SNOW: Sitravatinib and nivolumab in oral cavity cancer (OCC) window of opportunity study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6569-6569
Author(s):  
Marc Oliva Bernal ◽  
Daniel Vilarim Araujo ◽  
Douglas Brian Chepeha ◽  
Amy Prawira ◽  
Anna Spreafico ◽  
...  
Keyword(s):  
Immune Cell ◽  
Intraoperative Complications ◽  
Clinical Stage ◽  
Standard Of Care ◽  
Response Assessment ◽  
Complete Response ◽  
Window Of Opportunity ◽  
Antitumor Effects ◽  
Post Surgery ◽  
Early Results

6569 Background: Sitravatinib (receptor TKI against TYRO3, AXL, MERTK and VEGF family of receptors) is predicted to increase M1-type tumor-associated macrophages (TAMs) and decrease MDSCs in the tumor microenvironment. SNOW is a window-of-opportunity study evaluating the immunogenic and antitumor effects of preoperative sitravatinib and nivolumab in patients (pts) with OCC. Early results demonstrated the combination was safe and active (Oliva et al, SITC 2019). Biomarker analyses and updated results are presented. Methods: Pts with untreated T2-4a, N0-2 or T1>1cm-N2 OCC are eligible. All pts receive oral sitravatinib 120mg daily from day (D) 1 up to 48h pre-surgery and 1 dose of Nivolumab 240mg on D15. Surgery planned between D23-D30. Standard of care adjuvant radiotherapy given based on clinical stage. Tumor pictures, fresh tumor biopsies, blood samples taken at baseline, D15 and pre-surgery. Tumor flow cytometry and multiplex immunofluorescence staining performed on all biopsies to study changes in immune-cell populations. Tumor whole-exome sequencing (WES) performed on baseline biopsies. Results: As of Jan 31st 2020, 10 out of 12 planned pts were enrolled. Study treatment was well-tolerated: only 1 pt had grade (G) >3 toxicity (hypertension) and 1 pt required surgery delay due to G2 thrombocytopenia. None had intraoperative complications. 1 pt had wound infection and tracheostomy bleeding 11 days post-surgery, possibly-related to study drugs. All pts had tumor reduction, 9/10 had pathological downstaging, including 1 complete response (Table). All had clear margins with no extranodal extension; none required adjuvant chemotherapy. All pts are alive with no recurrence (median follow-up= 69 weeks). Lower % of MDSCs and increased % of M1-TAMs and M1:M2 ratio trend was seen at D15 and pre-surgery, with stronger effect in major responders. Best responders (Pts S1-S2) had higher % of PD-L1+ TAMs at baseline. Tumor WES revealed an HRAS G12D mutation in pt S2 and a BLM mutation (DNA repair) in pt S6 (no downstaging). Conclusions: Pharmacodynamic analyses support the antitumor and immune effects of sitravatinib and nivolumab in OCC. Immune pathological response assessment and transcriptomics are on-going. Clinical trial information: NCT03575598 . [Table: see text]

Pathological response and survival with neoadjuvant therapy in melanoma: A pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9503-9503 ◽  
Author(s):  
Alexander M. Menzies ◽  
Elisa A. Rozeman ◽  
Rodabe Navroze Amaria ◽  
Alexander Chan Chi Huang ◽  
Richard A. Scolyer ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Clinical Stage ◽  
Complete Response ◽  
Pooled Analysis ◽  
Stage Iii ◽  
Post Surgery ◽  
Neoadjuvant Immunotherapy ◽  
Neoadjuvant Systemic Therapy ◽  
Melanoma Patients ◽  
Stage Iii Melanoma

