bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions of cancer patients and their caregivers regarding COVID-19 pandemic in Ethiopia.
Authors: Woldemariam Aynalem Abraha , Berbyuk Lindström Nataliya , Andersson Rune , Addissie Adamu
Published: June 2021

e24116

Background: Limited research is available about COVID 19 pandemic in Ethiopia in general and in relation to cancer care in particular. Ethiopia reported the first COVID-19 in March, 2020. The number of cases is increasing, putting much pressure on oncology care. This study examines what the Ethiopian cancer patients and their caregivers knew about COVID 19 after the initial stages of the pandemic. It also assesses the information needs, psychological experiences as well as the impact of pandemic on oncologist-patient-caregiver communication and treatment process. Methods: A cross-sectional study was conducted among 200 participants (100 cancer patients and 100 caregivers) at the initial stage of pandemic (May 1 - June 30, 2020) at Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia. Data was collected using a pre-tested, structured questionnaire to assess knowledge and perceptions on COVID-19. Ethics approval was obtained from the Ethical Review Board of TASH (04/14/2015) and the Ethical Review Board of Western Sweden (DNR 520-18). Results: The results indicate that though both cancer patients and their caregivers show a high awareness of and knowledge about COVID 19, they need more information about the risks specific to cancer patients. The respondents are also concerned about the risks of pandemic outbreak in Ethiopia and its impact on availability of cancer care treatments in the country. The respondents report experiencing psychological concerns in relation to the pandemic. The higher educated patients and caregivers report being more concerned than the lower educated respondents. Delays in appointments and therapy are the main concerns in relation to cancer care. Further, both patients and caregivers experience that the restrictions on the number of caregivers present during interactions with oncologists negatively influence communication, resulting in relatives being excluded and patients experiencing loneliness and lack of support. Conclusions: Getting a better insight into knowledge and awareness of COVID-19 among cancer patients and their caregivers is essential for managing the effects of pandemic in cancer care. To our knowledge, there was no similar study in Ethiopia. The results of the study contribute to insights into patient and caregiver awareness of COVID 19, essential for adoption of health care protective practices, providing information and managing oncologist-patient-caregiver communication.
Phase 1 expansion trial of the LSD1 inhibitor seclidemstat (SP-2577) with and without topotecan and cyclophosphamide (TC) in patients (pts) with relapsed or refractory Ewing sarcoma (ES) and select sarcomas.
Authors: Reed Damon R. , Chawla Sant P. , Setty Bhuvana , Mascarenhas Leo , Meyers Paul A. , Metts Jonathan , Harrison Douglas James , Lessnick Stephen L. , Crompton Brian D. , Loeb David , Stenehjem David D. , Wages David S. , Santiesteban Daniela Y. , Mirza Nadeem Q. , DuBois Steven G.
Published: June 2021

TPS11577

Background: Several sarcomas possess chromosomal translocations in FET family members ( FUS, EWSR1, and TAF15) responsible for cancer development. Sarcomas caused by FET family gene rearrangements include ES, desmoplastic round cell small tumors (DSRCT), myxoid liposarcoma (ML), and several others. Lysine specific demethylase 1 (LSD1) is a critical protein for sarcoma development and progression through its colocalization and/or association with several FET family oncogenic transcription factors. This suggests that pharmacologic inhibition of LSD1 may be a therapeutic strategy. Seclidemstat (SP-2577, Salarius Pharmaceuticals) is an oral, first-in-class, small molecule with reversible, noncompetitive inhibition of LSD1 (IC50: 25–50 nM). In vitro and in vivo data demonstrate seclidemstat, or analogs, modulate EWS/ETS transcriptional activity, down-regulating oncogene expression and up-regulating tumor-suppressor gene expression, leading to significant tumor growth inhibition in ES mouse xenograft studies. Seclidemstat has shown in in vitro ES cell lines near additivity efficacy when added to TC. In in vitro studies of other FET-translocated sarcomas, including ML (FUS/DDIT3 fusion) and clear cell sarcoma (EWS/ATF1 fusion), seclidemstat showed anti-proliferative activity. In an ongoing Phase 1 trial investigating single agent seclidemstat in advanced solid tumors (NCT03895684), three pts with metastatic FET-translocated sarcomas had a median progression-free survival of 5.7 months (range: 4.3–7.2) with a best response of stable disease despite having a median of 5 (range: 1–7) prior therapies. Methods: This dose expansion Phase 1 study (NCT03600649) assesses seclidemstat at 900 mg PO BID, the recommended Phase 2 dose, in two expansion cohorts: a single agent expansion in select sarcoma pts (n = 30) and a safety lead-in dose escalation and expansion (n = 24) of seclidemstat combined with TC in pts with ES. Pts must be ≥12 years old, have ECOG performance status of 0 or 1, with a life expectancy > 4 months. In the select sarcoma cohort, pts must have ML (n = 15) or other sarcomas with FET family translocations (n = 15) including DSRCT. One to 3 prior lines of therapy are allowed. In the ES combination cohort, up to 2 lines of prior therapy are allowed. Primary objective is safety/tolerability and secondary objective is efficacy. The trial is currently recruiting across 8 locations in the United States. Clinical trial information: NCT03600649.
Olanzapine or dexamethasone, with 5-HT3 receptor antagonist and NK-1 receptor antagonist, to prevent nausea and vomiting induced by cisplatin-based doublet chemotherapy: A non-inferiority, prospective, multi-centered, randomized, controlled, phase III clinical trial.
Authors: Liu Zhigang , Zhou Yuling , Yang Shuang , Feng Wei-neng , Chen Ming-Yuan , Zou Xiong , Han Guang , Tang Jie , Zou Guorong , He Yu-Xiang , Zhang Lemeng , Cui Lei , Chen Hualin , Li Guo , Jiang Shan , Gao Jin , Xiao Lin , Zhang Qun , Yi Wei , Huang Chenghui
Published: June 2021

