bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 3 study of the subcutaneous programmed cell death protein 1 inhibitor sasanlimab as single agent for patients with bacillus Calmette-Guérin, unresponsiv,e high-risk, non-muscle invasive bladder cancer: CREST Study Cohort B.
Authors: Shore Neal D. , Powles Thomas , Bedke Jens , Galsky Matt D. , Kopyltsov Evgeny , Necchi Andrea , Palou Joan , Vermette Jennifer J. , Randall Alison E. , Pierce Kristen J. , Cesari Rossano , Steinberg Gary D.
Published: June 2022

TPS4614

Background: Bacillus Calmette-Guérin (BCG) therapy is the standard of care for high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor. However, disease recurrence or progression is common and patients with BCG-unresponsive disease are unlikely to respond to further BCG therapy. In these patients, the current standard of care is radical cystectomy and bladder-preserving treatment options, limited to intravesical chemotherapy or intravenous pembrolizumab. In a phase 1 study, sasanlimab (PF-06801591), a monoclonal antibody to programmed cell death protein 1 (PD-1), was administered subcutaneously at 300 mg every 4 weeks. Sasanlimab had an acceptable safety profile and showed clinical activity aligned to other anti-PD-1/PD-ligand 1 (PD-L1) agents in patients with advanced urothelial carcinoma and non-small cell lung cancer, while offering the convenience of subcutaneous administration. Therefore, CREST Study Cohort B aims to evaluate sasanlimab administered subcutaneously in patients with BCG-unresponsive NMIBC. Methods: CREST Study Cohort B is a non-randomized, multicenter, multinational, open-label, phase 3 study and will enroll ̃160 patients with histologically confirmed BCG-unresponsive, high-risk, non-muscle invasive transitional cell carcinoma of the bladder urothelium (high-grade Ta or T1 tumor, or carcinoma in situ [CIS]) in 2 separate Cohorts, B1 and B2 (̃110 and ̃50 patients, respectively). Cohort B1 will enroll patients with persistent or recurrent CIS with or without concomitant recurrent high-grade Ta/T1 disease, within 12 months of completing adequate BCG therapy. Cohort B2 will enroll patients with recurrent high-grade Ta/T1 disease within 6 months of completing adequate BCG therapy. All patients will receive subcutaneous sasanlimab as a single agent. Efficacy will be assessed at regular intervals by cystoscopy, urine cytology, biopsy, and imaging. The primary endpoint is complete response (CR) and event-free survival (EFS) for Cohort B1 and B2, respectively. Secondary endpoints include duration of CR (Cohort B1 only), EFS (Cohort B1 only), overall survival, time to cystectomy, safety, health-related quality of life, pharmacokinetic parameters, PD-L1 expression, and incidence of anti-drug antibodies. Recruitment of patients in CREST Study Cohort B will be opened in Canada and the United States of America, with other sites in Asia, Australia, and Europe. Clinical trial information: NCT04165317.
ETCTN 10437: A single-arm phase II study of bone-targeted sn-117m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases.
Authors: Myint Zin , St Clair William H. , Wang Peng , Khouli Riham , Lemieux Bryan P , Cheek Dennis , Yan Donglin , Kunos Charles
Published: June 2022

TPS5095

Background: Most patients with metastatic castration resistant prostate cancer (mCRPC) develop bone metastases with debilitating pain that is itself associated with shorter survival. Several bone-seeking radionuclides have been developed for palliation of metastatic bone pain. To date, radium-223 dichloride is the first and only approved targeted alpha therapy for mCRPC; the major dose limitation is bone marrow toxicity with modest pain relief. Sn-117m-diethylenetriaminepentaacetic acid (DPTA), is a complex of a radioisotope of tin with DTPA. It emits a low-energy conversion electron and also yields a gamma emission. Sn-117m-DPTA localizes selectively in bone, and the limited range (0.2-0.3 mm) of its conversion electrons resulting in deeper tissue penetration with less radiation effects on bone marrow as compared to radium-223 dichloride. Srivastava et al. (1998) reported in a phase I/II study of patients with painful bone metastases from a variety of solid tumors, 45% of patients obtained reduction of pain by at least 50%, and 30% had complete relief of pain for more than two weeks after one injection. Thus, Sn-117m-DTPA has high palliative efficacy with little significant toxicity. Additional evaluation of this agent in mCRPC patients is urgently required. Methods: The study is a phase 2 single-arm clinical trial of Sn-117m-DPTA (20 mCi/70Kg or 0.28 mCi/kg) intravenously every 8 weeks for two injections for patients with mCRPC metastatic to at least two bone sites with at least one clinically meaningful pain site at baseline. Re-treatment with additional two cycles is allowed if patients meet re-treatment criteria. Key eligibility criteria include 1) refractory mCRPC patients who progressed on any lines of therapies 2) self-reported bone pain (≥4 on an 11-point pain intensity scale), and 3) must be on either regular pain medication or have undergone palliative radiation for bone pain within 12 weeks prior to starting study treatment. Key exclusion criteria include 1) visceral metastases and 2) malignant lymphadenopathy exceeding 3cm in short-axis diameter. Twenty-five patients will be enrolled with a primary objective to assess the efficacy of Sn-117m-DTPA on sustained pain response; defined as 1) achieving pain index ≤3 index within a 12-week period and 2) maintaining pain index ≤3 over a 16-week period. Secondary endpoints include patient reported outcomes, adverse events, progression-free survival and overall survival. Correlative aims include assessing blood (systemic inflammatory markers) and tissue biomarkers (gene sequencing and polo-like kinase-1) for association with clinical benefit. An interim analysis will be performed to assess efficacy after 10 patients become evaluable. The study began enrolling patients in December 2021 and is ongoing. Clinical trial information: NCT04616547.
CCTG PR21: A randomized phase II study of [177lu]lu-PSMA-617 verus docetaxel in patients with metastatic castration-resistant prostate cancer and PSMA-positive disease (NCT04663997).
Authors: Chi Kim N. , Saad Fred , Parulekar Wendy R. , Emmenegger Urban , Hotte Sebastien J. , Pouliot Frederic , Bauman Glenn , Zukotynski Katherine A. , Peacock Stuart , Wyatt Alexander William , Beauregard Jean-Mathieu , Lee Justin , Uribe Carlos , Dellar Conor , Ding Keyue , Benard Francois
Published: June 2022

