bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1b study to evaluate the efficacy, safety, and pharmacokinetics of an investigational microbiome therapeutic, SER-155, in adults undergoing hematopoietic stem cell transplantation.
Authors: Ponce Doris M. , Kosuri Satyajit , Khera Nandita , DeFilipp Zachariah Michael , Lombardo Mary-Jane , Ford Christopher B. , Peled Jonathan U. , Van Den Brink Marcel R. M. , von Moltke Lisa , Tejura Bindu 
Published: June 2023

TPS7080 Background: In patients undergoing allogeneic hematopoietic cell transplantation (HCT), loss of gastrointestinal microbial diversity is associated with risk of bloodstream infections (BSI), acute graft-versus-host disease (aGvHD), and death. SER-155 is a rationally designed investigational cultivated microbiome therapeutic, hypothesized to improve clinical outcomes in HCT by restoring colonization resistance to potential pathogens, promoting epithelial barrier integrity, and reducing colonic inflammation. SER-155-001 is a Phase 1b study evaluating the efficacy, safety, and pharmacokinetics (PK) of SER-155 in adults undergoing HCT. Methods: This study will enroll approximately 70 subjects ≥18 years in an open-label Cohort 1 (n = 10) followed by a double-blind, placebo-controlled Cohort 2 (n = 60) randomized 1:1 to SER-155 or placebo. A variety of conditioning regimens, donor types, and GVHD-prophylaxis regimens are included. Exclusion criteria include history of severe colitis or active inflammatory bowel disease or total colectomy, umbilical cord blood or ex vivo T-cell depletion, exposure to fecal microbiota transplant or any live microbial therapeutic within 3 months prior to screening, and evidence of relapse or progression of hematologic malignancy (minimal residual disease is allowed). Following screening, participants in both cohorts receive 2 treatment courses (one before and one after HCT), each comprised of microbiome conditioning with oral vancomycin or placebo followed by SER-155 or placebo, plus a conditional 3rd treatment course if the subject receives antibiotics. Safety outcomes are followed through 52 weeks post HCT. The primary endpoint is the incidence and severity of adverse events, serious adverse events, and adverse events of special interest. Secondary endpoints include rates of BSI, gastrointestinal infections, aGvHD, febrile neutropenia and overall survival. Microbiome related endpoints include engraftment of SER-155 bacterial strains in the gastrointestinal tract (PK endpoint) and fecal microbiome diversity, composition and metabolites. Results: Cohort 1 enrollment is complete, with 13 participants receiving SER-155. In December 2022, the Data and Safety Monitoring Committee supported continuation to Cohort 2 enrollment following review of safety data from Cohort 1. Enrollment in Cohort 2 is underway. Conclusions: This Phase 1b study is designed to assess the safety, and clinical efficacy of SER-155 in allogeneic HCT, expanding the clinical experience of microbiome- directed interventions in allogeneic HCT recipients. Clinical trial information: NCT04995653 .
EXCEED-ET: A single-arm multicenter study to assess the efficacy, safety, and tolerability of ropeginterferon alfa-2b-njft (P1101) in North American adults with essential thrombocythemia.
