Epithelial-mesenchymal transition (EMT) has been associated with metastatic spread and EGF receptor (EGFR) inhibitor resistance. We developed and validated a robust 76-gene EMT signature using gene ...expression profiles from four platforms using non-small cell lung carcinoma (NSCLC) cell lines and patients treated in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) study.
We conducted an integrated gene expression, proteomic, and drug response analysis using cell lines and tumors from patients with NSCLC. A 76-gene EMT signature was developed and validated using gene expression profiles from four microarray platforms of NSCLC cell lines and patients treated in the BATTLE study, and potential therapeutic targets associated with EMT were identified.
Compared with epithelial cells, mesenchymal cells showed significantly greater resistance to EGFR and PI3K/Akt pathway inhibitors, independent of EGFR mutation status, but more sensitivity to certain chemotherapies. Mesenchymal cells also expressed increased levels of the receptor tyrosine kinase Axl and showed a trend toward greater sensitivity to the Axl inhibitor SGI-7079, whereas the combination of SGI-7079 with erlotinib reversed erlotinib resistance in mesenchymal lines expressing Axl and in a xenograft model of mesenchymal NSCLC. In patients with NSCLC, the EMT signature predicted 8-week disease control in patients receiving erlotinib but not other therapies.
We have developed a robust EMT signature that predicts resistance to EGFR and PI3K/Akt inhibitors, highlights different patterns of drug responsiveness for epithelial and mesenchymal cells, and identifies Axl as a potential therapeutic target for overcoming EGFR inhibitor resistance associated with the mesenchymal phenotype.
We hypothesised that zanubrutinib, a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor, would be a safe and active treatment for patients intolerant of ibrutinib, acalabrutinib, ...or both. We aimed to assess whether zanubrutinib would prolong treatment duration by minimising treatment-related toxicities and discontinuations in patients with previously treated B-cell malignancies.
This ongoing, phase 2, multicentre, open-label, single-arm study was done in 20 centres in the USA. Patients aged 18 or older with previously treated B-cell malignancies (chronic lymphocytic leukaemia, small lymphocytic lymphoma, mantle cell lymphoma, Waldenström macroglobulinaemia, or marginal zone lymphoma) who became intolerant of ibrutinib, acalabrutinib, or both, were orally administered zanubrutinib 160 mg twice daily or 320 mg once daily per investigator. The primary endpoint was recurrence and change in severity of ibrutinib or acalabrutinib intolerance events based on investigator-assessed adverse events. Secondary endpoints were investigator-assessed overall response rate; duration of response; disease control rate; and progression-free survival. Analyses included all patients who received any dose of the study drug. This study is registered with ClinicalTrials.gov, NCT04116437.
Between Oct 14, 2019, and Sept 8, 2021, 67 patients (36 54% men and 31 46% women) who were intolerant of ibrutinib (n=57; cohort 1) or of acalabrutinib or acalabrutinib and ibrutinib (n=10; cohort 2) were enrolled. 63 (94%) patients were White, one (2%) had multiple ethnicities, and three (5%) had unreported or unknown ethnicity. Most intolerance events (81 70% of 115 for ibrutinib; 15 83% of 18 for acalabrutinib) did not recur with zanubrutinib. Of the recurring events, seven (21%) of 34 ibrutinib intolerance events and two (67%) of three acalabrutinib intolerance events recurred at the same severity with zanubrutinib; 27 (79%) ibrutinib intolerance events and one (33%) acalabrutinib intolerance event recurred at a lower severity with zanubrutinib. No events recurred at higher severity. No grade 4 intolerance events recurred. 64 (96%) of 67 patients had one or more adverse events with zanubrutinib; the most common adverse events were contusion (in 15 22% of 67 patients), fatigue (14 21%), myalgia (ten 15%), arthralgia (nine 13%), and diarrhoea (nine 13%). Atrial fibrillation occurred in three (4%) patients (all grade 2). Eight (12%) of 67 patients had serious adverse events (anaemia, atrial fibrillation, bronchitis, COVID-19, COVID-19 pneumonia, febrile neutropenia, salmonella gastroenteritis, transfusion reaction, trigeminal nerve disorder, and urinary tract infection). No treatment-related deaths occurred. The median follow-up time was 12·0 months (IQR 8·2-15·6). Among the 64 efficacy-evaluable patients, disease control rate was 93·8% (60; 95% CI 84·8-98·3) and overall response rate was 64·1% (41; 95% CI 51·1-75·7). The median duration of response was not reached; the 12-month event-free duration of response rate was 95·0% (95% CI 69·5-99·3). Similarly, median progression-free survival was not reached; 18-month progression-free survival was 83·8% (95% CI 62·6-93·6).