TPS5110

Background: [177Lu]Lu-PSMA-617 improves outcome in men with metastatic, PSMA positive CRPC post androgen pathway inhibitor therapy and taxane chemotherapy compared to standard care (excluding chemotherapy, immunotherapy, radium-223 and investigational drugs; Sartor et al, NEJM 2021). The relative efficacy, adverse event experience and impact on QOL of [177Lu]Lu-PSMA-617 compared to docetaxel chemotherapy in this patient population is unknown. We hypothesize that [177Lu]Lu-PSMA-617 will improve radiographic PFS (rPFS) compared to docetaxel chemotherapy with a favourable safety and tolerability profile. Methods: CCTG PR21 is a Canadian Cancer Trials Group randomized phase II trial with a primary objective to compare rPFS between [177Lu]Lu-PSMA-617 7.4 GBq (+/- 10%) IV q 6 weekly (maximum 6 cycles) versus docetaxel 75 mg/m2 q 3 weekly (maximum 12 cycles). Secondary objectives are to compare the two arms with respect to: 6-month PFS rate (PCWG3 and RECIST 1.1), second rPFS after crossover to the alternate therapy, time to commencement of 3rd line systemic therapy, OS, PSA decline from baseline, clinical benefit rate and adverse events. Tertiary objectives include evaluation of QOL (FACT-P and EQ5D-5L), cost effectiveness, ctDNA and radiographic based prognostic and predictive biomarkers, dosimetry based approach to measurement of [177Lu]Lu-PSMA-617 activity and creation of tissue and image biobanks. Key eligibility criteria include: mCRPC with PSMA positive disease using 18F or 68Ga radionuclide label, progression on ADT + ARPI therapy (using PSA, RECIST 1.1 or PCWG3 criteria) and adequate organ function. Statistical Design: Patients are allocated in 1:1 ratio to [177Lu]Lu-PSMA-617 or docetaxel balanced for stratification factors of ECOG PS, LDH, visceral metastases, previous docetaxel in the castration sensitive setting > 1 year prior to enrollment as well as centre. Assuming a 6-month median rPFS for the control group, the detection of a hazard ratio (HR) of 0.67 with 80% power using a 1-sided 5% level test will require accrual of 200 participants in 24 months with 12-month follow-up to trigger the primary analysis. Conduct to Date: Study activation Dec 17 2020. Enrollment as of January 31 2022: 25. The DSMC last reviewed and recommended continuation of the trial in December 2021. Clinical trial information: NCT04663997.
Trial in progress update on ENGOT-cx8/GOG-3024/innovaTV 205: Addition of a new cohort with first-line (1L) tisotumab vedotin (TV) + pembrolizumab (pembro) + carboplatin (carbo) ± bevacizumab (bev) in recurrent/metastatic cervical cancer (r/mCC).
Authors: Vergote Ignace , Mirza Mansoor Raza , Sehouli Jalid , Lorusso Domenica , Köse Fatih , Cibula David , Westermann Anneke M. , Collins Dearbhaile Catherine , Banerjee Susana N. , Oaknin Ana , Soumaoro Ibrahima , Jain Shweta , Monk Bradley J.
Published: June 2022

TPS5603

Background: Despite the use of platinum-taxane doublets ± bev in eligible patients (pts), overall survival (OS) outcomes for pts with r/mCC remain poor. With the US approval of pembro + chemotherapy ± bev in the 1L setting for r/mCC with ≥1% of programmed death ligand 1–positive cells in the tumor, an unmet need remains for pts who do not meet this threshold and for pts who progress or are intolerant to standard treatment (tx). TV is a tissue factor–directed antibody–drug conjugate that has been granted accelerated approval in the United States for the tx of adults with r/mCC with disease progression on or after chemotherapy. To develop more effective treatments, we investigated TV in combination with agents with known activity in cervical cancer. We conducted a 2-part, multicohort phase 1b/2 trial, ENGOT-cx8/GOG-3024/innovaTV 205 (NCT03786081), to evaluate TV in combination with bev, pembro, or carbo. The phase 1b dose-escalation phase of innovaTV 205 established the recommended phase 2 dose (RP2D) and the feasibility of these doublet combinations (Monk et al, IGCS 2021). Moreover, we recently reported encouraging antitumor activity from the dose-expansion cohort of TV + carbo (1L; confirmed objective response rate [ORR], 55%; median duration of response [DOR], 8.3 mo) and TV + pembro (second-line; confirmed ORR, 38%; median DOR, 13.8 mo) (Vergote et al, ESMO 2021). The current report describes the design of a new, ongoing dose expansion cohort in the innovaTV 205 study to evaluate the combinations of TV, pembro, and carbo ± bev. Methods: A new cohort has been added to the innovaTV 205 study, comprising adult pts with recurrent or stage IVB squamous, adenosquamous, or adenocarcinoma of the cervix with no prior systemic therapy and an Eastern Cooperative Oncology Group score of 0 or 1. Pts will be treated with the RP2D of TV (2.0 mg/kg) + carbo (AUC 5 mg/mL), pembro (200 mg), and bev (15 mg/kg) every 3 weeks or with TV + carbo (AUC 5 mg/mL) and pembro (200 mg). To assess the regimen’s initial tolerability, there will be a dose-limiting toxicity evaluation period that will consist of completion of 1 tx cycle of 21 days for 6 pts enrolled to receive the quadruplet combination. The primary endpoint of this dose expansion phase is confirmed ORR per RECIST v1.1; secondary endpoints include DOR, time to response, progression-free survival, OS, and safety. Enrollment is ongoing in the United States and Europe, with additional sites planned globally. Clinical trial information: NCT03786081.
Pivotal study of ofra-vec (VB-111) combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).
Authors: Penson Richard T. , Arend Rebecca Christian , Secord Angeles Alvarez , Casado Herraez Antonio , Herzog Thomas J. , Ledermann Jonathan A. , Moore Kathleen N. , Shapira-Frommer Ronnie , Tewari Krishnansu Sujata , Rachmilewitz Minei Tamar , Harats Dror , Fain Shmueli Shifra , Monk Bradley J.
Published: June 2022