9503 Background: Pathological complete response (pCR) to neoadjuvant systemic therapy (NST) correlates with survival, and is recognized as a path to regulatory approval in several cancers. Recent trials have reported that neoadjuvant immunotherapy (IT) and targeted therapy (TT) regimens achieve high pCR rates and impressive recurrence-free survival in stage III melanoma, however, the relationship between pCR, relapse-free (RFS) and overall survival (OS) in larger datasets of melanoma patients (pts) remains unknown. Methods: We pooled data from 6 modern NST clinical trials of anti-PD-1 based immunotherapy or BRAF/MEK targeted therapy conducted across institutions participating in the INMC. Pts with RECIST measurable, surgically resectable clinical stage III melanoma who underwent surgery were included. NST regimens included nivolumab (as monotherapy or in combination with ipilimumab), pembrolizumab or dabrafenib+trametinib. Baseline disease characteristics, treatment regimen, pCR and RFS were examined. Results: 184 pts with clinical stage III melanoma (AJCCv7: 100 IIIB, 84 IIIC) completed NST (133 IT, 51 TT) and underwent surgery. Median age was 57y (range 18-87). A pCR was observed in 41% of patients; 51 (38%) with IT and 24 (47%) with TT. Median follow-up post-surgery is 13 mo (95% CI 12-16); 10 mo with IT and 22 mo with TT. 44 (24%) pts have recurred (17 loco-regional, 21 distant, 6 both sites at first recurrence), 18 (14%) after IT and 26 (51%) after TT. 12-month RFS was improved with IT vs TT (83% vs 65%, p < 0.001). For those with pCR, 7% have recurred, 0/51 (0%) after IT, 7/17 (41%) after TT. For those without pCR, 34% have recurred, 18/82 (22%) after IT and 19/27 (70%) after TT. 12-month RFS was improved in those with pCR vs without pCR (95% vs 62%, p < 0.001), including in those with IT (100% vs 72%, p < 0.001) and TT (88% vs 43%, p < 0.001). 16 (9%) patients have died including two who had a pCR, both from TT. Conclusions: Neoadjuvant IT and TT are active regimens in resectable clinical stage III melanoma patients and are associated with high pCR rate. The ability to achieve pCR correlates with improved RFS and remarkably no patient with pCR from immunotherapy has recurred to date.

ARC-8: Phase I/Ib study to evaluate safety and tolerability of AB680 + chemotherapy + zimberelimab (AB122) in patients with treatment-naive metastatic pancreatic adenocarcinoma (mPDAC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 404-404
Author(s):  
Gulam Abbas Manji ◽  
Zev A. Wainberg ◽  
Kartik Krishnan ◽  
Nick Giafis ◽  
Akshata Udyavar ◽  
...  
Keyword(s):  
Small Molecule ◽  
Dose Escalation ◽  
Clinical Stage ◽  
Standard Of Care ◽  
Complete Response ◽  
Target Lesion ◽  
Clinical Activity ◽  
Kras Mutations ◽  
Major Pathway ◽  
Treatment Naïve

404 Background: AB680, a potent, selective small-molecule inhibitor of soluble and membrane-bound CD73, targets a major pathway of extracellular adenosine production with the aim of eliminating adenosine-mediated immunosuppression within the tumor microenvironment. In mPDAC, programmed cell death protein-1 (PD-1) axis inhibitors have limited clinical activity as monotherapies or combined with standard-of-care (SOC) chemotherapy. KRAS mutations, present in >90% of invasive PDACs, are associated with significantly elevated CD73 expression and poor clinical outcomes. Thus, mPDAC may be particularly sensitive to CD73 inhibition combined with SOC chemotherapy + anti–PD-1 antibody (zimberelimab [Zim]) treatment. Methods: ARC-8 (NCT04104672) is an ongoing phase 1b, dose escalation and expansion study in patients (pts) with treatment-naive mPDAC. In the dose escalation, AB680 (25, 50, 75, or 100 mg) is administered intravenously once every 2 weeks (Q2W) with standard doses of nab-paclitaxel/gemcitabine (NP/Gem) + Zim (240 mg) in a 3+3 design to determine the recommended dose for expansion (RDE). In the dose expansion, AB680 will be administered at the RDE with NP/Gem + Zim. Adverse events (AEs) and dose-limiting toxicities (DLTs) are recorded and graded per NCI CTCAE 5.0. AB680 pharmacokinetics, pharmacodynamics, and biomarker evaluations are also being performed throughout the study. Clinical activity is assessed every 8 weeks per RECIST v1.1. Results: As of 04SEPT2020, enrolled patients include 4 in Cohort 1 (25 mg AB680), 6 in Cohort 2 (50 mg AB680), and 3 in Cohort 3 (75 mg AB680). Initial AE profiles were similar to those observed for NP/Gem. The most common treatment-related AEs were fatigue (n=6, 43%), anemia (n=4, 29%), and neutrophil count decrease (n=4, 29%); anemia (n=2, 14%) was the most common treatment-related grade 3/4 AE. Initial pharmacodynamic data (50 mg dose) indicated excellent peripheral target coverage at AB680 trough concentrations. Best overall responses for 9 evaluable pts were 3 with partial response (1 in Cohort 1; 2 in Cohort 2), including a complete response of a target lesion, and 5 with stable disease (1 in Cohort 1; 4 in Cohort 2). One pt in Cohort 1 discontinued the study due to progressive disease. As of the cutoff date, 1 DLT (Grade 2 autoimmune hepatitis) occurred in Cohort 2; the event completely resolved with steroids and the pt was able to resume study treatment. No DLTs were reported in Cohort 3. Conclusions: Preliminary results from ARC-8 indicate that AB680, the first clinical-stage small-molecule CD73 inhibitor, in combination with SOC chemotherapy + Zim has a manageable safety profile consistent with that expected for each agent alone and demonstrates early signals of clinical activity. Dose escalation to 100 mg AB680 (Cohort 4) is ongoing to inform RDE selection. Clinical trial information: NCT04104672.