Patients intolerant of previous BTK inhibitors have limited treatment options. These results suggest that zanubrutinib, a safe and viable treatment for patients with B-cell malignancies, might fill that unmet need for those who exhibit intolerance to ibrutinib or acalabrutinib.
BeiGene.
Introduction: Atypical chronic myeloid leukemia (aCML), BCR-ABL1 negative is a rare myelodysplastic syndromes (MDS)/myeloproliferative neoplasm (MPN) for which no current standard of care exists. We ...present one of the rare presentations of aCML in an elderly patient.
Case: A 76 year old male presented to the Hematology clinic for consultation after discharge from local hospital for elevated WBC count. Past medical history was significant for COPD, acid reflux, peripheral arterial disease and hypertension. Physical exam was unremarkable. Initial labs were significant for leukocytosis of 30 k/cu mm, anemia with Hb 10 gm/dl, thrombocytosis 695,000 with neutrophilia of ANC 25,200. Peripheral blood was negative for JAK2 V617F and BCR-ABL. Peripheral blood flow cytometry showed granulocytic left shift with 1.5% myeloblasts. Bone marrow biopsy suggestive of hypercellular marrow (100%) with myeloid predominance, atypical megakaryocytes, increased ring sideroblasts (49% of NRBC), increased blasts (5%) and dysgranulopoeisis over all suggestive of Myelodyplastic Syndrome/Chronic Myeloproliferative Disorder (MDS/MPD). Cytogenetics were positive for U2AF1 positive, CSF3R T6181, CSF3R Q776 pathognomonicof atypical CML and negative for BCR-ABL, FLT3. He was considered transplant ineligible. He was started on Azacitadine and is currently receiving 2nd cycle therapy. He is also receiving darbepoeitin periodically to avoid frequent transfusions. He is currently transfusion independent.
Discussion: Increased WBC count (e.g., cutoffs of >40×109/L or 50×109/L), increased percentage of peripheral blood myeloid precursors, female sex, and older age are adverse prognostic factors for overall survival or leukemia-free survival in aCML. aCML cases lack in Philadelphia chromosome. Overall 50-65% of patients show cytogenetic abnormalities. The most frequent is +8 (25%). Other changes such as -7 and del(12p) have also been recurrently observed. Patients with aCML have an estimated median survival between 14 and 30 months. aCML tends to exhibit a more aggressive clinical course than other MDS/MPN subtypes.