TPS5606

Background: Ofranergene obadenovec (Ofra-vec, VB-111) is an anti-cancer gene based immune activator and targeted vascular disruptor. The dual mechanism of action triggers a broad antiangiogenic effect and induces of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer (PROC) demonstrated that ofra-vec in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58%, a trend for improved survival and induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a pivotal phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent PROC and may have been previously treated with up to 5 prior lines of therapy (but not >2 for PROC). Patient are randomized 1:1 to receive ofra-vec (1x1013 Viral Particles) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The dual primary endpoints are OS and PFS. A pre-planned interim analysis of CA-125 response (GCIG) performed by the DSMC met the pre-defined criteria showing that CA-125 ORR in the treatment arm was at least 10% higher than in the control arm. Study is enrolling in the US, EU, Japan and Israel, with 90% enrollment to date. Completion of accrual is anticipated in Q1 2022. Clinical trial information: NCT03398655.
Frontline therapy of anlotinib combined with carboplatin/paclitaxel and maintenance anlotinib in patients with newly diagnosed advanced ovarian cancer: A phase II, single-arm, multicenter study.
Authors: Jiang Yi , Cheng Wenjun , Gao Yingchun
Published: June 2022

TPS5607

Background: It has been reported that antiangiogenic drug combined with chemotherapy as first-line treatment, and subsequent antiangiogenic drug as maintenance therapy for ovarian cancer can achieve better clinical benefits. Anlotinib is a highly effective VEGFRs, FGFRs, PDGFRs and c-kit multi-target tyrosine kinase inhibitor which has been approved for the treatment of several solid tumors in China. This single arm, multicentric, phase II study is expected to investigate the efficacy and safety of anlotinib combined with carboplatin/paclitaxel as front-line treatment in patients with advanced ovarian cancer. Methods: Eligible patients with FIGO stage III–IV primary epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and ECOG PS 0-1 undergo primary debulking surgery or interval debulking surgery, will receive 6-8 cycles of chemotherapy (paclitaxel 175 mg/m2 + carboplatin area under the curve [AUC] 5 q3w) and anlotinib (12 mg po qd, days 1-14, 21 days per cycle, anlotinib will be omitted from the first treatment cycle to prevent delayed wound healing). Anlotinib as maintenance monotherapy will be continue until disease progression, unacceptable toxicity, or death. Patients with prior anti-angiogenic therapy and major surgical procedure within 28 days before the first date of anlotinib therapy will be excluded. This study will recruit approximately 56 patients. The primary endpoint is progression free survival. Key secondary endpoints include overall response rate, disease control rate per RECIST1.1, overall survival, safety. The study began enrolling patients in August 2021 and is ongoing. Clinical trial information: NCT04807166.
OZM-114: Phase Ib expansion study of CX-5461in patients with solid tumors and BRCA2 and/or PALB2 mutation.
Authors: Alqaisi Husam , Lheureux Stephanie , McMullen Michelle , Knox Jennifer J. , Bowering Valerie , Lee Crystal , Chinta Rishi , Aguilar Leslie , McCormick Daniel , Chang Ariel , Huang Chi-En , Koziol Kasia , Soong John , Provencher Diane M. , Rosen Lee S. , Oza Amit M.
Published: June 2022

