bluuebunny/crossref_metadata_2025_split huggingface dataset:
Camrelizumab combined with TIP (paclitaxel+cisplatin+ifosfamide) as neoadjuvant treatment of locally advanced penile cancer before lymphadenectomy: An exploratory, phase Ⅱ study.
Authors: Chen Yongsheng , Wei Liangjun , Teng Lichen , Cao Yan , Li Dechao , Wang Wentao , Pan Hongxin , Wang Xingyuan , Xu Songlin , Wang Huang , Wang Yanjie , Zhang Yuling , Li Changfu 
Published: June 2022

TPS5093 Background: Penile squamous cell carcinoma (PSCC) is a highly aggressive disease that accounts for 95% of penile cancers and is characterized by a high risk of early locoregional spread and morbidity with subsequent potential for distant dissemination. The lymph node invasion is one of the most important factor that affects the prognosis of PSCC. Penile cancer patients with uninvolved inguinal lymph nodes had a 5-year survival rate of 66% compared with 27% for those with involvement, and penile cancer with the pelvic lymph node involvement have a worse 5-year survival rate that is typically less than 10%. Therefore, this study aims to reduce small lesions to reach the radical lymphadenectomy by camrelizumab combined with TIP in the neoadjuvant treatment of PSCC. Methods: In this single-arm, prospective, phase Ⅱ study, 34 patients with histological or cytological diagnosis of locally advanced PSCC (TX, N2-N3, M0), ECOG performance score of 0-1, planned to be recruited. Enrolled patients with inguinal and/or pelvic lymph node metastasis (positive percutaneous lymph node biopsy) after primary tumor resection of penile cancer were treated with combined therapy including camrelizumab (200 mg, iv, Q3W), paclitaxel (175 mg/m2, iv, Q3W), cisplatin (25 mg/m2, iv, Q3W) and ifosfamide (1200 mg/m2, iv, Q3W) for a total of 4 cycles. The primary endpoint is the rate of pathologic complete response (pCR). Secondary endpoints are event-free survival, overall survival, objective response rate, disease control rate and safety. On the basis of a threshold pCR rate of 13.6%, targeting an expected pCR of 34% and assuming 12 months follow-up, 80% power and a one-sided α = 0.05, this design requires 34 evaluable patients to be accrued over 3 years. Clinical trial information: ChiECRCT20210503.
AGO-OVAR 28/ENGOT-ov57: Niraparib versus niraparib in combination with bevacizumab in patients with carboplatin-taxane based chemotherapy in advanced ovarian cancer—A multicenter, randomized, phase III trial.
Authors: Heitz Florian , Marth Christian , Henry Stephanie , Reuss Alexander , Cibula David , Gaba Lydia , Colombo Nicoletta , Polleis Sandra , Harter Philipp 
Published: June 2022

TPS5612 Background: Standard of care chemotherapy in patients (pts) with advanced ovarian cancer (AOC) is the combination of carboplatin and paclitaxel. Data from the PRIMA trial has shown a significant benefit in pts by the addition of a maintenance treatment (MT) with niraparib irrespective of BRCA or HRD-status in high-grade ovarian cancers (OC). The PAOLA-1 trial evaluated MT in pts with AOC with the combination of olaparib and bevacizumab and has also shown a significant benefit compared to bevacizumab monotherapy. However, it is unclear if a PARP-inhibitor (PARPi) MT monotherapy is sufficient or if the addition of bevacizumab is needed. Therefore, we investigate, if the treatment strategy of carboplatin / paclitaxel / bevacizumab / PARPi is superior to the treatment of carboplatin / paclitaxel / PARPi in an all-comer population. Methods: AGO-OVAR 28/ ENGOT-ov57 (NCT05009082; EudraCT Number: 2021-001271-16) is an Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Study Group led, international, multicenter, randomized, prospective phase III trial within the ENGOT trial network. The trial population is composed of adult pts with newly diagnosed, advanced high-grade epithelial OC, primary peritoneal cancer or fallopian tube cancer FIGO III/IV (except FIGO IIIA2 without nodal involvement). All pts should have completed the first cycle of chemotherapy (carboplatin and paclitaxel) as part of Study Run-In-Period. Prior to day1 of cycle2, pts with a valid central tumor BRCA ( tBRCA) test result will be randomized 1:1 into either Arm1 and will receive 5 additional cycles of carboplatin and paclitaxel, q21d followed by niraparib for up to 3 years; or into Arm2 where pts will receive 5 additional cycles of carboplatin and paclitaxel plus bevacizumab, q21d followed by bevacizumab, q21d (for up to 1 year) and niraparib for up to 3 years. Patients who are scheduled for neoadjuvant chemotherapy and interval debulking surgery are also allowed to be included in the trial. The primary objective is progression free survival (PFS). Secondary objectives include but are not limited to: PFS according to tBRCA-status, overall survival, PFS2, safety and tolerability, and quality of life. The trial will start in Q1/2022 with First Patient First Visit expected in Q2/2022. It is planned to recruit 970 patients. Clinical trial information: NCT05009082.