TPS12133

Background: Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of cancer treatments, and dexamethasone offers an advantage over placebo for protection against chemotherapy-induced emesis in both acute and delayed phases. However, its side effects are diverse including moderate to severe insomnia, hyperglycemia, dyspepsia and so on, which are gathering increasing concerns. What’s more, dexamethasone is not applicable to all cancer patients. The incidence of diabetes mellitus varies in different cancer which can reach up to 55.3%, and dexamethasone might not be a proper anti-emesis choice for them. Besides, dexamethasone delivery is always on debating when patients are receiving immunotherapy. However, all anti-emesis regimen recommended in guidelines are dexamethasone based. Alternative anti-emesis regimen are required. Studies have shown that olanzapine plays an important role in treating delayed, refractory, breakthrough nausea and vomiting. Thus, we initiated this prospective, multi-center, phase III study to validate the dexamethasone-free protocol: the non-inferiority role of applying olanzapine to prevent CINV instead of dexamethasone. Methods: This clinical trial started on February 3, 2020 is being conducted in 23 centres. All patients eligible are chemotherapy naïve and plan to receive cisplatin-containing regimen. Based on a 70% complete remission rate of previous study, to demonstrate a non-inferiority margin of 10%, 548 patients are required for two arms with the consideration of 5% of drop out and lost to follow-up (80% power,α = 0.05). Study design: Enrolled patients are randomized 1:1 into 2 arms to receive olanzapine or dexamethasone combined with 5-HT3 receptor antagonist (palonosetron, granisetron or ondansetron) and NK-1 receptor antagonist (aprepitant or fosaprepitant) from the first day of chemotherapy. Olanzapine (5mg) is delivered orally per night from day 1 to day 4. Dexamethasone (12 mg) is given orally or intravenously within 30 minutes before cisplatin administrated on day 1; on day 2-4, the orally or intravenously given dose of dexamethasone is 8 mg. The primary endpoint is complete remission rate of vomiting during the whole observation period (0-120 hours from the starting of first course chemotherapy delivery). The secondary endpoints are complete remission rate of vomiting during 25-120 hours from the starting of first course chemotherapy delivery and no nausea rate during the whole observation period. Besides, side effects will be recorded according protocol. Clinical trial information: NCT04437017.
Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): An open-label, phase 2 trial.
Authors: Maeng Chi Hoon , Kim Bo-Hyung , Chon Jinmann , Kang Won Sub , Kang Kyounglan , Woo Mihye , Hong Il Ki , Lee Junhee , Lee Kil Yeon
Published: June 2021

TPS12134

Background: Cancer Cachexia (CC) is a multi-factorial process characterized by progressive weight loss, muscle mass and fat tissue wasting, and adversely affecting the quality of life and survival in patients with advanced stage of cancer. CC has a complex and multi-factorial pathophysiology, and there is no established standard treatment. Once it occurs, it is often irreversible and also difficult to suppress the its progression with any single treatment modality. We are conducting an open-label, parallel, randomized phase 2 trial to investigate the effect on preventing or alleviating cancer cachexia and safety of a multi-modal intervention including anti-inflammation, omega-3-fatty acids, nutritional supplement with counselling, physical exercise, psychiatric intervention as well as bojungikki-tang, which mediates immune-modulation and reverse inflammation-related chronic consumptive wasting condition as a complementary and alternative medicine compared to patients receiving best supportive care. Methods: Eligible criteria included patients with recurrent or metastatic gastrointestinal (gastric, colorectal and pancreaticobiliary) as well as lung cancer undergoing active palliative chemotherapy. Patients who have already developed refractory cachexia (ie, low performance status, difficult to take medications orally or visit the hospital to exercise) are excluded. Patients are randomized into experimental arm (Multi-modal intervention care: MIC) versus control arm (Conventional Palliative Care, CPC). MIC are comprised of 1) daily oral medications; ibuprofen 400 mg three times a day, omega-3-fatty acid 1 g twice a day, Bojungikki-tang 3.75g twice a day, oral nutritional supplement (HAMONILAN SOLN) 200 ml twice a day, and 2) clinical interventions; weekly physical exercise (60 minutes per visit), psychiatric assessment on every other week, and nutritional counselling total four times during the study period. CPC included basic nutritional counselling for two times provided by National Health Insurance Service, and megestrol acetate as needed (ie, anorexia ≥ Grade 2). All interventions were provided during 12 weeks per subject. Co-primary outcomes are change of total lean body mass and handgrip strength from the baseline. Secondary outcomes included change of fat mass and total body mass, lean body mass, Functional Assessment of Anorexia/Cachexia Treatment (FAACT) score, quality of life assessed by EORTC QLQ-C30, Spleen Qi Deficiency questionnaire (SQDQ), and overall survival. Total 112 patients will be assigned in the two arms (56 in each group). We have started the study in October 2020. At the time of submission, 26 patients were enrolled. Planned period of enrollment is 18 months. Clinical trial information: Clinical Research information Service, CRIS (KCT0004967). Clinical trial information: KCT0004967.
Primary care oncology model (PCOM): Implementation of a model integrating primary and oncology care for patients taking oral anticancer agents.
Authors: Mackler Emily R. , Farris Karen B. , Gatwood Katie S. , Rizvi-Toner Amna , Wallace Alex , Dashputre Ankur , Rajpurohit Abhijeet , Farley Joel , Gatwood Justin
Published: June 2021