No relevant conflicts of interest to declare.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Mosunetuzumab is a CD20xCD3 bispecific antibody that is approved for the intravenous (IV) treatment of patients with relapsed/refractory (R/R) follicular lymphoma (FL) who have received ...at least two prior lines of systemic therapy, and is suitable for administration in the outpatient setting. In an ongoing Phase I/II study (NCT02500407), IV mosunetuzumab induced durable responses and had a manageable safety profile in patients with heavily pre-treated R/R indolent and aggressive B-cell non-Hodgkin lymphomas (NHL) when administered as a fixed-duration treatment (Budde et al. J Clin Oncol 2022). Subcutaneous (SC) dosing was also evaluated and showed similar efficacy to IV dosing and a manageable safety profile (Budde et al. ASH 2022). MorningSun (NCT05207670) is an ongoing, open-label, multicenter, Phase II study evaluating the efficacy, safety and pharmacokinetics of SC mosunetuzumab in patients with selected B-cell NHLs, including those without prior treatment (Flinn et al. ASCO 2022). For the first time, we present initial efficacy and safety data for patients with previously untreated, low-tumor burden FL who were enrolled into MorningSun at community and academic centers in the United States. Methods: Inclusion criteria include previously untreated Grade (Gr) 1 or 2 FL, low tumor burden by GELF criteria, Ann Arbor stage III or IV disease, and ECOG performance status 0-2. Mosunetuzumab is administered without mandatory hospitalization by SC injection in 21-day cycles. In Cycle (C) 1, mosunetuzumab is given on Day (D) 1 (5mg), D8 (45mg) and D15 (45mg). In C2+, mosunetuzumab is given on D1 only (45mg). Treatment is continued for up to 17 cycles (~1 year). Patients who are in complete metabolic response (CMR) at C8 can discontinue active treatment and enter long-term follow-up. Premedication with dexamethasone (20mg) is mandatory in C1 and C2 and optional thereafter. Acetaminophen and diphenhydramine may also be given. The primary endpoint is the rate of progression-free survival at 24 months. Results: At data cut-off (March 6, 2023), 30 patients had been enrolled (19 at community centers and 11 at academic centers). Median age was 56 years. All patients had ECOG performance status 0-1, and a minority had B symptoms ( Table 1). The median duration of follow-up was 4.2 months (range: 0.2-11.1) and the median number of cycles received was 7 (range: 1-13). Among 24 patients who had at least one post-baseline tumor assessment, 23 achieved an objective response (95.8%; 95% CI: 78.9-99.9), including 20 who achieved a CMR (83.3%; 95% CI: 62.6-95.3). All responses were observed at the first post-baseline tumor assessment in C4 (median time to response: 2.6 months; 95% CI: 2.6-2.8). At cut-off, responses were ongoing in all patients who achieved CMR and 2 of 3 patients who achieved partial metabolic response. The most common adverse event (AE) was injection site reaction (53.3% of patients), all of which were Gr 1 (43.3%) or Gr 2 (10.0%). Cytokine release syndrome (CRS) occurred in 43.3%. Most patients had Gr 1 CRS ( Table 2). No Gr ≥3 CRS events or discontinuations due to CRS were reported. CRS occurred in C1 only. All CRS events resolved. Other common (>20%) AEs were headache (50.0%), nausea (30.0%), fatigue (26.7%), pyrexia (23.3%), chills (23.3%) and alanine aminotransferase increased (23.3%). Gr ≥3 AEs in ≥5% of patients were neutrophil count decreased (2 patients; 6.7%). Serious AEs (SAEs) in ≥5% were CRS (2 patients; 6.7%). No SAEs of infection were reported. AEs potentially consistent with immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2 patients (Gr 1 confusional state and Gr 1 memory impairment in one patient each); both events resolved. No mosunetuzumab-related AEs leading to discontinuation occurred and no Gr 5 (fatal) AEs were reported. Conclusions: Initial MorningSun data support that SC mosunetuzumab is active in patients with previously untreated, low-tumor burden FL. Safety data demonstrate a manageable safety profile that is consistent with that seen in patients with R/R B-cell NHLs and is supportive of outpatient administration.
