomized 1:1 to receive daily 200 mg pirtobrutinib once daily or 420 mg ibrutinib as continuous monotherapy. Randomization will be stratified by del(17p) status (yes/no) and number of prior lines of therapy (0 vs 1 vs ≥2). Enrollment for this study is ongoing. Adults with CLL/SLL who require therapy per iwCLL 2018 criteria are eligible. Key exclusion criteria include prior exposure to any BTKi, use of some concomitant therapies including anticoagulants, such as warfarin and other vitamin K antagonists, significant cardiovascular disease, active infections, and other clinically significant conditions. The primary objective is to establish non-inferiority of pirtobrutinib versus ibrutinib by comparing the ORR per iwCLL guidelines assessed by an independent review committee. Superiority of pirtobrutinib versus ibrutinib in progression-free survival is a key secondary outcome. Other endpoints include duration of response, overall survival, time-to-next treatment, tolerability, and patient-reported outcomes. Trial efficacy and safety will be monitored by an independent data monitoring committee. Clinical trial information: NCT05254743 .
MajesTEC-9: A randomized phase 3 study of teclistamab versus pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma.
Authors: Touzeau Cyrille , Hungria Vania TM , Bhutani Divaya , Landgren Ola , Vieyra Diego , Guo Yue , Verona Raluca , Miao Xin , Qi Mia , Watkins Latisha , Shah Priya , Chastain Katherine , Qi Ming , Quach Hang 
Published: June 2023

TPS8067 Background: Despite the advance in therapeutic options for patients with relapsed/refractory multiple myeloma (RRMM) over recent years, there remains a significant unmet medical need for new, well-tolerated therapies in earlier lines for patients who have previously received an anti-CD38 monoclonal antibody and lenalidomide. Teclistamab is the first B-cell maturation antigen (BCMA)-directed bispecific antibody approved for the treatment of triple class-exposed RRMM. Teclistamab redirects CD3+ T cells to mediate T-cell activation and subsequent lysis of BCMA-expressing myeloma cells. MajesTEC-9 (NCT05572515) is a phase 3, randomized, open-label, multicenter study comparing teclistamab with investigator’s choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in patients with RRMM. Methods: Patients aged ≥18 years with RRMM (International Myeloma Working Group [IMWG] criteria) must have evidence of progressive disease or failure to achieve a response to last line of therapy and an Eastern Cooperative Oncology Group performance status score of 0–2. All patients must have received 1–3 prior lines of therapy, including ≥2 consecutive cycles of an anti-CD38 monoclonal antibody and ≥2 consecutive cycles of lenalidomide. Those treated with prior BCMA-directed therapy will be excluded. Approximately 590 patients will be randomized 1:1 to receive either teclistamab (28-day cycles) or PVd (21-day cycles) or Kd (28-day cycles). Stratification factors include investigator’s choice of PVd or Kd, stage of disease, number of prior lines of therapy, and anti-CD38 monoclonal antibody refractory status. Treatment will continue until disease progression, death, intolerance, withdrawal of consent, or end of study, whichever occurs first. The primary endpoint is progression-free survival (IMWG 2016 criteria); secondary endpoints include overall response rate, duration of response, and overall survival. Adverse events (AEs) will be graded by Common Terminology Criteria for AEs v5.0; cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome will be graded by American Society for Transplantation and Cellular Therapy criteria. The study opened in January 2023 and enrollment is ongoing. Clinical trial information: NCT05572515 .
A phase I-III platform study evaluating the safety and efficacy of multiple therapies in patients with biomarker-defined locally advanced, unresectable stage III non–small-cell lung cancer (NSCLC).
Authors: Paz-Ares Luis G. , Gay Carl Michael , Zhou Caicun , Kato Terufumi , Corrales Luis , Redhead Karl , Rahman Ahmadur , Bradley Denise , Theogaraj Elizabeth , Hutchinson Katherine E. , Shagan Sarah M. , Solomon Benjamin J. 
Published: June 2023