TPS1587

Background: Non-adherence to oral anticancer agents (OAA) has been reported among 30% of individuals. Often, individuals with cancer are not just managing their new OAA but also medications to treat multiple chronic conditions (MCC). Multiple factors contribute to the extent patients on OAAs and MCC medications adhere to therapy. The objective of this study is to improve medication, symptom, and disease management of patients with hematological malignancies and MCC through care coordination between pharmacists. Methods: Design. This is a multi-center prospective single arm pilot study at two academic medical centers in Michigan and Tennessee. Subjects. Ninety participants will be recruited, 60 from site 1 and 30 from site 2. Inclusion criteria are: adults > 18 years, diagnosed with and initiating oral treatment for chronic myeloid leukemia, chronic lymphocytic leukemia, or multiple myeloma, diagnoses of at least 2 chronic conditions, where one is type 2 diabetes, hypertension, congestive heart failure, depression/anxiety, gastroesophageal reflux disease, hyperlipidemia, or chronic obstructive pulmonary disease, taking at least two chronic medications, and able to provide electronic consent. Exclusion criteria are: inability to speak English, and diagnosis of type 1 diabetes or HIV. Intervention. Participants will complete two Patient Reported Outcome Measures (PROMs) for their OAA that will be reviewed by the oncology pharmacist, with follow-up to the care team if needed. Participants will be scheduled for a Comprehensive Medication Review with a primary care pharmacist for up to two visits for their chronic medications. The intervention over 2 months, and the oncology and primary care pharmacists communicate via electronic health record about medications, symptoms, and disease control. Outcomes. The primary endpoints are (a) dose-adjusted adherence by proportion days covered (PDC) for the OAA and (b) PDC for chronic condition medications, assessed using 6 months of prescription claims. Data will be collected from patients using REDCap surveys and abstracted data will be entered into REDCap. Implementation by pharmacists and patient acceptability will be examined. Analysis. The association of OAA and chronic medication adherence (PDC) will be examined via correlation. Participant demographics,clinical characteristics, and the symptom experience from the PROM will be described. Using CMR results, medication problems, recommendations, and changes will be provided. Program implementation will be assessed and patient perceptions obtained from post-CMR interviews. A joint display for the quantitative and qualitative data for feasibility, appropriateness, and acceptability from pharmacists will be completed. Results: Screening and recruitment has begun. Clinical trial information: NCT04595851 and NCT04663100.
BrainStorm: A brain metastases research platform to tackle the challenge of central nervous system (CNS) metastases in solid tumors (Oncodistinct 006).
Authors: Kotecki Nuria , Franzoi Maria Alice B , Paesmans Marianne , Clatot Florian , Borcoman Edith , Goncalves Anthony , Barthelemy Philippe , Cheymol Claire , Delord Jean-Pierre , Gombos Andrea , Vanhaudenarde Vincent , Holbrechts Stephane , Duhoux Francois P. , Canon Jean-Luc Re , Decoster Lore , denys Hannelore , Duhem Caroline , Kindt Nadège , Awada Ahmad
Published: June 2021

TPS2066

Background: Better knowledge on the evolving epidemiology and biology of CNS metastases are key elements for the development of new treatment strategies and identification of promising therapeutic targets. A multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm was launched by the Jules Bordet Institute and the Oncodistinct network. The BrainStorm program includes mainly patients with non-CNS metastatic solid tumors with high risk of developing CNS metastases allowing to build a large database focusing on three time periods: before the diagnosis of CNS metastases (Part A), at diagnosis (Part B) and after the diagnosis of CNS metastases (Part C). Methods: Subjects with newly diagnosed non-CNS metastases or up to 24 months from diagnosis of non-CNS metastases from triple-negative and HER2-positive breast cancer, lung cancer and melanoma are eligible for part A of the program. Subjects presenting with a 1st CNS event and not yet enrolled (previously mentioned cohorts and a cohort of other tumor types) can enter directly in parts B and subsequently part C of the study. Eligible subjects are followed for 48 months for relevant clinical data, neurological examinations, quality of life, survival status, and undergo examinations and samplings (Table 1). A total of 280 subjects (40 per cohort) with a 1st CNS event will be enrolled. The main objectives of the program are to collect clinical and biological data with the aim to identify risk factors for CNS metastases development (Part A) and to better understand the biology of CNS metastases (brain and leptomeningeal –Parts B and C) aiming to discover new targets for therapy and intensify the multidisciplinary approach for the management of CNS metastases from solid tumors. The translational part of the program will evaluate among others the use of cerebrospinal fluid circulating tumor DNA (CSF-ctDNA) as a surrogate for CNS metastases in order to characterize its molecular landscape. Currently, the study is recruiting in several sites within the Oncodistinct network. The data collected will help to develop innovative multidisciplinary research projects that could be implemented in all parts of the BrainStorm program. Clinical trial information: NCT04109131. [Table: see text]
Zanidatamab, an anti-HER2 bispecific antibody, plus chemotherapy with/without tislelizumab as first-line treatment for patients with advanced HER2-positive breast cancer or gastric/gastroesophageal junction adenocarcinoma: A phase 1B/2 trial-in-progress.
Authors: Lee Keun Wook , Im Young-Hyuck , Lee Keun Seok , Cho Jae Yong , Oh Do-Youn , Chung Hyun Cheol Cheol , Chao Yee , Bai Li-Yuan , Yen Chia Jui , Kim In-Ho , Oh Sang Cheul , Lin Chia-Chi , Wang Jin , Wang Xin , Li Huiyan , Chen Yen-Yang , Kang Yoon-Koo
Published: June 2021