TPS5621

Background: Pre-clinical and clinical data demonstrate that CX-5461 selectively kills HR deficient cancer cells through stabilizing G4 structures and inducing replication-dependent DNA damage. Phase 1 studies suggest CX-5461 has clinical activity and warrants further investigation in HR-deficient tumors, including those with pathogenic BRCA2 and PALB2 mutation. The recommended phase 2 dose (RP2D) requires further refinement to establish the chronic tolerable dose for further phase 2 trials, particularly regarding the incidence of ocular toxicity. The doses of 325mg/m2 and 250mg/m2 were selected for this study expansion cohorts because it is well within the efficacy range and below the first occurrence of ocular toxicity in a previous study. Methods: This is an open-label, multi-center, phase 1b study designed to determine a tolerable dose of CX-5461 in patients with ovarian, pancreatic, prostate, and breast cancers for Phase II trials. Eligible patients will be enrolled into two cohorts: A) Main cohort (target accrual: 32 patients) and B) Exploratory cohorts (target accrual: 20 patients), see table-1 below. The primary outcomes include assessment of: 1) Safety and tolerability of CX-5461, in particular to determine late onset ocular toxicity 2) Anti-tumor activity of CX-5461 in patients with solid tumors and germline BRCA2 and/or PALB2 mutation, and 3) Effect of CX-5461 on Quality of Life measures. Secondary outcomes include evaluation of :1) Safety: CTCAE v 5.0, SAEs, dose modifications due to AEs, 2) Activity: best overall response from tumor evaluations performed every 2 cycles, according to RECIST v1.1, and duration of response., and 3) patient-reported outcomes: PRO (PRO-CTCAE v1.0 questionnaires to evaluate cutaneous, gastrointestinal, visual/perceptual, cardio/circulatory, sleep/wake and miscellaneous symptoms. Exploratory Objectives include assessment of: 1) anti-tumor activity of CX-5461 in patients with ovarian cancer and pathogenic/likely-pathogenic BRCA1 mutation and/or other HRD-associated somatic mutation, and 2) molecular profile of tumors and predictive value of mutational signatures in predicting response or resistance to CX-5461. Clinical trial information: NCT04890613. [Table: see text]
TACTI-003: A randomized phase IIb study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab as first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma.
Authors: Adkins Douglas , Cheshuk Valerii , Peguero Julio Antonio , Park John J. , Lopez-Pousa Antonio , Lybaert Willem , Brana Irene , Doger Bernard , Triebel Frederic
Published: June 2022

TPS6099

Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein targeting a subset of MHC class II molecules that mediate antigen presenting cell (APC) and CD8 T-cell activation. Data from a non-randomized, phase II trial of efti plus pembrolizumab (TACTI-002) showed encouraging antitumor activity and manageable safety when given as second-line treatment of patients with recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC). TACTI-003 (NCT04811027) is a multicenter, open label, randomized phase IIb trial to investigate efti plus pembrolizumab in the first-line setting for RM-HNSCC. Methods: A total of 154 patients (pts) are currently being recruited into two cohorts (A+B). In cohort A, pts with tumors that are CPS≥1 will be randomly assigned 1:1 to receive either efti (30 mg subcutaneously Q2W for initial 6 months, thereafter Q3W) plus pembrolizumab (400 mg intravenously Q6W) for up to two years or pembrolizumab alone. Randomization will be stratified by CPS (1-19 vs. ≥ 20) and ECOG PS (0 vs. 1). Pts with tumors that are CPS < 1 will receive efti plus pembrolizumab (cohort B). Imaging will be performed every 9 weeks. The primary endpoint (EP) is objective response rate (ORR) by RECIST1.1. Secondary EPs include overall survival, ORR according to iRECIST, time to and duration of response, disease control rate, progression-free survival, occurrence of anti-efti -specific antibodies, safety, and quality of life. Exploratory endpoints comprise biomarkers. The study has been approved by relevant competent authorities, ethic committees and IRBs. Clinical trial information: NCT04811027.
Comparing an operation to monitoring, with or without endocrine therapy (COMET), for low-risk ductal carcinoma in situ (DCIS).
Authors: Lynch Thomas , Frank Elizabeth S. , Collyar Deborah E. , Pinto Donna , Basila Desiree , Partridge Ann H. , Thompson Alastair Mark , Hwang Eun-Sil Shelley , Li Fan , Ren Yi , Hyslop Terry
Published: June 2022

TPS616

Background: Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS) each year. Without treatment, it is estimated that only 20-30% of DCIS will lead to invasive breast cancer (IBC). However, over 97% of women are currently treated with surgery +/- radiation. An alternative to surgery is active monitoring (AM), a management approach in which mammograms/physical exams are used to monitor breast changes and determine when, or if, surgery is needed. The COMET Study will compare risks and benefits of AM versus surgery for low-risk DCIS in the setting of a Phase III multicenter prospective randomized trial. The study is funded by the Patient-Centered Outcomes Research Institute. The COMET trial opened in the U.S. in June 2017 (Clinicaltrials.gov reference: NCT02926911). In November 2021, the Data Safety Monitoring Board reviewed the trial and suggested that it continue as planned. Patient accrual will continue until 12/31/2022. Methods: The primary objective is to assess whether the 2-year ipsilateral IBC rate for AM is non-inferior to that for surgery. Secondary objectives include determining whether AM is non-inferior to surgery for 2-year mastectomy rate; breast conservation rate; contralateral breast cancer rate; overall and breast cancer-specific survival. Patient reported outcomes will enable comparison of health-related quality of life and psychosocial outcomes between surgery and AM groups at baseline, 6-months, and years 1-5. Eligibility criteria include: age > 40 at diagnosis; pathologic confirmation of grade I/II DCIS or atypia verging on DCIS without invasion by two pathologists; ER and/or PR ≥ 10%; no mass on physical exam or imaging. The accrual goal is 1200 randomized patients across 100 Alliance for Clinical Trials in Oncology sites. Sample size is estimated using a 2-group test of non-inferiority of proportions, with the 2-year IBC rate in the surgery group assumed to be 0.10 based on published studies and non-inferiority margin of 0.05. Based on a 1-sided un-pooled z-test, with alpha = 0.05, a sample size of n = 446 per group will have 80% power to detect the specified non-inferiority margin. Final analysis plan will include a per protocol component as well as a pragmatic component for patients who are randomized and decline participation in their assigned arm. Primary analyses will adjust for dropout, non-compliance and contamination by utilizing instrumental variable methods. Clinical trial information: NCT02926911.
Implementation of the Avera/Sema4 oncology and analytics protocol (ASAP).
Authors: Williams Casey B. , Starks David , Elsey Rachel , Meissner Tobias , Solomon Benjamin Maurice , Albano Melanie , Hantash Feras , Schadt Eric , Rojas-Espaillat Luis Alexander , Lee John H. , Oh William K.
Published: June 2022