Full text
Available for:
IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
Introduction:Bruton tyrosine kinase inhibitors (BTKi) have shown remarkable utility in the treatment of B-cell malignancies; yet some patients have experienced toxicities to the BTKis, ibrutinib and ...acalabrutinib, which lead to dose reduction or treatment discontinuation. Zanubrutinib is a potent and selective next-generation BTKi. BGB-3111-215 (NCT04116437) is an ongoing, phase 2 study of the safety and efficacy of zanubrutinib monotherapy in patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) who discontinued ibrutinib, acalabrutinib, or acalabrutinib and ibrutinib because of intolerance. Methods:Because the genomic profile of patients with B-cell malignancies who are intolerant to ibrutinib and/or acalabrutinib has not been extensively studied, mutations were assessed using a 106 gene-targeted next-generation sequencing panel (PredicineHEME TM, Predicine) on baseline and disease progression samples. Samples were sequenced to a median depth of >20,000 reads, with a validated sensitivity of 0.25% mutant allele frequency for all genomic regions, and 0.1% for mutational hotspots. Variant allele frequency (VAF) <0.1% for hotspot mutations and <0.25% for non-hotspot mutations were excluded from analysis; germline and CHIP mutations were also excluded from analysis. The association between gene mutations and progression-free survival (PFS, defined as time from the date of first zanubrutinib dose to date of first PD or death) was quantified by the log rank test and the hazard ratio and summarized by the Kaplan-Meier method. Results:As of June 6, 2022, baseline peripheral blood samples were collected from 71 (95.9%) of the 74 patients enrolled in the study. There were 46 patients with CLL, 11 with WM, eight with SLL, three with MCL, and three with MZL. A total of 56 patients were intolerant to ibrutinib only; 15 were intolerant to acalabrutinib or acalabrutinib and ibrutinib. At baseline, high mutation frequencies were observed in TP53, SF3B1, ATM, and NOTCH1 across disease indications ( Figure). The majority of TP53 mutations were missense mutations and located in the DNA binding domain. Nineteen different mutations were identified in ATM and were distributed across the whole gene with a majority clustered in the 3' regions encoding the FAT and PI3 kinase domains. All mutations (n=21) in SF3B1 were missense and 38% (n=8/21) of the mutations occurred at p.K700E/c.A2098G. In NOTCH1, the most common mutation (n=8/14, 57.1%) was a two base pair deletion (c.7541_7542delCT) in the PEST domain of exon 34. In patients with CLL/SLL with TP53, SF3B1, or ATM mutations at baseline, shorter progression-free survival was observed compared to patients without these mutations, suggesting that mutations in DNA damage response and RNA splicing/metabolism pathways are associated with less favorable prognosis. BTK mutations were detected in 4.2% (n=3/71) of baseline samples and in 57.1% (n=4/7) of samples available at disease progression (PD). All BTK mutations were at the C481 BTKi binding site. Two patients with baseline BTK mutations had PD and increased VAF of BTK mutants were detected for both patients at PD. A third patient died due to illness unrelated to treatment. Two patients acquired new BTKC481 mutations at PD. Conclusion: This is the first study to describe the genomic landscape of patients with B-cell malignancies who were intolerant to ibrutinib and/or acalabrutinib. Here we show that the gene mutational profile of these patients at baseline or at/after disease progression is comparable with patients with relapse/refractory disease who tolerate ibrutinib and, consistent with other studies, patients with mutations in TP53, SF3B1 or ATM genes had less favorable prognosis on BTKi. Further, intolerant patients who progressed on zanubrutinib acquired new BTK mutations and/or had an increase in the frequency of BTK mutations. These data contribute to the growing understanding of the mutational profiles of patients with B-cell malignancies, particularly those who were intolerant to BTKi, and further explores the association between mutations and response to subsequent zanubrutinib treatment. This study may provide supporting information to inform treatment guidelines for patients who become intolerant to BTKi.
Full text
Available for:
IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
Background: Bruton tyrosine kinase inhibitors (BTKis) are important tools to treat B-cell malignancies. However, duration of treatment may be limited by adverse events (AEs). Zanubrutinib (zanu) is a ...BTKi approved for mantle cell lymphoma (MCL) and is in development for other hematologic malignancies. Data from phase 3 head-to-head trials of zanu vs ibrutinib (ibr) in pts with Waldenström macroglobulinemia (WM) or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) demonstrated that pts treated with zanu showed lower rates of AEs leading to discontinuation (Blood 2020;136(18):2038-50; EHA 2021 LB1900). Preliminary results from BGB-3111-215 (NCT04116437) show that zanu was well-tolerated in pts who discontinued ibr and/or acalabrutinib (acala) treatment due to AEs (EHA 2021 EP642). Here, we report updated results from the BGB-3111-215 study with a median follow-up of 9 months.
