Citations

9520 Background: Capmatinib (INC280) has shown promising efficacy in patients (pts) with MET exon 14 ( METex14)–mutated NSCLC who were pretreated (cohort 4) or treatment (tx)-naïve (cohort 5b) in the ongoing, multicohort, phase 2 GEOMETRY mono-1 study. We report the results for pts enrolled in the expansion cohort 6 with either high-level MET amplification (gene copy number [GCN] ≥10) or METex14 mutation (any MET GCN) whose disease progressed on 1 prior line of systemic therapy. Methods: Adult pts (≥18 years), ECOG PS 0–1 who had ALK and EGFR wt, stage IIIB/IV NSCLC (any histology) received capmatinib tablets 400 mg twice daily (with or without food). Key efficacy endpoints were overall response rate (ORR) and duration of response (DOR) by blinded independent review committee (BIRC) per RECIST v1.1. Other secondary endpoints included investigator-assessed ORR, DOR, disease control rate (DCR), progression-free survival (PFS; BIRC and investigator assessment) and safety. Results: As of Jan 6, 2020, 34 NSCLC pts with METex14 mutation (n = 31) or high-level MET amplification (n = 3) were included in this analysis. Tx was ongoing for 38.2% of pts. In METex14-mutated NSCLC pts, per BIRC assessment: ORR was 48.4%, median DOR was 6.93 months (mo, not yet mature, 95% CI: 4.17–NE) and median PFS was 8.11 mo (not yet mature, 95% CI: 4.17–9.86). Investigator-assessed responses were similar to BIRC assessment (Table). Only 3 pts with high-level MET amplification were included in this cohort due to challenges in enrollment. All 3 pts had stable disease per BIRC assessment and were on treatment for 48, 85 and 97 days. Most common AEs (≥25%, all grades, N = 34) were peripheral edema (64.7%), nausea (35.3%), fatigue (29.4%), back pain (26.5%) and vomiting (26.5%). Data for pts with brain metastasis will be presented at the ASCO 2020 meeting. Conclusions: Capmatinib was confirmed to be efficacious in 2nd line, METex14-mutated NSCLC pts. This is the first cohort where capmatinib has been administered without fasting restriction and data confirm the favorable safety profile. Clinical trial information: NCT02414139 . [Table: see text]

Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).

Background The past two decades have witnessed a surge in the use of lumbar facet blocks and radiofrequency ablation (RFA) to treat low back pain (LBP), yet nearly all aspects of the procedures remain controversial. Methods After approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, letters were sent to a dozen pain societies, as well as representatives from the US Departments of Veterans Affairs and Defense. A steering committee was convened to select preliminary questions, which were revised by the full committee. Questions were assigned to 4–5 person modules, who worked with the Subcommittee Lead and Committee Chair on preliminary versions, which were sent to the full committee. We used a modified Delphi method, whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chair, who incorporated the comments and sent out revised versions until consensus was reached. Results 17 questions were selected for guideline development, with 100% consensus achieved by committee members on all topics. All societies except for one approved every recommendation, with one society dissenting on two questions (number of blocks and cut-off for a positive block before RFA), but approving the document. Specific questions that were addressed included the value of history and physical examination in selecting patients for blocks, the value of imaging in patient selection, whether conservative treatment should be used before injections, whether imaging is necessary for block performance, the diagnostic and prognostic value of medial branch blocks (MBB) and intra-articular (IA) injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for a prognostic block, how many blocks should be performed before RFA, how electrodes should be oriented, the evidence for larger lesions, whether stimulation should be used before RFA, ways to mitigate complications, if different standards should be applied to clinical practice and clinical trials and the evidence for repeating RFA (see table 12 for summary). Conclusions Lumbar medial branch RFA may provide benefit to well-selected individuals, with MBB being more predictive than IA injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of more false-negatives. Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.

Objectives Pancreatic resection is associated with postoperative morbidity and reduced quality of life (QoL). A systematic literature review was conducted to understand the patient-reported outcome measure (PROM) landscape in early-stage pancreatic cancer (PC). Methods Databases/registries (through January 24, 2019) and conference abstracts (2014–2017) were searched. Study quality was assessed using the Newcastle-Ottawa Scale/Cochrane risk-of-bias tool. Searches were for general (resectable PC, adjuvant/neoadjuvant, QoL) and supplemental studies (resectable PC, European Organisation for Research and Treatment of Cancer QoL Questionnaire [QLQ] – Pancreatic Cancer [PAN26]). Results Of 750 studies identified, 39 (general, 22; supplemental, 17) were eligible: 32 used QLQ Core 30 (C30) and/or QLQ-PAN26, and 15 used other PROMs. Baseline QLQ-C30 global health status/QoL scores in early-stage PC were similar to all-stage PC reference values but lower than all-stage–all-cancer values. The QoL declined after surgery, recovered to baseline in 3 to 6 months, and then generally stabilized. A minimally important difference (MID) of 10 was commonly used for QLQ-C30 but was not established for QLQ-PAN26. Conclusions In early-stage PC, QLQ-C30 and QLQ-PAN26 are the most commonly used PROMs. Baseline QLQ-C30 global health status/QoL scores suggested a high humanistic burden. Immediately after surgery, QoL declined but seemed stable over the longer term. The QLQ-C30 MID may elucidate the clinical impact of treatment on QoL; MID for QLQ-PAN26 needs to be established.