TPS6605

Background: Precision medicine represents a new era in oncology and population health. Comprehensive molecular profiling and hereditary cancer testing are increasingly important in the routine management of many malignancies, yet may not be widely adopted in many practices and leads to patients not consistently receiving care recommended by current national guidelines such as NCCN and ASCO. In addition, available targeted DNA sequencing panels may be limited to only defined drivers and lack detection in precancerous conditions. Whole exome sequencing (WES) combined with whole transcriptome sequencing (WTS) represent an expanded testing approach that identifies additional genetic changes beyond standard commercial panel tests. Current evidence suggests that WES/WTS is feasible to carry out in routine clinical practice, with improved detection of somatic alterations compared to smaller panels, and the promise to enhance access to targeted therapies and clinical trials. The primary purpose of the ASAP study is to understand the breadth of molecular characteristics present in participants cared for in a large integrated community-based health system, by linking comprehensive molecular profiles with clinical data extracted and curated from the electronic medical record. Methods: Avera Health is a large, Midwestern, predominantly rural vertically integrated health system with six regional cancer centers and over 40 oncology outreach sites across South Dakota and surrounding states. The ASAP study was initiated in November 2021 in GYN and as of February, the study is enrolling in the Otolaryngology clinic and expected to open in medical oncology and hematology in March/April 2022. The study will expand to include additional cancer centers outside of Sioux Falls later in 2022 and is anticipated to be open for accrual for 5 years. Enrolled participants are expected to receive WES/WTS and proteomics on their primary tumor and metastatic sites were feasible as well as hereditary testing, pharmacogenomics (PGx) and microbiome profiling. Liquid biopsies will be performed every 3 months while on treatment or when treatment is changed, in follow up to coincide with scheduled radiographic testing, and as part of annual routine surveillance. For participants not diagnosed with cancer, each participant will receive hereditary testing, PGx, microbiome, and a liquid biopsy at least annually. Participants also consent to sharing their electronic health information. Future stages of this work will employ natural language processing (NLP) methods to develop algorithms to help identify opportunities to improve patient outcomes. Projected enrollment is 1000 participants in year 1, 1500 participants in year 2, and up to 3000 annually thereafter. Approximately 50 patients have consented as of February 1 2022. Clinical trial information: NCT05142033.
KEYNOTE B68: Open-label phase 2 study of the efficacy and safety of pembrolizumab administered every six weeks in patients with relapsed or refractory classical Hodgkin lymphoma or primary mediastinal B-cell lymphoma.
Authors: Armand Philippe , Pathiraja Kumudu , Chakraborty Samhita , Marinello Patricia
Published: June 2022

TPS7585

Background: Classical Hodgkin lymphoma (cHL) and primary mediastinal B-cell lymphoma (PMBCL) frequently harbor amplifications at 9p24.1, leading to overexpression of PD-L1 and PD-L2, suggesting a genetically driven vulnerability to programmed death 1 (PD-1) blockade. The PD-1 inhibitor pembrolizumab, dosed at 200 mg every 3 weeks (Q3W), demonstrated strong antitumor activity and acceptable safety that led to approvals for adult and pediatric patients with relapsed or refractory (R/R) cHL and R/R PMBCL. Efficacy, safety, and pharmacokinetic (PK) results from studies in solid tumors have since led to accelerated approval for the pembrolizumab 400 mg Q6W regimen for all indications in adults; however, further efficacy and safety data are needed for hematologic indications. The open-label, single-arm, multisite, global, phase 2 KEYNOTE-B68 study (NCT04875195) evaluates the safety, efficacy, and PK profile of pembrolizumab 400 mg Q6W in patients with R/R cHL or PMBCL. Methods: Patients must have histologically confirmed R/R cHL (cohort 1) or R/R PMBCL (cohort 2) per WHO classification and radiographically measurable disease per the Lugano 2014 classification criteria and must not have previously received treatment with anti–PD-1 therapy. Eligible patients must have failed to respond to or relapsed after receiving an autologous stem cell transplant (ASCT) or must be ineligible for ASCT and must have failed to respond or relapsed after ≥1 (cHL) or ≥2 (PMBCL) prior lines of therapy; patients with PMBCL must have received ≥1 line of therapy containing rituximab. Approximately 60 patients will be enrolled. They will receive pembrolizumab 400 mg IV Q6W for up to 18 cycles. Disease assessments will occur Q12W by investigator per the Lugano 2014 response criteria. Local radiographic assessments will be collected by computed tomography Q12W and by positron emission tomography at weeks 12 and 24 and to confirm complete response. Adverse events will be monitored and assessed by investigators throughout the study, and their severity will be graded per NCI Common Terminology Criteria for Adverse Events, version 5.0 guidelines. Patients who receive an allogeneic SCT within 2 years of the last dose of study treatment will be monitored for 18 months after SCT for events of clinical interest. The primary end point (assessed per cohort) is objective response rate by investigator per the Lugano 2014 classification criteria. Secondary end points (assessed per cohort) include duration of response by investigator assessment, characterization of the PK profile and immunogenicity for pembrolizumab 400 mg Q6W, and safety. Exploratory end points assessed per cohort include overall survival, progression-free survival per the Lugano 2014 criteria, and molecular biomarker analyses. Clinical trial information: NCT04875195.
A novel microbial-derived peptide therapeutic vaccine (EO2463) as monotherapy and in combination with lenalidomide and rituximab, for treatment of patients with indolent non-Hodgkin lymphoma (SIDNEY).
Authors: Zinzani Pier Luigi , Ansell Stephen M. , Bosch Francesc , Friedberg Jonathan W. , Marolleau Jean pierre , Arcaini Luca , Garcia-Sanz Ramón , Gopal Ajay K. , Grande Carlos , Merryman Reid , Pinto Antonio , Smith Stephen D. , Villasboas Jose Caetano , Wallace Danielle , Fagerberg Jan , Magalhaes Joao , Armand Philippe
Published: June 2022