TPS2656

Background: Zanidatamab is a novel HER2-targeted antibody that binds two distinct extracellular domains of HER2, allowing for multiple mechanisms of action including enhanced binding, clustering, receptor internalization and downregulation; this results in inhibition of ligand-dependent and -independent proliferation and potent activation of antibody-dependent cellular cytotoxicity. Zanidatamab monotherapy is well tolerated and has shown promising anti-tumor activity in patients (pts) with pre-treated advanced HER2-positive cancers, and was well tolerated in a Phase I trial (NCT02892123). Tislelizumab is an investigational anti-programmed death-1 (PD-1) antibody engineered to minimize binding of FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, which is a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy. Tislelizumab is well tolerated and has anti-tumor activity alone and in combination with chemotherapy in pts with advanced solid tumors. The highly immunogenic nature of HER2 tumors has led to the development of therapies combining anti-HER2 therapies with immune checkpoint blockade. Methods: This open-label, two cohort Phase 1B/2 study (NCT04276493) is designed to evaluate zanidatamab as a first-line therapy with chemotherapy in pts with HER2-positive metastatic breast cancer (mBC; cohort 1) or with chemotherapy + tislelizumab in pts with HER2-positive advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC; cohort 2). Weight-based dosing (cohorts 1a and 2a) and flat dosing (cohorts 1b and 2b) regimens of zanidatamab are being investigated. In cohort 1 (n = 20), pts with treatment-naïve HER2-positive (IHC3+ or ISH amplified) mBC will receive intravenous (IV) zanidatamab 30 mg/kg (cohort 1a) or 1800 mg (cohort 1b), plus IV docetaxel 75 mg/m2 once every 3 weeks (Q3W). In cohort 2 (n = 30), treatment-naïve pts with HER2-positive (IHC3+ or IHC2+ with ISH amplification) advanced GC/GEJC will receive IV zanidatamab 30 mg/kg (cohort 2a), or 1800 mg (pts < 70kg; cohort 2b) or 2400 mg (pts ≥ 70kg; cohort 2b), plus IV tislelizumab 200 mg and chemotherapy (CAPOX regimen: oral capecitabine 1000 mg/m2 twice daily [days 1–14] and IV oxaliplatin 130 mg/m2 [day 1]) Q3W. For cohort 2 there is a six pt safety lead-in phase, followed by dose expansion after approval by the safety monitoring committee. Primary endpoints are the safety profile and objective response rate. Secondary endpoints include duration of response, time to response, progression-free survival, disease control rate, and overall survival. Clinical trial information: NCT02892123.
SGNTGT-001: A phase 1 study of SEA-TGT, an effector-function enhanced monoclonal antibody (mAb), in advanced malignancies (trial in progress).
Authors: Garralda Elena , Sanborn Rachel E. , Minchom Anna Rachel , Davar Diwakar , Curigliano Giuseppe , Ribrag Vincent , Mehta Amitkumar , Foss Francine M. , Zain Jasmine M. , Forero-Torres Andres , Ansell Stephen M.
Published: June 2021

TPS2657

Background: T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor expressed on subsets of T cells and NK cells. SEA-TGT is an effector-function enhanced human mAb that targets TIGIT with pico-molar affinity and blocks TIGIT’s interaction with CD155 and CD112. SEA-TGT was developed to have amplified binding to and engagement of Fcγ receptors. Enhanced effector function increases TIGIT+ T-regulatory cell depletion, enhances innate immune cell activation, and augments naïve and memory CD8+ T-cell responses. Preclinically, SEA-TGT elicits superior anti-tumor immune responses compared to other TIGIT mAbs without effector-enhanced backbones, with curative anti-tumor activity as monotherapy and in combination with other immune-modulators. Methods: This phase 1, open-label, multicenter, dose-escalation/expansion study (NCT04254107) is assessing the safety, tolerability and preliminary activity of SEA-TGT monotherapy in up to 205 adults (≥18 years) with histologically or cytologically confirmed relapsed, refractory, or progressive metastatic solid tumors (non-small cell lung, gastric/GE junction carcinomas, cutaneous melanoma, head and neck squamous cell carcinoma, bladder cancer, ovarian cancer or triple-negative breast cancer) or lymphomas (classical Hodgkin lymphoma, diffuse large B-cell lymphoma, or peripheral T-cell lymphoma, not otherwise specified). SEA-TGT will be infused on Day 1 of 21-day cycles. In Part A, the safety and tolerability of SEA-TGT will be assessed in ̃25 subjects to identify the maximum tolerated dose and recommended phase II dose (RP2D). In Part B, the safety and antitumor activity of the RP2D will be assessed in ̃180 subjects in disease-specific expansion cohorts. Primary endpoints are adverse events, laboratory abnormalities, dose-limiting toxicities, and dose-level safety and activity. Secondary endpoints are objective response (OR) rates, duration of OR, complete response, progression-free survival, overall survival, PK, and antidrug antibodies. Exploratory biomarkers of SEA-TGT-mediated pharmacodynamic (PD) effects, PK-PD correlations, and correlative analyses of predictive and PD measurements with response, toxicity, and resistance will be explored. The study was opened April 2020 and is enrolling across sites in North America and Europe. Clinical trial information: NCT04254107.
Phase I study of adoptive immunotherapy for advanced MUC1* positive breast cancer with autologous T cells engineered to express a chimeric antigen receptor, huMNC2-CAR44 specific for a cleaved form of MUC1 (MUC1*).
Authors: Specht Jennifer M. , Maloney David G. , Yeung Cecilia , Wu Vicky , Bamdad Cynthia
Published: June 2021