Authors: Masarova Lucia , Mascarenhas John , Qin Albert , Shih Weichung , Sato Toshiaki , Urbanski Raymond , Zagrijtschuk Oleh , Zimmerman Craig 
Published: June 2023

TPS7088 Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) characterized by a high platelet count due to an overacting JAK-STAT pathway as a result of the most common mutations in JAK2, CALR and MPL genes. There is a high, unmet clinical need for safe and effective treatment options for patients with ET who require cytoreduction, both naïve and previously exposed to hydroxyurea (HU) or anagrelide (ANA). In addition to blood count control and thrombohemorrhagic risk reduction, treatment for ET should also halt/prevent disease progression to post-ET myelofibrosis. Reduction in variant allele frequency and changes in marrow morphology may lead to the elimination of the malignant clone, and treatment with an interferon may achieve this outcome. Interferons have been used in the treatment of MPNs for over 30 years with well-established improvements in hematological and molecular rates, but interferons are not approved by a regulatory agency for the treatment of ET. The objective of this study is to assess the efficacy of ropeginterferon alfa-2b-njft, a new generation interferon alfa, in adults with ET who live in the US or Canada. Methods: This single-arm, open-label study includes a 28-day screening period, a 12-month treatment phase, and a 28-day follow-up period, for a total trial duration of 14 months. An extension phase will supply ropeginterferon alfa-2b-njft to patients deriving benefit for a total of 3 years of treatment. Adults diagnosed with ET according to the WHO 2016 criteria with a platelet count at screening > 450 x 109/L, cytoreductive treatment naïve, or with prior use or currently on HU and/or ANA may participate. Prior treatment with an interferon is an exclusion factor. Patients with a history or presence of clinically relevant depression, risk of suicide, or autoimmune disease may not participate. Ropeginterferon alfa-2b-njft will be administered subcutaneously every 2 weeks at the starting dose of 250 mcg (Week 0), 350 mcg (Week 2), and target dose of 500 mcg (Week 4) and remain fixed for the 12-month treatment period. Subjects currently on HU or ANA will follow a pre-specified dose-tapering schedule. All subjects will receive low-dose aspirin unless contraindicated. The primary endpoint is a durable response defined as the proportion of subjects who achieve simultaneous peripheral blood count remission (platelets ≤400 x109/L and WBC < 10 x 109/L) for at least 80% of bi-weekly measurements consecutively between weeks 32-52, a durable resolution of disease-related symptoms according to the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), and absence of bleeding or thrombotic events. This study is being sponsored by PharmaEssentia USA. Clinical trial information: NCT05482971 .
The ELiPSE-1 study: A phase 1, multicenter, open-label study of CNTY-101 in subjects with relapsed or refractory CD19-positive B-cell malignancies.
Authors: Patel Krish , Rothman Sarah , Das Poulomee A , Yee Stephanie , Ramachandran Indu , Koumenis Iphigenia , Cook Terry A , Yuan Ying , Trede Nikolaus S. , Mattour Ahmad Hatem 
Published: June 2023

TPS7580 Background: Century Therapeutics’ foundational technology is built on induced pluripotent stem cells, differentiated from allogeneic approaches that utilize non-renewable donor-derived cells. This approach allows production of a clonal cell bank of precisely edited cells that can be expanded and differentiated to supply large amounts of homogeneous allogeneic therapeutic products for off-the-shelf use. CNTY-101 is an allogeneic Chimeric Antigen Receptor NK (CAR-NK) cell product with genetic modifications designed to specifically target CD19-expressing B-cell malignancies, reduce allorejection in the recipient allowing for repeat dosing, increase persistence, and enable cell elimination in the event of unexpected adverse events. CNTY-101, as a CAR-NK product, has the potential for improved safety over T-cell based cellular therapies. Methods: This first-in-human study will determine the MTD and recommended Phase 2 regimen (RP2R) of CNTY-101 in combination with subcutaneous (SC) IL-2 in patients with R/R aggressive and indolent CD19-positive B-cell Non-Hodgkin lymphomas including diffuse large B-cell lymphoma, mantle cell lymphoma, primary mediastinal large B-cell lymphoma, follicular lymphoma and marginal zone lymphoma, who are without other treatment options. Part 1 of the study (dose escalation using the BOIN design) will start with a dose of CNTY-101 cells without IL-2 (1 to 3 subjects), followed by dose escalation up to four dose cohorts administering a single dose of CNTY-101 cells in combination with IL-2 daily for 8 days (Sched A). After the single-dose MTD (or the maximal single dose) has been reached, a fractionated schedule of 3 doses per 28-day cycle, administered on Days 1, 8, and 15 (Sched B), will also be explored, starting with approximately one-third the maximum single dose level of CNTY-101, followed by escalation/de-escalation. Subjects in whom CNTY-101 shows signs of clinical benefit (i.e. stable disease or better per Lugano 2014 criteria) may receive additional cycles of CNTY-101 if the Investigator, Sponsor, and appropriate regulatory authorities, as required, concur that the benefit-risk is positive. One overall CNTY-101 RP2R will be declared in Part 1. Part 2, expansion, will further evaluate the safety, pharmacokinetics (PK), and efficacy of the CNTY-101 regimen, treating up to an additional 12 subjects to reach a total of approximately 20 subjects treated at the RP2R. In addition to safety and efficacy endpoints, the trial will evaluate exploratory PK, immunogenicity and pharmacodynamic endpoints including evaluations of tumor cfDNA, iNK tumor trafficking and serum cytokines. Clinical trial information: NCT05336409 .