TEDOVA/GINECO-OV244b/ENGOT-ov58 trial: Neo-epitope based vaccine OSE2101 alone or in combination with pembrolizumab versus best supportive care (BSC) as maintenance in platinum-sensitive recurrent ovarian cancer with disease control after platinum.
Authors: Leary Alexandra , Deluche Elise , Favier Laure , Paoletti Xavier , Mansi Laura , Tredan Olivier , Eberst Lauriane , De La Motte Rouge Thibault , Joly Florence , Lortholary Alain , You Benoit , Marmé Frederik , Van Gorp Toon , Floquet Anne , Frenel Jean-Sebastien 
Published: June 2022

TPS5614 Background: Besides PARP inhibitors and bevacizumab, there are no approved maintenance therapies after platinum based chemotherapy for patients with a platinum sensitive relapsed epithelial ovarian cancer (OC). Immune checkpoint inhibitors (ICI) as single agents have limited activity in OC. One attractive strategy is to turn OC from immunogenic “cold” to “hot” tumors via vaccination with tumor-associated antigens (TAAs). OSE2101 is a multiple-neoepitope vaccine restricted to HLA-A2-positive patients (45% of OC patients) targeting 5 TAAs: TP53, MAGE2, MAGE3, CEA and HER2. These neo-epitopes are modified to increase both major histocompatibility complex and the T cell receptor binding affinity. The proof of concept for this approach was recently demonstrated with OSE2101 improving overall survival in a phase III trial in lung cancer progressing after ICI (Besse et al. 2021). The combination of OSE2101 with an ICI may most effectively harness anti-tumor immunity. Methods: TEDOVA is an international randomized open-label, phase II trial evaluating the benefit of maintenance by OSE2101 alone or in combination with PD1 inhibition (pembrolizumab) after platinum based chemotherapy in relapsed OC, previously treated with bevacizumab (if eligible) and a PARP inhibitor (if eligible). Patients (N=180) with CR/PR/SD at the end of chemotherapy are randomized (1:1:2) to: Observation/BSC (Arm A), OSE2101 alone (Arm B), or OSE2101 in combination with pembrolizumab (Arm C). Experimental treatments are continued until progression, or intolerance, for up to 2 years. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall response rate, safety, time to subsequent first or second treatment (TTST-1, TTST-2) and overall survival. 180 HLA-A*02 positive patients will be randomized. HLA-A*02 negative patients will be followed in a separate observational cohort. The sample size is calculated to provide 90% power to detect an improvement in PFS for Arm C vs Arm A with a HR of 0.57. Three one-sided Log-rank tests will be considered in a pre-defined sequence: H1: C (OSE2101+pembrolizumab) vs A (BSC); H2: C (OSE2101+pembrolizumab) vs B (OSE2101) and H3: B vs A. The type I error will be α=5%. The type II error will be β=10%. Tests will be one-sided. Status: The TEDOVA/GINECO-OV244b/ENGOT-ov58 trial is currently recruiting. Clinical trial information: NCT04713514.
Phase 2 trial of enoblituzumab plus retifanlimab or tebotelimab in first-line treatment of patients (pts) with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Authors: Obara Grzegorz , Sun Jichao , Loo Deryk , Bohac Gerry C. 