TPS2663

Background: Chimeric antigen receptor (CAR) T cell therapy targeting CD19 results in marked tumor regression for patients with CD19+ malignancies. It would be ideal to extend the success of CAR-T cell therapy to epithelial cancers. MUC1* is a post-translationally modified/cleaved form of mucin 1 (MUC1) that is frequently expressed on breast tumors, functions as a growth factor receptor, and a promising antigen for CAR-T cell therapy. Minerva Biotechnologies developed a CAR (huMNC2-CAR44) which recognizes MUC1* and does not bind to full-length or MUC1* negative cells. huMNC2-CAR44 product consists of autologous T cells transduced with a lentiviral vector encoding humanized MNC2-scFv (MUC1* targeting head), sequences from CD8 𝛼 leader, hinge and transmembrane domains, 4-1BB and CD3ζ domains. Methods: NCT04020575 is a phase I study evaluating the safety of adoptively transferred autologous T cells genetically modified to express huMNC2-CAR44 in patients with metastatic MUC1* positive breast cancer. After screening, leukapheresis is performed, CD8+ and CD4+ T cells are selected, transduced with huMNC2-CAR44, expanded, and antigen stimulated in vitro. Lymphodepletion with cyclophosphamide and fludarabine is followed by infusion of huMNC2-CAR44 CAR-T cells in escalating doses (3.3 x 105 CAR+ T cells/kg – 1 x 107 CAR+ T cells/kg). Key inclusion criteria include metastatic breast cancer of known ER, PR and HER2 status, MUC1* membrane expression > or = 30% with 2+ staining by IHC, measurable or evaluable disease, receipt of standard systemic therapies known to confer benefit, age > 18, informed consent, adequate organ function, and KPS > or = 60%. Patients with active autoimmune disease, uncontrolled infection, anticipated survival < 3 months, and/or untreated CNS metastases are not eligible. The primary objective is to identify the maximum tolerated (MTD) dose of huMNC2-CAR44 T cells by CTCAE v5 and Lee criteria. Secondary objectives include persistence and phenotype of adoptively transferred huMNC2-CAR44 T cells and preliminary antitumor activity. Exploratory objectives include trafficking of huMNC2-CAR44 T cells to tumor sites, effector function of huMNC2-CAR44 T cells in vivo, association between tumor MUC1* expression and huMNC2-CAR44 T cell persistence and response, change in tumor immune microenvironment by multiplex IHC in pre- and post-treatment tumor biopsies. Dose escalation is completed using a "3+3" design. Once the MTD has been determined, up to 15 more patients will be enrolled in each of 3 expansion cohorts (Luminal, HER2 positive, and TNBC) to inform future huMNC2-CAR44 T cell trials. Study is open to screening and enrollment in dose escalation. Up to 69 patients may be enrolled in dose escalation and expansion phases. Clinical trial information: NCT04020575.
A phase 1 study of RTX-321, an engineered red blood cell as an artificial antigen-presenting cell expressing HLA-A*02 with the HPV-16 E7 peptide and 4-1BB ligand with membrane-bound IL-12 for the treatment of HPV 16-positive cancers.
Authors: Bendell Johanna C. , Spira Alexander I. , Eskander Ramez Nassef , Cohen Ezra E.W. , Kuesters Geoffrey , Plescia Christopher , Campbell Karen , Chen Tiffany , Hamid Omid
Published: June 2021

TPS2664

Background: High-risk strains of HPV (HPV 16/18) have been associated with the development of multiple cancers, and the associated viral antigens are validated targets from immunotherapy approaches. We engineered red blood cells into allogeneic, off-the-shelf, artificial antigen-presenting cells (aAPCs) that express a human papillomavirus (HPV) 16 E7 peptide bound to human leukocyte antigen (HLA)-A*02:01, the costimulatory molecule 4-1BB ligand (L), and the cytokine interleukin (IL)-12 on the cell surface. This aAPC, RTX-321, activated HPV specific T-cells and promoted effector function in vitro. In animal models using a murine surrogate system, this aAPC approach resulted in robust antigen-specific T-cell expansion, NK cell expansion, tumor control, memory formation and antigen spreading, which led to a broad and robust antitumor immune response . The presence of 4-1BBL and IL-12 induced minimal toxicities in these models due to restriction of the biodistribution of the aAPC to the vasculature and spleen. RTX-321 is a potential in vivo cellular immunotherapy for treating HPV 16-positive cancers including cervical, head and neck and anal cancers. Methods: The RTX-321-01 study is a phase 1 multi-center, dose-escalation study of RTX-321 administered intravenously every 3 weeks in HLA-A*02:01-positive patients with relapsed or refractory HPV 16-positive cancers of the cervix or anal canal, or squamous cell cancers of the head and neck (HNSCC). Patients with cervical cancer or HNSCC will undergo testing for the presence of the HPV 16 virus or provide confirmation from archival tumor tissue prior to enrollment. Patients with anal cancer will not be required to have prospective determination of HPV 16-positive status prior to enrollment given the high incidence in this indication (approximately 80-85 percent of anal cancers). Approximately 18 patients will be enrolled across dose level cohorts to identify the recommended phase 2 dose (RP2D) of RTX-321, followed by RP2D expansion cohorts in specific indications. The starting dose is 1 billion (1x109) cells administered intravenously every 3 weeks (Q3W) and the dose will escalate by half-log increments, following a Bayesian logarithmic regression model (BLRM) with overdose control. Translational studies will investigate the activation and expansion of HPV16 E7 antigen-specific responses as well as broad innate and adaptive responses in multiple peripheral blood samples over the first 3 cycles of therapy as well as in optional paired tumor biopsies. At this time, the study is open and enrolling patients in the first dose escalation cohort (NCT04672980). Clinical trial information: NCT04672980.
Personalized DNA neoantigen vaccine in combination with plasmid IL-12 and pembrolizumab for the treatment of patients with advanced hepatocellular carcinoma.
Authors: Yarchoan Mark , Gane Edward , Marron Thomas Urban , Rochestie Sarah , Cooch Neil , Peters Joann , Csiki Ildiko , Perales-Puchalt Alfredo , Sardesai Niranjan
Published: June 2021