TPS8605 Background: Durvalumab following chemoradiation (CRT) is a standard of care for unresectable stage III NSCLC, but there remains an unmet need for improved therapeutic options among patients with driver-mutated tumors that are unresponsive to immunotherapy. As targeting of specific driver mutations (e.g. ALK, RET, ROS1) has proven effective in the metastatic setting, it is hypothesized that outcomes could also be improved for patients with driver-mutated stage III NSCLC. Methods: BO42777 (NCT05170204) is a phase I–III platform study evaluating the safety and efficacy of multiple targeted therapies versus durvalumab following CRT in patients with locally advanced, unresectable stage III NSCLC. Biomarker eligibility is determined via local tissue testing or central testing within the BX43361 master screening study (NCT05419375). Biomarker-eligible patients are enrolled into the relevant cohort and randomized 1:1 to receive durvalumab or targeted therapy (alectinib [ ALK+], entrectinib [ ROS1+], or pralsetinib [ RET fusion+]). New cohorts may be added in the future. Key inclusion criteria: locally advanced, unresectable stage III NSCLC, age ≥18 years, ≥2 prior cycles of concurrent or sequential CRT (cCRT or sCRT), and ECOG PS 0–2. Patients are stratified based on staging (IIIA vs IIIB or IIIC), CRT type (cCRT vs sCRT), and PD-L1 status (tumor cell score < 1% vs ≥1% vs unknown) and will receive investigational treatment for three years or durvalumab for one year, until progression or maximum duration of treatment, unacceptable toxicity, consent withdrawal, or death. Primary endpoint: progression-free survival (RECIST v1.1) by blinded independent central review. Key secondary endpoints: distant metastasis-free survival, time to CNS progression, objective response rate, duration of response, overall survival, and safety (adverse events). Time to confirmed deterioration and patient-reported outcomes will be assessed through questionnaires. Tumor response will be assessed by CT/MRI imaging at regular intervals. Enrolment is ongoing (target of 320 patients) across 200 sites in 11 countries. As of 7 February 2023, five patients have been randomized. This trial in progress was previously presented at ELCC, Luis Paz-Ares et al. (#744), and reused with permission. Clinical trial information: NCT05170204 .
A randomized, double blinded, multicenter phase 3 study of platinum-based chemotherapy with or without QL1706 as adjuvant therapy in completely resected stage II-IIIb NSCLC.
Authors: Zhu Yuming , Jiang Tao , Fang Lianghua , Zhang Tao , Kang Xiaoyan , Zhou Caicun 
Published: June 2023

TPS8606 Background: Adjuvant atezolizumab is approved for PD-L1 positive stage II-IIIA NSCLC in USA and China. To date, there are few clinical studies on dual immune checkpoint inhibitors in adjuvant settings of NSCLC. QL1706, a MabPair product, is a novel bifunctional antibody containing a mixture of anti-PD-1 IgG4 and anti-CTLA-4 IgG1 antibodies. QL1706 monotherapy has demonstrated good safety and promising antitumor activity in advanced solid tumors in a phase Ia/Ib study with 518 patients, including 146 NSCLC patients. Meanwhile, in NSCLC patients with negative oncogene drivers, QL1706 plus 2 cycles of chemotherapy as first line treatment resulted in an ORR of 58.6% (17/29) and the mPFS was 6.97 months. Furthermore, in the EGFR mutant NSCLC patients who previously were treated with EGFR-TKI, QL1706 plus platinum-based chemotherapy and bevacizumab showed promising efficacy with an ORR of 64.5% (20/31). This study is designed to investigate the efficacy and safety of QL1706 or placebo plus platinum doublet chemotherapy as adjuvant treatment in stage II-IIIB NSCLC. Methods: In this phase Ⅲ, randomized, double-blind, placebo-controlled, multicenter study, 632 eligible pts, who is completely resected stage Ⅱ-ⅢB NSCLC (AJCC 8th) with negative EGFR, ALK etc, will be enrolled. Pts will be randomized 1:1 to receive QL1706 (5 mg/kg) or placebo plus chemotherapy, administered every 3 weeks (Q3W). The regimen of vinorelbine/paclitaxel plus cisplatin/carboplatin is chosen for squamous NSCLC, while pemetrexed/vinorelbine plus cisplatin/carboplatin for non-squamous NSCLC. Randomization will be stratified by PD-L1 TPS (ie, < 1%, ≥1%), disease stage (stage II, III) and predominant tumor histology (ie, squamous vs non-squamous). The primary endpoint is disease-free survival (DFS) per investigators in PD-L1 TPS ≥1% pts and in all randomized pts, which will be tested hierarchically. An interim analysis is to occur when about 70% DFS events achieved in pts with PD-L1≥1%. Enrollment began in Nov, 2022. ClinicalTrials.gov NCT05487391. Clinical trial information: NCT05487391 .