EA8185: Phase 2 study of bladder-sparing chemoradiation (chemoRT) with durvalumab in clinical stage III, node positive urothelial carcinoma (INSPIRE)—An ECOG-ACRIN and NRG Collaboration.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4590-TPS4590
Author(s):  
Monika Joshi ◽  
Se Eun Kim ◽  
Abhishek A Solanki ◽  
David Tomoaki Miyamoto ◽  
David Degraff ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Patient Population ◽  
Clinical Stage ◽  
Standard Of Care ◽  
Complete Response ◽  
Drop Out ◽  
Stage Iii ◽  
Minimization Method ◽  
Node Positive ◽  
Bladder Sparing

TPS4590 Background: Patients [pts] withlymph node positive (LN+), non-metastatic bladder cancer (BC) have a better prognosis than those with metastatic (M1) disease. However, this population is under-represented in advanced bladder trials and ineligible for bladder-sparing trials. Therefore, there have been no larger prospective trials establishing the standard of care in LN+ BC. Given the promise of immunotherapy in advanced BC and potential synergy between immunotherapy and radiation, INSPIRE was designed to determine the role of concurrent and adjuvant durvalumab (durva) in this patient population when treated with induction chemotherapy (IC) followed by concurrent chemoRT. Methods: This is a randomized phase II study that is enrolling BC pts with stage III [N1-2 M0], pure or mixed urothelial cancer. Pts must have received ≥3 cycles of IC [either before or after registration, prior to randomization] without progression. LN+ is defined as radiologically LN ≥1.0 cm in short axis, with or without biopsy prior to IC. As long as pts do not progress on induction chemotherapy, they will be randomized to chemoRT+/- durva using 5 stratification factors (Simon Pocock minimization method) a) IC prior vs. post registration b) cisplatin vs non-cisplatin regimen during RT c) LN size d) response to IC e) extent of TURBT. Pts on the chemoRT+durva arm will get chemotherapy per physician choice + IMRT + 3 x doses of Q3wk durva for 6.5-8 wks, whereas those on the control arm will get chemoRT alone. The primary end point is clinical complete response [CR], defined as no radiologically measurable disease in the LNs and negative cystoscopy and bladder biopsy 8-10 weeks post-chemoRT +/- durva. Pts on the chemoRT + durva arm who have a CR or clinical benefit ( > T0 and ≤T2 in bladder per cystoscopy, biopsy + CR/PR/SD in LN by imaging) will get adjuvant Q4wk durva for 9 doses, while those on the chemoRT arm will undergo observation. Secondary end points include OS, PFS, bladder-intact event-free survival, rate of toxicity and salvage cystectomy. This study is designed to detect an improvement of 25% in clinical CR between both arms (37.5% to 62.5%). A total accrual of 114 pts (in order to enroll 92 evaluable pts) will provide 81% power to detect this difference using a Fisher’s exact test (assuming 10% drop out + anticipating that 20% chemotherapy-naïve pts will progress post IC). We are banking blood and primary tumor tissue pre- and post-chemoRT in both groups. The study was activated in August 2020 and accrual is ongoing. INSPIRE is the first prospective study designed for only LN+ BC and will define both short-term and long-term outcomes for bladder sparing in this patient population and has the potential to define a new treatment strategy for stage III BC. Clinical trial information: NCT04216290.