Published: June 2022

TPS6102 Background: Head and neck cancer accounts for ̃900,000 cases and over 400,000 annual deaths worldwide as of 2021. Pts with R/M SCCHN have a poor prognosis with median overall survival <1 year. Programmed death (PD)-protein 1 (PD-1) and PD-ligand 1 (PD-L1) blockade has shown antitumor activity in advanced SCCHN. Enoblituzumab (MGA271) is an investigational monoclonal antibody (mAb) that binds B7-homolog 3 (B7-H3) with enhanced binding to the activating Fc gamma receptor CD16A, particularly the low-affinity allele CD16A-158. B7-H3 is overexpressed in many cancers, including SCCHN, but not in most normal tissues. Retifanlimab (MGA012, INCMGA00012) is an investigational anti-PD-1 mAb, blocking binding of PD-L1 or PD-ligand 2 (PD-L2) to PD-1. Tebotelimab (MGD013) is an investigational, Fc-bearing bispecific, tetravalent DART® molecule designed to bind PD-1 and lymphocyte activation gene 3, inhibiting their interaction with PD-L1 or PD-L2 and major histocompatibility complex class II. In vitro data suggest that both retifanlimab and tebotelimab have potential to sustain enoblituzumab-mediated immune activation and antitumor activity (Obara G, et al. Ann Oncol. 2021;32[suppl 5]:S814). Combination of enoblituzumab with retifanlimab or tebotelimab sustained the ability of natural killer cells and CD8+ T cells to produce interferon gamma upon restimulation. Both retifanlimab and tebotelimab enhanced enoblituzumab-dependent cytotoxicity targeting B7-H3–expressing tumor cells. In a phase 1/2 study, the combination of enoblituzumab with pembrolizumab was well tolerated (Aggarwal C, et al. J Immunother Cancer. 2022 [under review]). The overall response rate in anti-PD-1/PD-L1–naïve pts with SCCHN (post platinum) was 33% (6/18), including 1 confirmed complete and 5 confirmed partial responses, warranting further development of this combination in R/M SCCHN. Methods: This is an open-label, nonrandomized study in first-line treatment of pts with R/M SCCHN. Approximately 50 pts with PD-L1 combined positive score (CPS) ≥1 will receive enoblituzumab 15 mg/kg plus retifanlimab 375 mg and 30 pts with CPS <1 will receive enoblituzumab 15 mg/kg plus tebotelimab 600 mg. Dosing is once every 3 weeks with tumor assessment at the end of Cycle 2 and every 3 cycles thereafter. Pts with no prior systemic therapy for R/M SCCHN are eligible. Pts who completed systemic therapy >6 months before the study, if given as part of multimodal treatment for locally advanced disease, are eligible. In the tebotelimab cohort, safety data will be reviewed for dose-limiting toxicities through Cycle 2 Day 7 on the first 12 pts (2 mini cohorts of 6 pts each). All pts will be followed for survival after the last dose of study drug. The first pt was enrolled in March 2021, and 28 pts are on treatment as of January 19, 2022. Clinical trial information: NCT04634825.
A phase 1, first-in-human, drug dose-escalation study of RM-1995 photoimmunotherapy, as monotherapy or combined with pembrolizumab, in patients with advanced cutaneous squamous cell carcinoma or with head and neck squamous cell carcinoma.
Authors: Cognetti David M. , Curry Joseph M. , KuklÃk Rostislav , Gillenwater Ann M. 
Published: June 2022

TPS6103 Background: RM-1995 comprises an antibody against CD25, conjugated with a light-activatable dye (IRDye 700DX), which can subsequently be activated by illumination with 690 nm non-thermal red light for precise, targeted cell killing. Administration of the antibody-dye conjugate followed by local illumination results in target cell membrane disruption, while limiting damage to surrounding tissue. CD25 (lL-2Rα) is highly expressed by regulatory T cells (Tregs), thereby providing an opportunity to specifically target intratumoral Tregs for depletion via photoimmunotherapy. Tregs are critical in promoting immune homeostasis; however, in the context of solid tumors, Treg-mediated suppression detrimentally constrains anticancer T-cell responses, and a low ratio of CD8+ T cells:Tregs in the tumor is negatively correlated with clinical outcomes. Preclinical data suggest that RM-1995 photoimmunotherapy treatment alleviates local Treg-mediated restraint within the tumor microenvironment. Anticancer responses were further improved when combined with anti-PD-1 checkpoint inhibition. Methods: A phase 1 first-in-human dose-escalation study of RM-1995 photoimmunotherapy as monotherapy, or in combination with pembrolizumab, in patients with advanced cutaneous squamous cell carcinoma (cuSCC) and head and neck squamous cell carcinoma (HNSCC) is now enrolling (NCT05220748). The phase 1a portion will evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent RM-1995 photoimmunotherapy and determine the maximum tolerated dose or maximum administered dose of RM-1995 with a fixed light dose for tumor illumination. The phase 1b portion will include combination therapy with pembrolizumab. Enrolled patients will receive RM-1995 IV, followed 24±4 hours later by local tumor illumination. Pembrolizumab (200 mg) will be administered 5–7 days prior to RM-1995 infusion, then again 3 weeks later. Patients may be eligible to receive repeated photoimmunotherapy cycles for up to 12 months. Primary outcomes include safety and tolerability, and dose finding. The study will include cuSCC or HNSCC patients with locally advanced or locoregional disease with or without metastases that has recurred or progressed on or after platinum-based chemotherapy, and who are not eligible for further locoregional treatment. Other criteria include ECOG 0–2 and having ≥1 tumor accessible for illumination. Key exclusion criteria are: tumor sites located in sensitive or vital anatomic structures or invading a major blood vessel (unless treated to prevent hemorrhage); and other clinically significant or uncontrolled disease processes. An estimated 18 patients will be enrolled into each portion of the study. Clinical trial information: NCT05220748.