TPS600 Background: Pts with adv CCA have poor survival outcomes, and chemotherapy offers limited survival benefit (5-year survival rates, 5–10%; median overall survival [OS], 8–12 months). FGFR2 gene rearrangements are known to be early drivers of oncogenesis in ~15% of pts with intrahepatic (i) CCA. Futibatinib, an oral, highly selective, irreversible FGFR1-4 inhibitor has shown antitumor activity against a broad spectrum of FGFR-deregulated tumors in preclinical studies. In a previous study, futibatinib demonstrated clinical activity and tolerability in heavily pretreated pts with adv CCA harboring FGFR2 gene rearrangements. This phase 3 trial (FOENIX-CCA3) is designed to evaluate futibatinib vs gem-cis as 1L therapy for pts with adv iCCA harboring FGFR2 rearrangements. Methods: FOENIX-CCA3 is a multicenter, open-label, randomized phase 3 study that will be conducted in pts with metastatic or unresectable iCCA harboring FGFR2 rearrangements (assessed at screening by a central laboratory). Pts must have an ECOG performance status of 0 or 1 and should not have received previous systemic anticancer therapy for adv disease (adjuvant/neoadjuvant therapy ≥6 mo prior to randomization is permissible). Pts with clinically-significant alterations in calcium-phosphorus homeostasis or ectopic mineralization/calcification will be excluded. Approximately 216 pts will be randomized (1:1 ratio) to receive 20 mg futibatinib once daily until disease progression or other discontinuation criteria are met or gem-cis (on days 1 and 8 of a 21-day cycle) for 8 cycles or until disease progression, whichever occurs first. Pts will be stratified by prior surgical excision (yes vs no), geographic region, and locally adv vs metastatic disease. The primary endpoint is progression-free survival (PFS) assessed by independent central review (ICR). Secondary endpoints include objective response rate and disease control rate based on ICR, OS, PFS per investigator assessment, and safety. The anticipated start date is in April, 2020.

Objectives Literature suggests an inconsistent, but largely inverse, association between asthma and risk of glioma, which is primarily due to methodological inconsistency in sampling frame and ascertainment of asthma. The objective of the study was to clarify the association between asthma and risk of glioma by minimising methodological biases (eg, recall and detection bias). Design A population-based case–control study. Setting General population in Olmsted County, Minnesota, USA. Participants All eligible biopsy-proven incident glioma cases (1995–2014) and two sets of controls among residents matched to age and sex (first set: community controls without glioma; second set: MRI-negative controls from the same community). Methods The predetermined asthma criteria via medical record review were applied to ascertain asthma status of cases and controls. History of asthma prior to index date was compared between glioma cases and their matched controls using conditional logistic regression models. Propensity score for asthma status was adjusted for multivariate analysis. Results We enrolled 135 glioma cases (median age at index date: 53 years) and 270 controls. Of the cases, 21 had a history of asthma (16%), compared with 36 of MRI controls (27%) (OR (95% CI) 0.48 (0.26 to 0.91), p=0.03). With MRI controls, an inverse association between asthma and risk of glioma persisted after adjusting for the propensity score for asthma status, but did not reach statistical significance probably due to the lack of statistical power (OR (95% CI) 0.48 (0.21 to 1.09); p=0.08). Based on comparison of characteristics of controls and cases, community controls seem to be more susceptible to a detection bias. Conclusions While differential detection might account for the association between asthma and risk of glioma, asthma may potentially pose a protective effect on risk of glioma. Our study results need to be replicated by a larger study.

TPS468 Background: Intrahepatic cholangiocarcinoma (iCCA) is a cancer arising from the intrahepatic bile duct. Standard treatment of unresectable, recurrent, or metastatic iCCA is with cytotoxic chemotherapy. FGFR2 gene fusions have been identified as oncogenic drivers in 10–20% of iCCA tumors, but no targeted agents have been established to date. TAS-120 is an investigational irreversible FGFR1–4 inhibitor in development as a once-daily oral treatment for iCCA. Based on initial studies in multiple tumor types expressing FGFR abnormalities, iCCA was identified as a tumor type with potential susceptibility to FGFR inhibition and high unmet need. A phase I portion of the trial with an iCCA expansion cohort demonstrated tolerability and preliminary evidence of clinical efficacy with TAS-120 as a continuous, once-daily oral treatment in patients with iCCA. The most common AEs in the phase I portion of the trial were hyperphosphatemia, a mechanism-based on-target side effect, cutaneous AEs, and gastrointestinal AEs. The phase I portion of the study is continuing to enroll, and final results are anticipated in early 2019. Based on preliminary findings, a phase II portion of the study (FOENIX-101; clinicaltrials.gov registration NCT02052778) has been initiated. Methods: The phase II portion of the trial is a global, single-arm study of TAS-120 in patients with iCCA harboring FGFR2 gene rearrangements. The study will enroll approximately 100 adult patients with locally advanced or metastatic iCCA that progressed after ≥ 1 systemic therapies and with an ECOG PS of 0 or 1. Prior systemic therapy must include gemcitabine plus platinum-based chemotherapy. Screening for FGFR2 gene rearrangements will be performed at a central laboratory. The primary endpoint is objective response rate based on RECIST v1.1. Secondary endpoints include duration of response, disease control rate, overall survival, progression-free survival, safety, and health-related quality of life. Clinical trial information: NCT02052778.