A phase 1/2 study of STP938, a first-in-class inhibitor of CTP synthase 1, in patients with relapsed/refractory B or T cell lymphoma.
Authors: Patel Manish R. , Ahearne Matthew , Linton Kim , Fox Christopher , Lewis David John , Higgins Maureen , Schwartz Brian E. , Beer Philip A , Tees Michael Timothy 
Published: June 2023

TPS7591 Background: The rate limiting step in de novo pyrimidine synthesis is catalyzed by two homologous enzymes, CTPS1 and CTPS2. CTPS1 is essential for lymphocyte proliferation, whereas CTPS2 is sufficient in non-haemopoietic cells. STP938 is a first in class oral CTPS1 inhibitor showing > 1,300-fold selectivity over CTPS2. In preclinical studies, STP938 induced death of cancer cells by apoptosis at nanomolar concentrations, and inhibited tumor growth in in vivo models of hematological malignancies. Methods: The study employs a seamless dose escalation, dose expansion design. The phase 1 dose escalation follows a standard 3+3 approach. Intra-patient dose escalation will be permitted. The recommended phase 2 dose (RP2D) will be nominated based on safety, target engagement and early signs of efficacy. An additional six patients will be treated at the RP2D with a preliminary assessment of food effect. Key phase 1 endpoints are safety and tolerability. Key phase 2 endpoints are objective response rate and duration of response. The study is open to adult patients following at least 2 prior lines of therapy who have no treatment options known to provide clinical benefit. The phase 1 study is recruiting patients with B or T cell lymphoma; the phase 2 study will be limited to cohorts of patients with specific lymphoma subtypes, which may include T cell lymphoma (peripheral or cutaneous), mantle cell lymphoma, indolent B cell lymphoma and diffuse large B cell lymphoma. Standard exclusion criteria apply; patients with ECOG performance score > 2 or known CNS involvement by lymphoma are not eligible. The phase 2 study will follow a Simon two-stage design with an interim analysis for futility based on predefined, lymphoma subtype specific response rates. In the case of STP938 showing promising efficacy, provision is included in the protocol to expand a cohort using an adaptive approach based on early efficacy signals (Mehta and Pocock, 2011). Target engagement is assessed by measuring cytokine release (TNFα, IFNγ, IL2, IL8) from ex vivo stimulated patient T cells. Exploratory studies include pre- and on-treatment lymphoma biopsies to assess biomarkers of response and mechanism of action. Tumor genomics will be assessed by sequencing of circulating tumor DNA prior to treatment and at disease progression using a bespoke genomic assay designed to elucidate biomarkers of response and understand mechanisms of resistance. The phase 1 study (NCT05463263) opened to enrolment in the US and UK in September 2022. No dose limiting toxicities were observed in the first cohort of 3 patients. The phase 2 study will include additional centers in France. Clinical trial information: NCT05463263 .
OMNIA-2: Phase I/II study of ANV419, an IL-2R-βγ targeted antibody-IL-2 fusion protein, in patients with relapsed or refractory multiple myeloma.