PECULIAR: An open label, multicenter, single-arm, phase 2 study of neoadjuvant pembrolizumab (PEM) and epacadostat (EPA), preceding radical cystectomy (Cy), for patients (pts) with muscle-invasive urothelial bladder cancer (MIUBC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS534-TPS534 ◽  
Author(s):  
Andrea Necchi ◽  
Luigi Mariani ◽  
Andrea Anichini ◽  
Antonella Messina ◽  
Patrizia Giannatempo ◽  
...  
Keyword(s):  
Ct Scan ◽  
Immune Cell ◽  
Residual Disease ◽  
Systemic Disease ◽  
Single Agent ◽  
Pathologic Complete Response ◽  
Study Drug ◽  
Standard Of Care ◽  
Complete Response ◽  
Open Label

TPS534 Background: MIUBC is a systemic disease and > 40% of pts develop recurrence after Cy. Despite neoadjuvant chemotherapy yields Level 1 evidence, it is underutilized worldwide and a small survival improvement is deemed over Cy alone. PEM (MK-3475) is the standard-of-care for second-line metastatic UC and is being evaluated as single-agent neoadjuvant therapy for MIUBC (NCT02736266). EPA, an anti-IDO1 agent, combined with PEM, safely improved the response-rate in metastatic UC. Our hypothesis is that PEM+EPA, given neoadjuvantly, could further improve downstaging MIUBC. Methods: Pts with T2-T4a N0 UC with residual disease after transurethral resection of the bladder (TURB, surgical opinion, cystoscopy or radiological presence), regardless of cisplatin eligibility, will receive 3 cycles of PEM 200mg intravenously, q3 weekly. EPA will be orally taken at the dose of 100 mg BID, from d1 until 10 days before Cy. Cy should be performed within 3 weeks of the last PEM dose. Computed tomography (CT) scan, 18FDG-PET/CT scan, and multiparametric bladder MRI (mpMRI) will be done during screening and before Cy to stage and evaluate response. After Cy, pts will be managed according to EAU guidelines. Adjuvant anti PD-1 therapy is not allowed. PD-L1 status will be assessed on TURB specimen (Dako, clone 22C3), relying on the combined positivity score (CPS, 10% cutoff). Pathologic complete response (pT0) is the primary endpoint. All pts enrolled who receive at least 1 cycle of study drug will be includes in the ITT analysis. The H1 is pT0≥20% and H0 pT0≤10%. A 2-stage design will be used to estimate the number of pts required. Out of 90 pts overall, with the first stage of 49 pts, ≥6 pT0 will be required in the first stage, and ≥13 pT0 in the whole study population (80% power and a 2-sided test of significance at the 10% level). Correlative research on tissue/blood samples will include immune-cell profiling, cytokine assessment, gene expression analyses and next-generation sequencing (FoundationOne). Radiologic findings from mpMRI will be associated with pathologic response (EudraCT number 2017-002379-24). Clinical trial information: 2017-002379-24.

scholarly journals Recent advances in preoperative management of esophageal adenocarcinoma

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 501 ◽  
Author(s):  
Kazuto Harada ◽  
Dilsa Mizrak Kaya ◽  
Hideo Baba ◽  
Jaffer A. Ajani
Keyword(s):  
Esophageal Cancer ◽  
Esophageal Adenocarcinoma ◽  
Clinical Stage ◽  
Stage Iv ◽  
Standard Of Care ◽  
Complete Response ◽  
Preoperative Therapy ◽  
Preoperative Treatment ◽  
Surgical Specimen ◽  
Molecular Features

Esophageal cancer is an aggressive malignancy with increasing incidence, and the prognosis of patients treated by surgery alone remains dismal. Preoperative treatment can modestly prolong overall survival. Preoperative chemotherapy or chemoradiation is the standard of care for resectable esophageal cancer (greater than clinical stage I and less than clinical stage IV). One of the challenges is to predict complete response in the surgical specimen from preoperative therapy and to avoid surgery in some patients but also predict ineffectiveness of preoperative therapy if the tumor is resistant and avoid such therapies altogether. In-depth understanding of the molecular biology could lead to personalized therapy, and in the future, clinical trials designed according to molecular features are expected. Here, we summarize preoperative treatment for esophageal adenocarcinoma and their potential.