CRC-403: A phase 1/2 study of bbT369, a dual targeting CAR T-cell drug product with a gene edit, in relapsed and/or refractory B-cell non-Hodgkin lymphoma (NHL).
Authors: Locke Frederick L. , Miklos David Bernard , Tees Michael Timothy , Li Aojun , Truppel-Hartmann Anna , Flinn Ian W. 
Published: June 2022

TPS7580 Background: Although CD19 directed CAR T cell therapies have improved outcomes for non-Hodgkin's lymphoma (NHL) patients, only about 30-40% of 3L+ patients obtain long term remission after this treatment (Neelapu et al. 2017; Schuster et al. 2019). bbT369, a next generation, dual targeted (CD79a/CD20), gene edited (CBLB gene knock out) autologous CAR T cell therapy was devised to overcome hypothesized mechanisms of CD19 CAR T cell treatment failure including loss/downregulation of target antigen, loss of co-stimulation pathways on tumor cells, exhaustion of CAR T cells, and CAR T cell dysfunction due to an immunosuppressive microenvironment (Shah and Fry 2019). bbT369 uses an OR gated design to limit antigen escape and contains split costimulatory domains (CD28 and 41BB) to enhance T cell activation. Methods: CRC-403 (NCT05169489) is a non-randomized, open label, multi-site phase 1/2 study enrolling relapsed and/or refractory B cell non-Hodgkin’s lymphoma (NHL), including diffuse large B cell lymphoma (DLBCL), high-grade B cell lymphoma (HGBCL), primary mediastinal (thymic) large B cell lymphoma (PMBCL), follicular lymphoma (FL) 3b, and DLBCL transformed from FL (tFL). Patients must have relapsed after ASCT or at least 2 prior lines of therapy. Patients with tFL must be relapsed after receipt of ASCT or at least 2 prior therapies after documentation of transformation. Patients with previous exposure to non-investigational CD19 directed CAR T cell therapy who did not experience disease progression within 6 weeks of initial CAR T cell infusion are eligible for enrollment. Approximately 50 patients will be enrolled in the phase 1 portion. The primary endpoints of the phase 1 portion are determination of the MTD, determination of recommended phase 2 dose (RP2D) and safety. Secondary endpoints include overall response rate, complete response rate, time to response and time to next anti-lymphoma treatment. Exploratory endpoints include DOR, PFS, OS, CAR+ T cell expansion and correlations between clinical response and T cell phenotype or antigen expression on tumor cells. The starting dose of bbT369 will be 50x106 CAR+ T cells and a BOIN design will be used for dose escalation/de-escalation decisions during the study. Upon establishment of the RP2D, the phase 2 portion will begin enrollment. Clinical trial information: NCT05169489.
Open-label, active-control, phase 2/3 study of zilovertamab vedotin plus standard of care in patients with relapsed or refractory diffuse large B-cell lymphoma.