Methods: This study is an ongoing US, phase 2, multicenter, single-arm, open-label study. The safety and efficacy of zanu monotherapy (160 mg twice daily or 320 mg once daily) were evaluated in pts with B-cell malignancies who met criteria for continued treatment after having become intolerant to prior BTKi therapy. Pts were divided into cohort 1 (pts who were intolerant to ibr only) and cohort 2 (pts who were intolerant to acala alone/and ibr). Pts with documented progressive disease (PD) on prior BTKi therapy were excluded. Efficacy and safety, including recurrence of intolerant AEs to the prior BTKi, were evaluated. AEs were assessed for severity, seriousness, and relation to zanu; as well as dose reductions, holds, or discontinuations. Response was assessed by investigators based on response criteria for their respective indications (Blood 2008;131:2745; J Clin Oncol 2012;30:2820; J Clin Oncol 2014;32:3059; Br J Haemtol 2013;160:171). Disease parameters from study entry were the baseline for response assessment. Mutational analysis was performed on pts who discontinued treatment, and data will be shared once available. To support clinical findings, kinase selectivity was assessed using Kinome profiling at 100X IC50 (against BTK) for zanu, ibr, acala and its major metabolite, M27 (Reaction Biology Corp).
Results: As of 7 June 2021 (data cutoff), 57 pts (n=44 CLL/SLL; n=9 WM; n=2 MCL; n=2 marginal zone lymphoma MZL) were enrolled in cohort 1, and 7 pts were enrolled in cohort 2 (n=4 CLL; n=1 WM; n=1 MCL; n=1 MZL). All received ≥1 dose of zanu and were analyzed for safety. The median age was 71 years (range, 49-91) in cohort 1 and 71 years (range, 65-76) in cohort 2; median duration of treatment was 8.7 months (range, 0.6-17.9) in cohort 1 and 8.2 months (range, 6.4-11.4) in cohort 2; median number of prior regimens was 1 (range, 1-12) in cohort 1 and 3 (range, 2-5) in cohort 2. Within cohort 2, 5 pts were intolerant to both ibr and acala. Median number of intolerant events per pt for both cohorts 1 and 2 was 2 (range, 1-5). Overall, 73% of pts did not experience recurrence of their ibr or acala intolerant events and 79% of recurrent events recurred at a lower severity (Figure 1). At cutoff, 54 pts remained on treatment. Reasons for treatment discontinuation were AEs (n=4), PD (n=4), physician's decision (n=1), and consent withdrawal (n=1). Grade ≥3 AEs were reported in 18 pts (28%), and serious AEs occurred in 7 pts (11%). AEs requiring dose interruptions occurred in 17 pts (27%), and AEs leading to dose reduction occurred in 3 pts (5%). One death, due to COVID-19, was reported. Pts demonstrated maintained (41%) and improved (53%) response with zanu treatment from their reported best overall response on prior BTKis for a total disease control rate of 94% (including a 42% partial response rate in pts with CLL/SLL, 30% in pts with WM, and a 20% very good partial response rate in pts with WM). Zanu also demonstrated good selectivity by kinase profiling. It showed >50% inhibition on 7/370 kinases, while ibr, acala, and M27 had more off-target binding (17, 15 and 23 kinases, respectively) at their respective 100X IC50 (BTK) concentrations (Figure 2).
Conclusion: In pts with B-cell malignancies intolerant to ibr and/or acala, zanu treatment resulted in continued disease control or improved response. Zanu was well-tolerated, and most AEs that led to discontinuation of previous BTKi therapy did not recur or recurred at a lower grade. In support of clinical findings, differentiation between BTKi selectivity profiles favor zanu over ibr and acala.
Display omitted
Shadman: Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, and Atara Biotherapeutics, Adaptimmune: Consultancy; Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding; Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, and Atara Biotherapeutics, Adaptimmune: Membership on an entity's Board of Directors or advisory committees. Flinn: Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sa
Full text
Available for:
IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
PDF