434 Updated clinical data from the melanoma expansion cohort of an ongoing Ph1/1b Study of eganelisib (formerly IPI-549) in combination with nivolumab

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A460-A460
Author(s):  
Michael Postow ◽  
Ryan Sullivan ◽  
Ezra Cohen ◽  
Martin Gutierrez ◽  
David Hong ◽  
...  
Keyword(s):  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Suppressor Cells ◽  
Response Assessment ◽  
Complete Response ◽  
Clinical Activity ◽  
Tumor Biopsy ◽  
Evaluable Population ◽  
Duration Of Response ◽  
Baseline Response

BackgroundEganelisib is a first-in-class, oral, selective PI3K-γ inhibitor. Preclinically, eganelisib reprograms macrophages/myeloid derived suppressor cells (MDSCs) from an immune-suppressive to an immune-activating phenotype and enhances efficacy of checkpoint inhibitors. Efficacy of eganelisib + nivolumab in patients with advanced melanoma resistant to immediate prior anti-PD(L)1 therapy is presented.MethodsIPI-549-01 (NCT02637531) evaluates eganelisib in advanced solid tumors, as monotherapy and in combination with nivolumab. The combination expansion dose was eganelisib 40 mg QD PO + nivolumab 240 mg Q2W IV. Combination expansion cohorts include unresectable stage III/IV melanoma patients resistant to immediate prior anti-PD(L)1 therapy. Safety, preliminary clinical activity, PK, and correlative study of blood and tumor biopsy samples were mandated.ResultsAs of June 1, 2020, 180 patients were treated with eganelisib + nivolumab including 40 with melanoma.The most common (>20% of patients) treatment-emergent adverse events in patients treated with eganelisib + nivolumab (N = 180) were fatigue (34.4%), increased AST (30.0%), increased ALT (26.7%), nausea (25.0%), pyrexia (25.0%), anemia (22.8%), decreased appetite (20.6%), and cough (20.6%). 85 (47.2%) patients experienced at least 1 treatment-emergent serious adverse event (SAE) and 19 (10.6%) had a treatment-related SAE. There was no toxicity unique to the melanoma cohort, and no treatment-related death as assessed by investigators.Preliminary data from the melanoma cohort show that in the efficacy-evaluable population which includes all patients (n=39) who had at least 1 post-baseline response assessment or discontinued treatment due to disease progression, the overall response rate (ORR, ie. CR [complete response] or PR [partial response] per RECIST v1.1) is 7.7%, the disease control rate (DCR, ie. CR, PR, or SD [stable disease]) is 35.9%, and the clinical benefit rate (CBR, ie. CR, PR, or SD of at least 24 weeks from first treatment) is 17.9%, per RECIST v1.1. For patients that received ≤ 2 lines of prior systemic therapy (n=19), the ORR is 15.8%, the DCR is 52.6%, and the CBR is 36.8%. In total, there are 3 patients with PR (duration of response 4–12 months) and 4 with SD > 6 months‘ treatment duration.Translational data evaluating blood MDSCs, cytokines, and proliferation of previously exhausted CD8 memory T-cells as well as changes in immune cell infiltrates from tumor biopsies will be presented.ConclusionsEganelisib + nivolumab demonstrates an acceptable safety profile and clinical activity in patients with melanoma who were resistant to immediate prior anti-PD(L)1 therapy. Updated clinical and translational data will be presented.Ethics ApprovalThe study was approved by WIRB, Study Number 1188591 and IRB Tracking Number: 20180297.

A study of intravesical bacillus Calmette-Guerin (BCG) in combination with ALT-803 in patients with non-muscle invasive bladder cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS545-TPS545
Author(s):  
Charles Joel Rosser ◽  
Karim Chamie ◽  
Amy Rock ◽  
Lydia Ferguson ◽  
Hing C. Wong
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Treatment Failure ◽  
Standard Of Care ◽  
Response Assessment ◽  
Complete Response ◽  
Disease Recurrence ◽  
Low Grade ◽  
High Grade ◽  
Current Standard