408 Background: Standard of care for CCA/GBC is C-G therapy. MAbs (ATZ, pembrolizumab) targeting PD-L1 show promise in treating CCA/GBC. Hyaluronan (HA), which may impede drug and immune cell access, is high (67%) in CCA/GBC tumors. PEGPH20 enzymatically degrades HA. HALO 110-101 (NCT03267940) evaluates safety and activity of PEG-C-G-ATZ or PEG-C-G versus C-G in CCA/GBC pts. Methods: This study comprises two parts. In Run-In (RI) six pts were enrolled in PEG-C-G arm, then six pts in PEG-C-G-ATZ arm. Eight additional pts may be enrolled for tolerability. In Expansion (EX), up to 50 pts will be enrolled for efficacy. Treatment (Tx) cycle is 21 days (d). PEGPH20 dose is 3 μg/kg on d1, eight and 15 and ATZ dose is 1200 mg (one–three hours after PEGPH20) on d1 (PEG-C-G-ATZ only). C-G is dosed at 25 mg/m2 C and 1000 mg/m2 G on d2 and nine. In C-G arm (EX only), C-G is dosed on d1 and 8. Primary endpoints are ORR (RECIST v1.1), AEs (NCI CTCAE v4.03), laboratory/safety (RI only); secondary endpoints are PK; DOR, DCR, PFS; OS, OS by PD-L1 expression; ORR and DOR (imRECIST). Results: Eighteen pts have been enrolled (nine in each arm). The mean (SD) age is 57 (12.2) yrs in PEG-C-G and 69 (8.8) yrs in PEG-C-G-ATZ. 56% were men. All pts experienced ≥ 1 AE. The most common AEs are nausea, fatigue (50% each); decreased appetite (44%); anemia, constipation (39% each); thrombocytopenia, oedema peripheral, AST increased, myalgia (33% each). To date, there has been one dose-limiting toxicity (febrile neutropenia) in the PEG-C-G arm. There have been no deaths due to AEs. Conclusions: The overall safety profile of PEGPH20 + C + G ± ATZ is acceptable and consistent with safety observed for the individual components. There were no DLTs resulting in a dose reduction of PEGPH20, which is being dosed at 3 μg/kg in the EX phase. Clinical trial information: NCT03267940. [Table: see text]

TPS543 Background: Cholangiocarcinoma (CCA) is treated with CIS and GEM (CISGEM), but prognosis is poor. Hyaluronan (HA) accumulation in solid tumors may impede drug and immune cell access. PEGPH20 targets tumors that accumulate HA (HA-high). This study (NCT03267940) plans to enroll 70 subjects to evaluate the safety and activity of PEGPH20 + programmed cell death-ligand 1 (PD-L1) agent atezolizumab, (PEGCISGEMATEZO), & PEGPH20 + CISGEM (PEGCISGEM) in HA-high subjects with CCA and gallbladder cancer. Study will comprise initial run-in and expansion portions. Primary endpoints include incidence of AEs and other laboratory/safety parameters and ORR (RECIST v1.1). Secondary endpoints include PK parameters; DOR, DCR, PFS, and ORR (RECIST v1.1 and immune-modified RECIST); and OS and OS by PD-L1 expression. Methods: ~6 HA-high subjects will be enrolled in PEGCISGEM arm run-in portion and undergo at ≥1 cycle; subsequently, 6 HA-high subjects will enter the PEGCISGEMATEZO arm. Treatment period will be 21-day cycles. In the expansion portion, ~50 HA-high subjects will be enrolled and randomized in a 2:2:1 ratio into PEGCISGEMATEZO, PEGCISGEM, and CISGEM arms. PEGPH20 is planned to be administered at 3.0 μg/kg on Days 1, 8 and 15 of all cycles in both portions. ATEZO will be administered at 1200 mg 1–3 hours after PEGPH20 on Day 1 of each 21-day cycle in the PEGCISGEMATEZO arm in both portions. In the PEGCISGEM & PEGCISGEMATEZO arms, dosing schedule for CISGEM is the same during both portions, with administration of 25 mg/m2 CIS and 1000 mg/m2 GEM on Days 2 and 9 of each cycle. In CISGEM control arm (expansion only), dosing schedule will be on Days 1 and 8 of each cycle. Treatment will continue until death, withdrawal of consent, disease progression, or unacceptable toxicity. Tumor response will be evaluated using RECIST v1.1. AEs will be graded per NCI CTCAE v4.03. Tumor samples will be tested retrospectively for PD-L1 expression. Safety data will be periodically monitored by an independent data monitoring committee. Clinical trial information: NCT03267940.