TPS7586

Background: EO2463 is a therapeutic vaccine designed to activate existing commensal bacteria-specific memory T cells that cross-react with B cell markers in order to drive anti-tumor immune activity against B-cell malignancies. The four microbial-derived, synthetically produced peptides contained in EO2463 (OMP72, OMP64, OMP65, and OMP66), correspond to cytotoxic CD8 T cell HLA-A2 restricted epitopes, and exhibit molecular mimicry with the B cell markers CD20, CD22, CD37, and CD268 (BAFF-receptor), respectively. In pre-clinical models, these peptides can generate strong immune responses and specifically stimulate cross-reactive cytotoxic CD8 T cells to recognize the chosen B cell targets. EO2463 also contains a CD4 helper peptide referred to as universal cancer peptide 2, derived from the human telomerase reverse transcriptase catalytic subunit. The present study is a first-in-human clinical trial of this microbiome-derived peptide therapeutic cancer vaccine approach in patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL). Methods: This four-cohort phase 1/2 trial will investigate EO2463 monotherapy, and combinations of EO2463/lenalidomide (EL), EO2463/rituximab (ER), and EO2463/lenalidomide/rituximab (ER2), for treatment of patients with FL and MZL. Cohort 1 is a safety lead-in dose-finding in patients with relapsed/refractory (RR) disease, with a 3-by-3 design to establish the recommended phase 2 dose (RP2D) for EO2463 monotherapy and to confirm the safety of the RP2D for combination schedules of EL, and ER2. After the recommended EO2463 monotherapy dose is established, cohorts 2, 3, and 4 will open to accrual. Cohort 2 will investigate EO2463 monotherapy in patients with newly diagnosed FL/MZL who are not in need of treatment; cohort 3 will investigate EO2463 monotherapy, followed by ER in patients with limited tumor burden who need treatment, and cohort 4 will further investigate EL, followed by ER2 in the RR setting. EO2463 will be administered SC 4 times at 2-week intervals, followed by continued booster administrations every 4 weeks for 9 (Cohorts 2 and 3) or 12 (Cohorts 1 and 4) months. Inclusion/exclusion criteria, and the design and schedule of the intense immune and safety monitoring will be presented. The safety lead-in dose-finding is currently ongoing, and no safety concerns have been observed thus far. Clinical trial information: NCT04669171.
MagnetisMM-9: An open-label, multicenter, non-randomized phase 1/2 study of elranatamab in patients with relapsed/refractory multiple myeloma.
Authors: Fonseca Rafael , Kuroda Junya , Ishida Tadao , Popat Rakesh , Huang Jeffrey S.Y. , Yver Anne , Vandendries Erik , Elmeliegy Mohamed , Ma Wei Dong , Sborov Douglas W.
Published: June 2022

TPS8068

Background: Elranatamab (PF-06863135) is a humanized bispecific antibody that targets both B cell maturation antigen (BCMA) on multiple myeloma (MM) cells and CD3 on T cells resulting in T cell- mediated cytotoxicity. In preclinical studies, elranatamab has demonstrated anti-myeloma activity and delayed disease progression. In the ongoing phase 1 MagnetisMM-1 study, elranatamab has demonstrated clinical efficacy and a manageable safety profile in patients with relapsed/refractory MM (Bahlis et al, J Clin Oncol 2021). Elranatamab maximum tolerated dose has not yet been reached. Subcutaneous (SC) elranatamab at the recommended dose of 76 mg QW on a 28-d cycle with a 2 step-up priming dose regimen administered during the first week is currently being evaluated in a phase 2 study, MagnetisMM-3 (Lesokhin et al, Blood, 2021). Methods: MagnetisMM-9 (start date: Oct 2021; estimated completion date: Apr 2025) is an open-label, multicenter, non-randomized phase 1/2 study evaluating an alternative priming regimen to further mitigate cytokine release syndrome (CRS) incidence and severity and to evaluate SC elranatamab Q2W and Q4W dosing regimens in patients with relapsed/refractory MM. In part 1 of the study, patients will receive premedications and 2 step-up priming doses on cycle 1 D1 (4 mg) and D4 (20 mg), followed by elranatamab 76 mg QW for 6 cycles, and a dose Q2W thereafter if partial response or better is achieved and maintained. In part 2, higher doses of elranatamab ( > 76 mg) at increased intervals between doses will be evaluated. The primary endpoint is grade ≥2 CRS rate during cycle 1. Secondary endpoints include dose-limiting toxicities (part 2 only), objective response rate, duration of response, progression-free survival, overall survival, minimal residual disease negativity rate, safety, and pharmacokinetics. Eligible patients should be ≥18 years of age with a MM diagnosis and measurable disease according to IMWG criteria, refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody, relapsed/refractory to their last treatment regimen, and have an ECOG performance status ≤1. Key exclusion criteria are smoldering MM, active plasma cell leukemia, amyloidosis, POEMS syndrome, stem cell transplant within 12 weeks of enrollment, active, uncontrolled bacterial, fungal, or viral infections, or any other active malignancy within 3 years prior to enrollment (except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ), or previous treatment with an anti-BCMA bispecific antibody. The study is open at centers in the USA, UK, Japan, and Taiwan. Clinical trial information: NCT05014412.
Phase III study with atezolizumab versus placebo in patients with malignant pleural mesothelioma after pleurectomy/decortication (AtezoMeso study).
Authors: Pagano Maria , Alloisio Marco , Cappuzzo Federico , Facciolo Francesco , Bironzo Paolo , Pastorino Ugo , Rea Federico , Santoro Armando , Zanelli Francesca , Alberti Giulia , Bonelli Candida , Gervasi Erika , Pinto Carmine
Published: June 2022