TPS2680

Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death. Immune checkpoint inhibitors targeting PD-1 have limited activity in HCC as monotherapy, with response rates ranging from 14-17%. Tumor neoantigens derived from tumor-specific mutations can be incorporated into personalized therapeutic cancer vaccines to prime T cell responses, potentially enhancing responses to anti-PD1 therapy. DNA vaccines have been shown to elicit strong CD8 and CD4 T cell responses in preclinical and clinical trials. In preclinical studies, DNA-encoded neoantigen vaccines have shown induction of CD8 T cells against 50% of predicted high affinity epitopes with the ability to impact tumor growth. GNOS-PV02 is a personalized DNA vaccine, encoding up to 40 patient-specific neoantigens. In the GT-30 trial, it is used in combination with INO-9012 (plasmid-encoded IL-12) and pembrolizumab for the treatment of advanced HCC. Methods: The GT-30 trial (NCT04251117) is a single-arm phase I/II clinical trial to assess the safety, immunogenicity, and preliminary efficacy of GNOS-PV02 in combination with INO-9012 and pembrolizumab in patients with advanced HCC. Twenty-four patients are anticipated to be enrolled. Patients are recruited upon diagnosis or during first-line treatment with tyrosine kinase inhibitors (TKI). Tumors are biopsied for exome and transcriptome sequencing. The tumor specific vaccine is designed, optimized and manufactured during first-line therapy. Each vaccine encodes up to 40 neoantigens, which includes all detected neoantigens for the majority of HCC patients. After progression or intolerance with first-line therapy, patients can commence trial therapy with concurrent personalized vaccine and pembrolizumab. GNOS-PV02 + INO-9012 are administered Q3w for the first 4 doses and Q9w thereafter until disease progression. Pembrolizumab is delivered Q3w until disease progression. Immunogenicity of each of the vaccine epitopes will be determined by ex vivo ELISpot and flow cytometry. Clinical activity is assessed by RECIST1.1 at baseline and every 9 weeks. Serial biopsies will be obtained at 9 weeks and upon disease progression to evaluate changes in the exome, transcriptome and changes to the tumor microenvironment. Clinical trial information: NCT04251117.
A phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with solid cancers harboring HER2 amplification (JUPITER trial).
Authors: Kudo Ryo , Kubo Toshio , Mori Yukiko , Harada Yohei , Shirota Hidekazu , Hayashi Hideyuki , Kano Masayuki , Shimizu Yasushi , Ishibashi Eri , Akita Hirotoshi , Matsubara Hisahiro , Nishihara Hiroshi , Ishioka Chikashi , Sueoka-Aragane Naoko , Muto Manabu , Toyooka Shinichi , Tateishi Ukihide , Hirakawa Akihiro , Miyake Satoshi , Ikeda Sadakatsu
Published: June 2021

TPS3141

Background: The human epidermal growth factor receptor 2 (HER2) gene amplification and mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. However, even if an actionable gene alteration is found, the incidence of HER2 amplification in these cancers is less than 5%. Despite its considerable therapeutic potential, the evidence is not yet mature enough for use as treatment in clinical practice. To address this unmet clinical need, we have designed an organ-agnostic basket trial, which covers a variety of solid cancers harboring HER2 amplification. Methods: JUPITER trial is a Japanese multicenter, single-arm, phase 2 basket study of combination therapy with trastuzumab and pertuzumab. Patients with solid cancers harboring HER2 amplification, who have progressed with standard treatment, or rare cancers for which there is no standard treatment, are eligible. Types of cancer include bile duct, urothelial, uterine, ovarian, and other solid cancers that HER2 amplification is detected by comprehensive genomic profiling using next-generation sequencing technology. Target sample size is 38. All enrolled patients receive combination therapy with trastuzumab and pertuzumab every 3 weeks until disease progression, unacceptable toxicity, death, or withdrawal of informed consent. Response assessment using RECIST version 1.1 is performed at weeks 9 and 17, followed by every 12 weeks. The primary endpoint is the objective response rate, and secondary endpoints are progression-free survival, overall survival, duration of response, and safety. In total, 40 patients were enrolled by June 2020. Data fix is scheduled in September 2021. Trial registration: jRCT2031180150 Clinical trial information: jRCT2031180150.
Phase 1 and phase 2a, first-in-human (FIH) study, of DRP-104, a broad glutamine antagonist, in adult patients with advanced solid tumors.
Authors: Johnson Melissa Lynne , Doroshow Deborah Blythe , Seiwert Tanguy Y. , Gibson Michael K. , Velcheti Vamsidhar , Lisberg Aaron Elliott , Patel Shetal Arvind , Scheffler Matthias , Lafleur Francois , Dugan Margaret Han , Sharma Sunil
Published: June 2021