TPS545 Background: The current standard of care for patients with high risk NMIBC is a transurethral resection of the bladder tumor (TURBT) or biopsy followed by a 6-week induction course of intravesical BCG treatment and supplementary maintenance instillations every 3 months thereafter (Lamm 2000). While clinical response is significantly improved with BCG treatment, 50% of patients are still expected to recur within the first 12 months (Sfakianos 2014). Thus, the pursuit of novel agents to prevent progression and recurrence of NMIBC remains critical. This clinical trial evaluates the safety and efficacy of ALT-803, an IL-15 superagonist, plus BCG in BCG-naïve NMIBC patients. Methods: Patients with high-risk NMIBC (any high-grade disease, T1, or CIS) who are BCG naïve, will be randomized and enrolled into one of two study arms to be treated with either ALT-803 plus BCG or BCG alone. Patients will receive treatment via a urinary catheter in the bladder, weekly for 6 consecutive weeks during induction. A response assessment will be performed at Week 12: Patients with no disease or low-grade Ta disease will receive a maintenance course of therapy (3 weekly instillations of either ALT-803 plus BCG or BCG alone). Presence of Ta will require a TURBT procedure. Patients with presence of high-grade Ta, CIS or low-grade T1 disease will receive a re-induction course of therapy (6 weekly instillations of either ALT-803 plus BCG or BCG alone). Presence of Ta/T1 will require a TURBT procedure. Patients with high-grade T1 or greater disease (including disease progression) will be considered a treatment failure. Patients with no disease or low-grade Ta disease at months 6, 12, and 18 are eligible for maintenance treatment according to their assigned randomization. Patients with presence of disease greater than low-grade Ta will be considered a treatment failure. The primary endpoint of the study is the proportion of patients receiving ALT-803 plus BCG who are responders by Month 12 or earlier. Responders are defined as patients who experience a complete response (CIS patients) or no disease recurrence (defined as reappearance of high-risk disease). Enrollment is underway. Clinical trial information: NCT02138734.

Preliminary results from patients with urothelial carcinoma (UC) in a phase 1A/1B study of bgb-A317, an anti-PD-1 monoclonal antibody.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 445-445 ◽  
Author(s):  
Shahneen Kaur Sandhu ◽  
Andrew Graham Hill ◽  
Hui Kong Gan ◽  
Michael Friedlander ◽  
Mark Voskoboynik ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Immune Cell ◽  
Response Assessment ◽  
Median Number ◽  
Duration Of Treatment ◽  
Antitumor Effects ◽  
Multiple Tumor ◽  
Preliminary Results ◽  
Grade 3 ◽  
Tumor Types

445 Background: Monoclonal antibodies (mAb) against programmed cell death-1 (PD-1) have demonstrated antitumor activity across multiple malignancies. BGB-A317 is a humanized IgG4 mAb with high affinity and binding specificity for PD-1. Previous reports from an ongoing Phase 1A/1B study (NCT02407990) in patients with advanced solid tumors suggested that BGB-A317 was generally well tolerated and had antitumor activity in multiple tumor types. Here, we present the preliminary results from a subset of patients with UC enrolled in this study. Methods: Patients with UC received intravenous BGB-A317 at doses of 2, 5, 10 mg/kg Q2W or Q3W and 200 mg Q3W. Tumor cell (TC) and immune cell (IC) PD-L1 expression was retrospectively assessed with the VENTANA PD-L1 (SP263) assay. Safety and tolerability was assessed by monitoring adverse events (AEs) and antitumor effects were assessed by RECIST v1.1 criteria. Results: As of 8 June 2017, 15 patients with UC (median age, 72 yr [range: 39–79]) received BGB-A317 during phases 1A (n = 8) and 1B (n = 7). All patients were Caucasian and 13 patients were male; the median number of prior systemic anticancer therapies was 1 (range: 0–4). Median duration of treatment was 115 d (range: 27–476); 6 patients remain on treatment. The most common treatment-related AEs (TRAEs) were fatigue (n = 5) and rash (n = 3); grade ≥3 TRAEs included fatigue (n = 1), and hyperglycemia and type 1 diabetes mellitus (T1DM; n = 1). Serious TRAEs occurred in 2 patients (infusion-related reaction [n = 1]; hyperglycemia and T1DM [n = 1]). All patients were evaluable for response assessment. Confirmed complete and partial responses occurred in 1 and 3 patients, respectively, for a response rate of 27%; the disease control rate (CR+PR+SD) was 53%. Nine samples were available for PD-L1 evaluation. Responses were observed in 3 of 6 patients with PD-L1+ tumors (defined as ≥25% TC or IC expressing PD-L1 by IHC) while 1 in 3 patients with PD-L1– tumors responded. Conclusions: BGB-A317 was generally well tolerated in patients with UC and objective responses were observed in both PD-L1+ and PD-L1– diseases. BGB-A317 is currently being investigated in China as monotherapy for patients with PD-L1+ UC (CTR20170071). Clinical trial information: NCT02407990.