Authors: Cobb Patrick Wayne , Zhou Heng , Nahar Akash , Marinello Patricia 
Published: June 2022

TPS7592 Background: Consensus treatment guidelines are unavailable for patients with diffuse large B-cell lymphoma (DLBCL) whose disease progresses after first-line therapy. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a transmembrane protein that is overexpressed in multiple cancers, including hematological malignancies. Zilovertamab vedotin (ZV; MK-2140, previously known as VLS-101), an antibody-drug conjugate comprising a humanized IgG1 monoclonal antibody, a proteolytically cleavable linker, and the antimicrotubule cytotoxic agent monomethyl auristatin E, targets ROR1 and has shown promising efficacy and tolerability in hematological malignancies, including DLBCL. This 2-part (part 1, dose confirmation; part 2, dose expansion), open-label, randomized, active-control, phase 2/3 study (NCT05139017) will assess safety and efficacy of ZV + standard of care in patients with relapsed/refractory (R/R) DLBCL. Methods: Eligible adult patients must have histologically confirmed DLBCL per WHO classification, ineligible for or have failed autologous stem cell transplantation and chimeric antigen receptor T cell therapy, R/R DLBCL after ≥1 line of prior therapy (cohort A) or ≥2 lines of prior therapy (cohort B), measurable disease per Lugano 2014 criteria, and Eastern Cooperative Oncology Group performance status ≤2. Approximately 420 patients will be enrolled in the study (cohort A, n = 230; cohort B, n = 190). In the part 1 dose confirmation phase, 30 patients from cohort A will receive ZV (at increasing doses: 1.5, 1.75, 2.0, 2.25, and 2.5 mg/kg; starting at 1.75 mg/kg) plus gemcitabine-oxaliplatin + rituximab (R-GemOx) to establish the recommended phase 2 dose using the mTPI design. A safety run-in phase of part 2 will include 30 patients from cohort B and will receive ZV + bendamustine and rituximab (BR). Approximately 360 patients will be included in the part 2 dose expansion phase (cohort A, n = 200; cohort B, n = 160). Patients from cohort A will be randomly assigned 1:1 to 6 cycles of either ZV + R-GemOx or R-GemOx. Patients from cohort B will be randomly assigned 1:1 to 6 cycles of either ZV + BR or BR. Disease response assessments by CT and PET scans will occur every 12 weeks until disease progression or study discontinuation. Adverse events (AEs) will be monitored throughout the study and graded per NCI CTCAE version 5.0. In part 1, the primary end point is safety, including DLTs, AEs, and discontinuation due to AEs. The primary end point for cohorts A and B in the dose expansion phase of part 2 will be progression-free survival by blinded independent central review per Lugano 2014 criteria. Key secondary end points in the dose expansion phase of part 2 for both cohorts include objective response rate (including complete response and partial response) and duration of response, both per Lugano 2014 criteria and overall survival. Clinical trial information: NCT05139017.
A first-in-human phase 1 study of the next-generation RET inhibitor, LOXO-260, in RET inhibitor refractory patients with RET-altered cancers (trial in progress).
Authors: Pennell Nathan A. , Wirth Lori J. , Gainor Justin F. , Rotow Julia K , Johnson Melissa Lynne , Bauer Todd Michael , Kroiss Matthias , Sukrithan Vineeth , Kang Hyunseok , Worden Francis P. , Bestvina Christine M. , Hadoux Julien , Cassier Philippe Alexandre , Italiano Antoine , Wolf Juergen , Brose Marcia S. , Avsar Emin , Axelson Michael D. , Subbiah Vivek , Drilon Alexander E. 
Published: June 2022

TPS8595 Background: RET fusions are found in 1-2% of lung adenocarcinomas and 10-20% of papillary thyroid carcinomas. Activating RET mutations occur in 50-60% of medullary thyroid cancers (MTCs). Selpercatinib was the first selective RET inhibitor approved by the FDA and is indicated for patients (pts) with RET fusion-positive NSCLC and thyroid cancer, and RET mutant MTC. Despite marked and durable activity, acquired resistance can eventually develop through a variety of mechanisms. These include acquisition of RET G810X mutations at the solvent front of the ATP pocket. LOXO-260 is a highly potent and selective inhibitor of RET designed to have activity against both solvent front and gatekeeper mutations, expressed alone or together, while maintaining potency against RET fusions or mutations (Kolakowski GR. et al. 2021 Cancer Research 81 (13 Suppl) 1464). Methods: LOXO-NGR-21001 is a global, open-label, first-in-human phase 1 study of LOXO-260 in pts with RET fusion-positive advanced solid tumors and RET mutant MTC who received a prior selective RET inhibitor. Phase 1a dose escalation will utilize a modified i3+3 design, allowing for pt backfill to previously cleared dose levels. Phase 1b dose expansion will evaluate LOXO-260 in specific expansion cohorts: RET fusion-positive NSCLC or thyroid cancers and RET mutant MTC. The primary objectives in dose escalation are to determine the MTD/RP2D and safety of LOXO-260. Key secondary objectives include characterization of PK and preliminary antitumor activity of LOXO-260 per RECIST v1.1. The primary objective of dose expansion is to assess the antitumor activity of LOXO-260 based on investigator-assessed overall response rate (ORR). Key secondary objectives are to characterize the PK and antitumor activity of LOXO-260 based on progression-free survival (PFS), time to response (TTR), and duration of response (DOR). Eligible pts must have received a prior selective RET inhibitor, have a documented RET fusion or RET mutation and a diagnosis of locally advanced, unresectable and/or metastatic cancer per disease-specific criteria, and must have progressed or be intolerant to standard therapies or must have refused such a therapy. Pts must be ≥18 years old and have an ECOG PS of 0-2. Key exclusion criteria include presence of serious cardiac conditions, interstitial lung disease, symptomatic CNS metastases, or carcinomatous meningitis. Clinical trial information: NCT05241834.