TPS3149

Background: Dependence of cancer cells on glutamine has made glutaminolysis an attractive therapeutic target in cancer. Prior clinical trials evaluating glutamine analogues for the treatment of cancer were abandoned due to lack of efficacy and/or tolerability. DON (6-Diazo-5-oxo-L-norleucine) is an irreversible inhibitor of several enzymes that utilize glutamine as a metabolic substrate. In addition to direct anti-tumor efficacy, inhibition of glutamine metabolism in the tumor microenvironment has been shown to improve T-cell activation and tumor infiltration, increasing anti-tumor immune responses. As such, combining DON with an immune checkpoint inhibitor (ICI), has strong preclinical rationale. The investigational product DRP-104 (sirpiglenastat) is an inactive prodrug of DON designed to limit systemic DON exposure while targeting glutamine dependence in tumor cells. Methods: A phase 1/2a, FIH, multi-center, non-randomized, multi-cohort, open-label study of DRP-104 is currently open to accrual for patients with advanced solid tumors. This study will be conducted in 4 parts: A) Dose Escalation of IV and subQ DRP-104 (Run-In phase followed by modified Continual Reassessment Method) to define MTD/RP2D. Primary objective of dose escalation is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of DRP-104 as a single agent; B) Dose Expansion of IV and subQ DRP-104 for safety assessment while primary objective is to select and recommend phase 2 DRP-104 route of administration; C) Phase 2a at recommended MTD/RP2D of selected route of DRP-104 in 2 patient cohorts: patients with locally advanced/metastatic NSCLC with KEAP1, NFE2L2 and/or STK11 mutation and patients with unresectable or metastatic SCCHN, in order to assess the safety, tolerability and preliminary antitumor activity of DRP-104 as a single agent; D) Phase 2a at recommended MTD/RP2D of selected route of DRP-104 in combination with atezolizumab in adult patients with advanced solid tumors previously treated with an ICI, in order to assess the safety, tolerability and preliminary antitumor activity of DRP-104 in combination with atezolizumab; DRP-104 IV is infused TIW over 1 hour infusion for 2 consecutive weeks followed by 1 week off. DRP-104 subQ is administered BIW weekly. Study is currently open with 6 IV patients (Run-In Phase completed and at Dose Level 4) and 3 subQ patients at Dose Level 1 at time of submission. Clinical trial information: NCT04471415.
A randomized phase III study of immune checkpoint inhibition with chemotherapy in treatment-naive metastatic anal cancer patients: A trial of the ECOG-ACRIN cancer research group (EA2176).
Authors: Roth Marc Thomas , Catalano Paul J. , Ciombor Kristen Keon , Benson Al Bowen , Yao Xin , Yaeger Rona , Salem Mohamed E. , Morris Van K. , Henry David H. , Whisenant Jennifer G. , O'Dwyer Peter J. , Eng Cathy
Published: June 2021

TPS3614

Background: Anal cancer is growing in annual incidence globally and human papillomavirus (HPV) remains the predominant risk factor underlying its development. Due to its relative rarity, clinical trials in anal cancer have historically been difficult to conduct and treatment options for metastatic disease remain limited. Carboplatin/paclitaxel (CP) was compared to cisplatin/5-fluorouracil (historical standard of care) in a recent randomized phase II clinical trial (InterAACT; EA2133) in treatment-naïve metastatic anal cancer, finding that response rates were equivocal, but that overall survival (OS) was significantly longer in the CP arm (20 months vs 12.3 months, p = 0.014). Additionally, reduced grade 3/4 toxicities were seen in the CP arm. NCI9673, a single-arm phase II study, established safety and efficacy of nivolumab in previously-treated metastatic anal cancer. Progression-free survival (PFS) was 4.1 months (95% CI 3.0-7.9) and OS was 11.5 months (95% CI 7.1-not estimable). Multiple randomized trials in lung cancer have demonstrated efficacy of platinum-based chemotherapy combined with checkpoint inhibitors. Together these studies form the rationale behind combining CP and nivolumab in treatment-naïve metastatic anal cancer. Methods: EA2176 (NCT04444921) is the first NCTN phase III randomized clinical trial in treatment-naïve metastatic anal cancer. Stratification factors include HIV status and history of chemoradiation for curative intent. Patients will be randomized to carboplatin (AUC = 5, Day 1) plus paclitaxel (80mg/m2, Days 1, 8, 15) +/- nivolumab 240mg IV (Cycle 1 = Days 1, 15; Cycle ≥2 = Day 1, 480mg) q 28-days until disease progression or treatment intolerance. CP will be given for up to 6 cycles, while nivolumab will be continued as maintenance for up to 2 years. The primary endpoint is PFS. Secondary objectives include OS, response rate, and toxicity. Goal enrollment is 205 patients and the study continues accrual. This sample size will provide 80% power at a two-sided α of 0.05 to detect a 4.8-month improvement in PFS assuming 8 months in the control arm. Novel correlative studies include sequential quantitative tumor-derived cell-free HPV ctDNA levels (serotypes 16 and 18; Sysmex-Inostics SafeSEQ NGS assay). Correlative funding provided in part by the Farrah Fawcett Foundation and Sysmex Inostics, Inc. Clinical trial information: NCT04444921.
TGF-β and PD-L1 inhibition combined with definitive chemoradiotherapy in esophageal squamous cell carcinoma: A phase II clinical trial (NCT04595149).
Authors: Veen Linde , Hulshof Maarten C.C.M. , Jimenez Connie R. , Cuppen Edwin P.J.G. , Beerepoot Laurens V. , Creemers Geert-Jan , Fiets W. Edward , Jeene Paul M. , Lipman Djoeri , Haj Mohammad Nadia , Oppedijk Vera , Slingerland Marije , Vervenne Walter L. , Bijlsma Maarten F. , Van Laarhoven Hanneke W.M.
Published: June 2021