scholarly journals NIMG-16. FEASIBLITY OF FLUORINE-18 FLUCICLOVINE PET-CT AND MRI FOR MONITORING OF CHEMO-RADIATION IN GLIOBLASTOMA: INITIAL RESULTS FROM A PILOT STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi164-vi165
Author(s):  
Susan C Short ◽  
Russell Frood ◽  
David Broadbent ◽  
Sharon Fernandez ◽  
Garry McDermott ◽  
...  
Keyword(s):  
Disease Progression ◽  
Standard Of Care ◽  
Response Assessment ◽  
Early Response ◽  
Post Treatment ◽  
Residual Tumour ◽  
Post Surgery ◽  
Pet Ct ◽  
Mri Scans ◽  
Ct And Mri

Abstract BACKGROUND Glioblastoma has a poor prognosis despite treatment with surgery and chemo-radiotherapy (CRT). Monitoring early response to CRT is challenging and conventional imaging is sub-optimal for stratifying poorly responding patients for novel agents. Also, imaging is not routinely performed during CRT and consequently, personalised treatment through individualised radiation dose adaption is not possible. AIMS: To evalutate the feasibility of Fluorine-18 Fluciclovine PET-CT for early response assessment during and post-treatment in patients with glioblastoma undergoing standard-of-care CRT. METHODS Patients with confirmed glioblastoma and macroscopic residual tumour post-surgery were consented for PET-CT and MRI prior to CRT (scan 1), after completing 2 weeks (10 fractions) of CRT (scan 2) and 6 weeks after completing treatment (scan 3). For each scan, patients were immobilised in a radiotherapy treatment mask. PET-CT and MRI scans were performed at each timepoint within a few days of each other. Patients were treated and followed up according to local guidelines. RESULTS 6 patients were recruited to the study between June 2018 and May 2019. All patients tolerated the additional imaging without problems. 2 patients were unable to attend their post-treatment PET-CT scan due to clinical deterioration. Fluciclovine PET-CT highlighted potentially active disease beyond the surgical cavity pre-radiotherapy (scan 1) in 3 patients. In 4/6, PET signal persisted after 2 weeks of radiotherapy with stable MRI appearances (scan 2). Frank disease progression was seen in 1 patient on both MRI and PET-CT mid-treatment. 3/4 patients with persistent activity at scan 2, showed disease progression post-treatment on both PET-CT and MRI (scan 3). Another had progressive changes on MRI but stable PET-CT appearances possibly representing pseudoprogression. CONCLUSION These preliminary results suggest that Fluciclovine PET-CT could help in monitoring treatment and further work to assess the ability to guide individualised treatment planning in glioblastoma is warranted.

scholarly journals A Histologically Complete Response to Immunotherapy Using Pembrolizumab in a Patient with Giant Cell Carcinoma of the Lung: An Additional Report and Literature Review

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Tomoo Kakimoto ◽  
Mamoru Sasaki ◽  
Tatsuya Yamamoto ◽  
Arifumi Iwamaru ◽  
Kentaro Ogata ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Giant Cell ◽  
Lung Tumor ◽  
Clinical Stage ◽  
Sarcomatoid Carcinoma ◽  
Complete Response ◽  
Giant Cell Carcinoma ◽  
Post Surgery ◽  
Tumor Residue ◽  
Tumor Reduction

We previously reported a case of giant cell carcinoma in the lung, in which the use of antiprogrammed death 1 (PD-1) immunotherapy resulted in substantial tumor reduction. In the present study, we describe an additional clinical course. A 69-year-old woman was diagnosed with giant cell carcinoma of the lung in clinical stage IVB (T2bN0M1c, BRA). The tumor expressed programmed death ligand 1 (PD-L1) in a high proportion. The patient received stereotactic radiotherapy for two sites of small brain metastases, followed by immunotherapy using anti-PD-1 antibodies (pembrolizumab). The treatment exerted a substantial tumor reduction through four cycles. However, treatment was withdrawn due to renal dysfunction. The primary lung tumor continued to regress for an additional four months without any further therapy, resulting in a clinical stage of T1aN0M0. Salvage thoracic surgery was then performed to remove the tumor residue in the lung. Microscopic examination of the sample revealed no residual cancer. The patient was free from recurrence at 16 months post surgery. We then comprehensively reviewed lung sarcomatoid carcinoma cases in the literature, in which anti-PD-1 antibodies were implemented. The current literature and our own findings suggest sarcomatoid carcinomas express high levels of tumoral PD-L1 and can be effectively treated with anti-PD-1 antibodies.

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