Authors: Hess Dagmar , Fladeland Iversen Katrine , Mateos Maria-Victoria , Pabst Thomas , Rosiñol Laura , Kovacikova Jana , Jethwa Schnetzler Sangeeta 
Published: June 2023

TPS8068 Background: ANV419 is a potent, selective IL-2Rβγ targeted antibody IL-2 fusion protein, designed to enable the delivery of high dose interleukin-2 (IL-2) to patients, in order to stimulate anti-tumour response and minimise toxicities. The ANV419-001 first-in-human study (NCT 04855929) demonstrated that ANV419 preferentially stimulates cytotoxic CD8+ T and natural killer (NK) cells over immunosuppressive regulatory T cells, with a significantly longer half-life than that of conventional IL-2. The safety and tolerability data from this study confirmed that ANV419 delivers high molar equivalents of IL-2 in a tolerable and convenient way. In patients with multiple myeloma, the critical role of NK cells has been well described. ANV419 is expected to promote antitumor response via the preferential stimulation of cytotoxic CD8+ T and NK cells. Methods: The OMNIA-2 study (ANV419-102; NCT 05641324) will evaluate safety and preliminary efficacy of ANV419 as monotherapy and in combination with daratumumab (dara), or lenalidomide with low dose dexamethasone (lena/dex), in patients with relapsed or refractory multiple myeloma. OMNIA-2 is a Phase I open-label, multi-center study in adult patients (n = 52) with symptomatic multiple myeloma who responded to previous treatment and received autologous stem cell transplant, or at least 2 lines of therapy including an immunomodulator, proteasome inhibitor, and/or dara. The study is conducted in 2 stages using a Bayesian Optimal Phase 2 approach. Stage 1 consists of a run-in phase with subsequent randomization to ANV419 243mcg/kg or ANV419 108mcg/kg for 8 weeks, followed by a second randomisation to ANV419 108mcg/kg in combination with lena/dex or dara for a further 8 weeks. Stage 2 follows a similar design as stage 1 and consists of a monotherapy run-in phase with either high or low dose ANV419, with a second randomisation to ANV419 108mcg/kg in combination with either lena/dex or dara, according to the safety and efficacy observed in Stage 1. ANV419 is administered intravenously over 15 to 20 minutes every two weeks. Lena, dex and dara are administered at their respective approved dosing regimens. Tumour response is determined using IMWG (2016) response criteria. AEs are assessed according to CTCAE V5.0. OMNIA-2 is being conducted in Denmark, France, Germany, Spain, Switzerland, UK and enrolment began in January 2023 and preliminary data are expected in Q1 2024. Clinical trial information: NCT05641324 .
A phase II study to evaluate the efficacy and safety of combination therapy of durvalumab (MEDI4736) and amrubicin in patients with recurrent small cell lung cancer (SCLC): Aphrodite trial, in progress.
Authors: Kato Yuka , Ohashi Kadoaki , Kozuki Toshiyuki , Kuyama Shoichi , Yamaguchi Kakuhiro , Yokoyama Toshihide , Uno Hideki , Yoshida Michihiro , Hattori Noboru , Hotta Katsuyuki , Kiura Katsuyuki 
Published: June 2023

TPS8612 Background: Immunochemotherapy (ICT) is the standard first-line treatment for extensive stage (ES)-SCLC. However, progression-free survival for patients (pts) treated with ICT as first-line therapy is approximately 5 months, and half of the pts will relapse within 6 months. Several drugs have been approved for the treatment after relapse, and amrubicin has been used as a second-line treatment in Japan for 20 years. However, the efficacy of pts treated with amrubicin is unsatisfactory, the median survival was 9.2 months (pts with sensitive relapse (SR-pts)) and 2.6 months (pts with refractory relapse (RR-pts)), indicating an urgent need for new therapeutic strategies in the treatment of post-relapse SCLC pts. A retrospective study showed significant improvement in survival for patients who progress on immunochemotherapy, treated with same ICI plus chemotherapy as second-line therapy (Trans Lung Cancer Rec. 2020). Cytotoxic chemotherapy introduced immunogenic cell death and the addition of chemotherapy to ICI might have a synergistic effect. Based on these assumptions, the combination of amrubicin with ICI may provide additional benefit for post-progression pts and we are therefore initiating this study. Methods: This is an open-label, single-arm, multicenter, physician-initiated Phase 2 study of amrubicin plus durvalumab in Japanese pts with relapsed SCLC. The study is divided into a lead-in cohort (LIC) and a Phase 2 part; the LIC will use a 3+3 design to ensure safety and will proceed to the Phase 2 part if the first 3 pts have no dose limiting toxicity (DLT) or the first 6 pts have only 1 DLT. Eligibility criteria include pts with ES-SCLC who relapse after platinum-containing chemotherapy with durvalumab as first-line therapy, age ≥20, ECOG 0-1. The primary endpoint is 1-year survival. Patients were treated with intravenous amrubicin 40 mg/m2 on day 1-3 and durvalumab 1500 mg/body on day 1 every 3 weeks until PD or unacceptable toxicity. The planned number of pts was 18 each with sensitive relapse (SR-pts) and refractory relapse (RR-pts) which was calculated based on the results of a previous randomized controlled trial (J Clin Oncol. 2008). In this trial, the point estimates and two-sided 90% confidence intervals (Clopper Peason method) for 1-year survival corresponding to the expected 1-year survival were: SR-pts (11/18 patients): 0.611 (90% CI: 0.392-0.801), RR-pts (8/18 0.444 (90% CI: 0.244-0.659). Enrollment began in October 2022, and will be completed by March 2025. Clinical trial information: jRCT2061220036 .