TPS8591

Background: Surgery for malignant pleural mesothelioma (MPM) is indicated mainly in multimodal approaches and in clinical trial settings. Different studies have shown significantly lower complication rates, lower peri-operative morbidity and mortality with pleural/decortication (P/D), with similar overall survival rates. The biology of mesothelioma shows significant heterogeneity. Surgical tumor reduction may create a host environment more amenable to immunotherapy by reducing the ratio of tumor cells versus antitumor effector T lymphocytes, reducing the quantities of intratumor and/or systemic immunosuppressive cells, and ablating tumor-derived paracrine factors that promote local recruitment of immunosuppressive cells. Encouraging clinical data emerging in the field of tumor immunotherapy have demonstrated that therapies focused on enhancing T-cell responses against cancer can result in a significant survival benefit. The AtezoMeso Study evaluates the introduction of atezolizumab-ATEZO in MPM, patients (pts) after P/D and platinum/pemetrexed perioperative therapy. Methods: This is a double-blind, placebo controlled, phase III trial, in 20 Italian centers. Main inclusion criteria are P/D without macroscopic residual and ECOG-PS 0-1. Pts who underwent to P/D without macroscopic residual disease and have received at least 4 cycles of perioperative therapy with cisplatin/carboplatin and pemetrexed, will be randomized (2:1) to receive ATEZO or placebo. Therapy will be administered at dose of 1,200 mg iv, every 21 days, for 12 months or until recurrence, unacceptable toxicity or patient/physician decision. Randomization will be done through a centralized system, using histology (epithelioid vs nonepithelioid) and stage (I vs > I) as stratification factors. Pts will be radiologically evaluated after surgical before starting therapy and then every 12 weeks for 24 months or until recurrence. Quality of life (QoL) will be evaluated with the EQ-5D questionnaire administered at baseline and every 12 weeks. Tissue tumor samples will be centrally analyzed to determinate the genomic profile using FoundationOne CDx platform. The primary endpoint is the evaluation of the atezolizumab efficacy in terms of disease free survival (DFS). Secondary endpoints include the safety and efficacy in terms of overall survivall and QoL. Assuming a median DFS equal to 9 months in placebo arm, an accrual time of 24 months and a follow-up time of 24 months, a sample size of 162 pts will allow to detect true hazard ratios of 0.62 with power 0.8, at a confidence level of 95%. At February 14th, 2022, 3 pts have been enrolled. Clinical trial information: 2020-003762-39; GOIRC-02-2019.
Assessing the predictive value of ctDNA on relapse in patients with resected stage IB-IIIA NSCLC treated with adjuvant chemotherapy plus concomitant atezolizumab followed by atezolizumab: BTCRC LUN 19-396.
Authors: Ardeshir-Larijani Fatemeh , Mohindra Nisha Anjali , Traynor Anne M. , Malhotra Jyoti , Shum Elaine , Ma Patrick C. , Hanna Nasser H.
Published: June 2022

TPS8592

Background: A standard of care treatment for most patients with stage II and III non-small cell lung cancer (NSCLC) and a PD-L1 > 1% is surgery followed by adjuvant (adj) histology-specific chemotherapy followed by 1 year of atezolizumab. The benefit of adding atezolizumab concomitantly to chemotherapy in the adj setting has not been reported. In addition, the optimal duration of adjuvant therapy is undefined. Emerging data have demonstrated the potential for ctDNA to predict clinical recurrence in patients with surgically resected lung, breast, and colon cancer. The current study explores the predictive value of ctDNA for early relapse in patients treated with adj chemotherapy plus atezolizumab. Methods: The LUN19-396 is a phase II biomarker study that enrolls pts with resected NSCLC stage IB (tumors ≥ 4cm), IIA, IIB, and select IIIA (T3N1-2, T4N0-2). The ctDNA will be assessed within 60 days post-surgery and then every 3 months up to 12 months. All pts will receive treatment with 4 cycles of Cisplatin 60-75mg/m2 + Docetaxel 60-75mg/m2 + Atezolizumab 1200mg IV on day 1 q 3w (for patients with squamous cell cancer) or Cisplatin 60-75mg/m2 + Pemetrexed 500mg/m2 + Atezolizumab 1200mg on day 1 IV q 3w (for patients with non-squamous cell), followed by up to 13 additional cycles of Atezolizumab 1200mg IV every 3w. This trial will enroll a total of 100 pts to achieve more than 80% power. The primary objective is to estimate the percentage of pts with detectable ctDNA after surgery who have clearance of ctDNA at designated time points during adjuvant therapy. The key secondary objective is to estimate the 1-year disease-free survival in pts with undetectable ctDNA after 4 cycles of adj chemotherapy plus atezolizumab who had detectable ctDNA after surgery. This trial has enrolled 17 pts as of February 8, 2022. Clinical trial information: NCT04367311.
Phase 3, randomized, placebo-controlled study of stereotactic body radiotherapy (SBRT) with or without pembrolizumab in patients with unresected stage I or II non–small cell lung cancer (NSCLC): KEYNOTE-867.
Authors: Jabbour Salma K. , Houghton Baerin , Robinson Andrew George , Quantin Xavier , Wehler Thomas , Kowalski Dariusz , Ahn Myung-Ju , Erman Mustafa , Giaccone Giuseppe , Borghaei Hossein , McLean Jessica , Xu Yan , Souza Fabricio , Pall Georg
Published: June 2022