TPS4154

Background: Esophageal cancer is the 6th leading cause of mortality worldwide, with an overall 5-year survival rate of 10%. This is in part due to more than 50% of patients presenting with irresectable or metastatic disease. With the introduction of definitive chemoradiation, 3-year survival rates of patients with irresectable tumors have risen to up to 40% (Hulshof et al., ASCO GI Oral Presentation, 2020). However, treatment still fails in the majority of patients due to locoregional recurrences or development of metastatic disease. Recently, it has been shown that addition of TGF-β inhibition to chemoradiation may improve treatment efficacy (Steins et al., Int J Cancer, 2019). Additionally, PD-L1 inhibition has emerged as a relevant therapeutic strategy in specific patient subgroups, such as squamous cell carcinoma (Kato et al., The Lancet Oncology, 2019). In this phase II study, we will investigate the feasibility of addition of bintrafusp alfa, a bifunctional fusion protein blocking TGF-β and PD-L1, to definitive chemoradiation in patients with esophageal squamous cell carcinoma. Methods: To assess feasibility, 52 patients will receive definitive chemoradiation combined with three doses of bintrafusp alfa at week 1, 4 and 7 (Table). Feasibility is defined as ≥80% of patients completing 2 cycles of bintrafusp alfa and will be tested with a one-sample test for a binomial proportion, comparing the observed percentage to the fixed reference value of unfeasibility (62%). Secondary endpoints are toxicity, progression-free survival, overall survival and quality of life. Additionally, exploratory endpoints include development of biomarkers to predict treatment response. Eligible for inclusion are patients with surgically irresectable (T1-4a N+ M0) squamous cell carcinoma of the esophagus or gastro-esophageal junction, or patients with resectable tumors refraining from radical surgery. Patients with M1 disease solely on the basis of supraclavicular metastasis are eligible. Patients with locoregional recurrences are eligible, provided that full dose of radiation can be safely delivered. Currently, 2 of planned 52 patients have been enrolled. Clinical trial information: NCT04595149. [Table: see text]
Trial in progress: A phase 1, multicenter, open-label, dose-exploration and dose-expansion study evaluating the safety, tolerability, pharmacokinetics, and efficacy of AMG650 in subjects with advanced solid tumors.
Authors: Govindan Ramaswamy , Townsend Amanda Rose , Miller Kathy D. , Mehmi Inderjit , Kuboki Yasutoshi , Dumbrava Ecaterina Elena , Hamilton Erika P. , Vuu Irene , Rasmussen Erik , Mileshkin Linda R. , Genta Sofia , Iwata Hiroji , Adams Sylvia , Fujii Hisaki , Chawla Sant P.
Published: June 2021

TPS5600

Background: KIF18A is a mitotic kinesin motor protein that regulates chromosome positioning during cell division and is overexpressed in a subset of human cancers. TP53 mutant unstable aneuploid cancer cells with chromosomal instability (CIN) features are dependent on KIF18A motor activity to prevent lethal multipolar cell division. Preclinical data demonstrate that treatment with AMG 650; an oral, first in class, selective small molecule inhibitor of KIF18A may be safe and tolerable. We are conducting a first-in-human phase 1 study with AMG 650 in adult subjects with locally advanced or metastatic solid tumors with TP53MUT, triple negative breast cancer (TNBC), high grade serous ovarian cancer (HGSOC) or serous like endometrial cancers and other solid tumors. Methods: In this phase 1, multicentric, dose escalation and dose expansion study we evaluate the safety and tolerability of AMG 650 monotherapy in patients with advanced/metastatic solid tumors (NCT04293094). The main objective is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) based on emerging safety, efficacy, and pharmacodynamics (PD) data prior to reaching the MTD. Key inclusion criteria include the presence of measurable disease and diagnosis of advanced/metastatic triple negative breast cancer (TNBC), high-grade serous ovarian cancer (HGSOC), serous-like endometrial cancer or other solid tumors with documented TP53 mutations. In the dose expansion phase, participants with locally advanced or metastatic TNBC or HGSOC will be treated with the preliminary RP2D identified from the dose exploration part of the study. Primary endpoints include the incidence of Dose Limiting Toxicities (DLTs),Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment-related Adverse Events and the evaluation of the number of participants who experience a clinically significant change from baseline in vital signs, electrocardiogram and laboratory tests parameters. Secondary endpoints include Objective Response Rate, Duration of Response, Progression-free Survival, Clinical Benefit Rate, Time to Response, Time to Progression, Overall Survival (OS), Maximum Plasma Concentration (Cmax) of AMG 650, Time to Maximum Plasma Concentration (Tmax) of AMG 650 as well as Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval for AMG 650. Continuous monitoring of toxicity is conducted. The study began enrolling pts in March 2020 and is ongoing. For more information, please contact Amgen Medical Information: medinfo@amgen.com Clinical trial information: NCT04293094.