Phase 2 study of telisotuzumab vedotin (Teliso-V) monotherapy in patients with previously untreated MET-amplified locally advanced/metastatic non-squamous non-small cell lung cancer (NSQ NSCLC).
Authors: Horinouchi Hidehito , Shibata Yuji , Looman Jim , Sui Yunxia , Noon Elysa , Lu Shun 
Published: June 2023

TPS9149 Background: Teliso-V is a first-in-class anti–c-Met antibody-drug conjugate composed of the monoclonal antibody telisotuzumab (ABT-700), a cleavable valine-citrulline (dipeptide) linker, and cytotoxic monomethylauristatin E (MMAE; potent microtubule polymerization inhibitor). Direct MMAE payload delivery to c-Met protein overexpressing (OE) cells enables Teliso-V to work independently of c-Met signaling. In NSCLC, while c-Met OE is more common than MET gene amplification (Amp), about 90% of MET Amp tumors will also be c-Met OE. In an ongoing phase 2 trial, Teliso-V showed encouraging efficacy and acceptable safety in previously treated c-Met OE NSQ NSCLC population (Camidge et al. JCO.2022.40.16_suppl.9016). From this study, a retrospective analysis of 10 patients with MET Amp (≥1.8 MET gene to chromosome 7 copy number ratio by fluorescence in situ hybridization [FISH]) demonstrated an objective response rate (ORR) of 80%. Described here is an ongoing phase 2 study evaluating efficacy and safety of Teliso-V monotherapy in patients with previously untreated MET Amp locally advanced/metastatic NSQ NSCLC. Methods: This is a phase 2, single-arm, open-label, global study (NCT05513703). Eligible patients (≥18 years) have histologically documented advanced/metastatic NSQ NSCLC, measurable disease by RECIST v1.1, confirmed MET Amp determined centrally by FISH or locally by FISH, tissue next-generation sequencing (NGS), or plasma NGS using sponsor-approved assays. Additional eligibility criteria include Eastern Cooperative Oncology Group performance status 0 or 1, no alterations in EGFR, ALK, ROS1, or BRAF that predict sensitivity to targeted therapy, no prior systemic therapy for locally advanced or metastatic NSCLC, no prior c-Met–targeted antibody therapy. Teliso-V is administered intravenously at 1.9 mg/kg every 2 weeks until disease progression, intolerable toxicity, or other study drug discontinuation criteria are met. Primary endpoint is ORR assessed by independent central review (ICR). Secondary endpoints include duration of response and disease control rate, progression-free survival per ICR, overall survival, patient-reported outcomes (PROs). Tumor assessments (per RECIST v1.1) are performed at baseline and approx. every 6 (year 1), 8 (year 2), and 12 weeks (year 3 and beyond). PROs are assessed through validated questionnaires (EORTC QLQ-LC13, EORTC QLQ-C30, EQ-5D-5L). Safety and tolerability are evaluated by adverse events, physical examinations, laboratory data, and vital signs. Pharmacokinetic and biomarker evaluations may be used for exploratory analyses. The trial intends to enroll approx. 70 efficacy-evaluable patients, with interim analyses planned after 20 and 50 patients are able to be followed for ≥6 months. The study was open to enrollment as of Nov 2022. Clinical trial information: NCT05513703 .