TPS8597

Background: Anti–PD-(L)1-directed therapy following radiotherapy or following concurrent chemoradiation is associated with significantly longer PFS and OS in patients with advanced or metastatic NSCLC, including those with locally advanced inoperable tumors. KEYNOTE-867 (NCT03924869) evaluates the efficacy and safety of SBRT with or without pembrolizumab in patients with unresected stage I or II NSCLC. Methods: In this phase 3, randomized, placebo-controlled study, approximately 530 adult patients with previously untreated, unresected, histologically/cytologically confirmed stage I or II (T1 to limited T3, N0, M0) NSCLC are randomized 1:1 to receive thoracic SBRT to primary tumors for ≤2 wk (Table) and either pembrolizumab 200 mg or placebo every 3 wk for 17 cycles (approximately 1 year) or until disease recurrence, development of unacceptable AEs, SBRT not started for any reason, or study withdrawal. Randomization is stratified by disease stage (I vs II), ECOG PS (0 or 1 vs 2), geographic region (East Asia vs non-East Asia), and reason for not receiving surgery (medically inoperable vs refused surgery). Imaging assessment by blinded independent central review (BICR) occurs at 12 wk (≥10 wk after SBRT completion), followed by every 16 wk for 3 y, and then every 6 mo. Primary endpoints are event-free survival (EFS) by BICR and OS. Secondary endpoints include time to death or distant metastases and safety; exploratory endpoints are time to subsequent treatment, disease-specific survival, and time to recurrence/progression on subsequent line of therapy. AEs are monitored throughout the trial until 30 d after last dose (90 for serious AEs) and graded according to NCI CTCAE version 4.0. EFS and OS are analyzed by the nonparametric Kaplan-Meier method, treatment differences by stratified log-rank test, and hazard ratios by stratified Cox proportional hazard model with Efron's method of tie handling. Enrollment started on June 17, 2019, and is ongoing at 168 sites around the world. Clinical trial information: NCT03924869. [Table: see text]
A phase II randomized, open-labelled, multicenter study of safety and efficacy of combination brigatinib and carboplatin-pemetrexed therapy or brigatinib monotherapy as first-line treatment in patients with advanced ALK-positive non–small cell lung cancer (IFCT-2101 MASTERPROTOCOL ALK).
Authors: Duruisseaux Michaël , Swalduz Aurélie , Mazieres Julien , Barlesi Fabrice , Amour Elodie , Morin Franck , Westeel Virginie
Published: June 2022

TPS9144

Background: Second generation ALK tyrosine kinase inhibitors (ALK-TKI), including brigatinib, provide substantial therapeutic benefit in first-line treatment of ALK-positive NSCLC patients (pts) but relapse eventually occurs in all pts due to development of drug resistance, possibly caused by emergence of drug-tolerant cells (DTC). Combining chemotherapy to TKI may prevent DTC emergence in preclinical studies, and results in prolonged progression-free survival (PFS) and overall survival in EGFR-mutant NSCLC. We hypothesize that combination of second generation ALK-TKI with chemotherapy will improve clinical outcomes in advanced ALK-positive NSCLC patients. The IFCT-2101 MASTERPROTOCOL ALK trial will evaluate the efficacy and safety of brigatinib and carboplatin-pemetrexed combination in treatment-naïve metastatic ALK-positive NSCLC. Methods: The IFCT-2101 MASTERPROTOCOL ALK randomized, open-label phase II trial will enrol 110 pts in 30 French centers over 24 months. Eligible pts will have metastatic NSCLC with ALK-fusion according to local testing, be untreated for advanced disease, and have an ECOG Performance Status (PS) of 0-1 and at least one measurable lesion per RECIST 1.1. Pts with asymptomatic and stable brain metastases (BM) will be eligible. Exclusion criteria include leptomeningeal metastases. Patients will be randomized 1:1 to receive brigatinib monotherapy (Arm A) or combination brigatinib and carboplatin-pemetrexed therapy (Arm B), with PS (0 vs 1) and BM (presence vs absence) as stratification factors. Brigatinib will be administered at a dose of 90 mg QD for a 7-day lead-in period followed by 180 mg QD continuously, in 28-day cycles. In Arm B, 4 cycles of carboplatin (AUC 5) and pemetrexed (500 mg/m2) therapy every 3 weeks will be added at Day 8 of brigatinib treatment. Treatment will continue until progression, intolerable toxicity or discontinuation. The first 26 pts enrolled in Arm B will represent the population of a safety phase, during which adverse events (AE) will be closely monitored by an independent data monitoring committee. The primary endpoint is investigator-assessed 12-month PFS rate. Secondary endpoints include independently-reviewed 12-month PFS rate, overall response rate (ORR), 12-month intracranial PFS and ORR, incidence, nature and severity of AEs, and impact of ALK-fusion detection, co-mutations and clearance of circulating tumor (ct) DNA (Guardant360) on outcome. Exploratory objectives include the evaluation of early blood ctDNA decrease on patient outcome. The study is enrolling and primary completion date is March 2025. Clinical trial information: NCT05200481.