scholarly journals Checkpoint inhibition in combination with an immunoboost of external beam radiotherapy in solid tumors (CHEERS): study protocol for a phase 2, open-label, randomized controlled trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mathieu Spaas ◽  
Nora Sundahl ◽  
Eva Hulstaert ◽  
Vibeke Kruse ◽  
Sylvie Rottey ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Treatment Schedule ◽  
Advanced Solid Tumors ◽  
Cell Lung Carcinoma ◽  
Free Survival ◽  
Link Type ◽  
Study Results

Abstract Background While the introduction of checkpoint inhibitors (CPIs) as standard of care treatment for various tumor types has led to considerable improvements in clinical outcome, the majority of patients still fail to respond. Preclinical data suggest that stereotactic body radiotherapy (SBRT) could work synergistically with CPIs by acting as an in situ cancer vaccine, thus potentially increasing response rates and prolonging disease control. Though SBRT administered concurrently with CPIs has been shown to be safe, evidence of its efficacy from large randomized trials is still lacking. The aim of this multicenter randomized phase II trial is to assess whether SBRT administered concurrently with CPIs could prolong progression-free survival as compared to standard of care in patients with advanced solid tumors. Methods/design Ninety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (≤ or > 3 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study’s primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples. Discussion: The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials. Trial registration Clinicaltrials.gov identifier: NCT03511391. Registered 17 April 2018.

scholarly journals Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

Phase 1/2 study of eprenetapopt (APR-246) in combination with pembrolizumab in patients with solid tumor malignancies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS3161-TPS3161
Author(s):  
Ecaterina Elena Dumbrava ◽  
Amit Mahipal ◽  
Xin Gao ◽  
Geoffrey Shapiro ◽  
Jason S. Starr ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Mononuclear Cells ◽  
Phase 1 ◽  
Objective Response ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Tumor Growth Inhibition ◽  
Advanced Solid Tumors ◽  
Peripheral Blood Mononuclear

TPS3161 Background: The p53 pathway has been implicated in antitumor immunity, including antigen presentation and T-cell proliferation. Loss of p53 function can increase resistance to immunotherapy across many tumor types. Eprenetapopt (eprenet) is a small molecule that stabilizes the folded structure of p53, resulting in activation of mutant p53 and stabilization of wild-type (WT) p53. It also targets the cellular redox homeostasis, resulting in induction of apoptosis in tumor cells. In vivo, mice carrying supernumerary copies of the TP53 gene harbor a pro-inflammatory tumor microenvironment, an effect recapitulated in TP53 normal-copy mice treated with eprenetapopt. Combining eprenetapopt and anti-PD1 or anti-CTLA4 therapy resulted in enhanced tumor growth inhibition and improved survival in TP53 WT mice inoculated with B16 melanoma and MC38 colon adenocarcinoma cells . Based on these results, we hypothesized that eprenet-induced p53 stabilization may augment response to immunotherapy. To test this hypothesis, we are conducting a phase 1b/2 study of eprenet in combination with pembrolizumab (eprenet+pembro) in pts with solid tumors. Methods: The primary objectives are to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) and to assess the safety and tolerability of eprenet+pembro in pts with advanced solid tumors. The secondary objectives are to estimate the anti-tumor activity and to describe the pharmacokinetics of the combination. Exploratory objectives include assessing predictive and pharmacodynamic markers of response. The study includes a safety lead-in with a 3+3 dose de-escalation design for pts with advanced solid tumors with known tumor TP53 mutation status ( TP53 WT is acceptable) (max 18 pts), followed by expansion cohorts in pts with NSCLC, gastric/GEJ and urothelial cancer (max 100 pts). In expansion, pts with urothelial and gastric cancers must be naïve to anti-PD-1/ L1 therapy. Eprenet is given IV once daily on Days 1–4 while pembro is administered on Day 3 of each 21-day cycle. The RP2D of eprenet+pembro is considered the dose at which ≤ 1 of 6 pts in a cohort has a dose-limiting toxicity (DLT). Primary endpoints are occurrence of DLTs, adverse events (AEs) and serious AEs with eprenet+pembro. Key secondary endpoints are best objective response, progression free survival and overall survival. Exploratory endpoints include gene mutations by next generation sequencing (including TP53), mRNA expression, multiplex immunohistochemistry and transcriptomics, multiplex flow cytometry on peripheral blood mononuclear cells and cytokines in serum. Continuous monitoring of toxicity will be conducted. The trial opened in May 2020 and is actively enrolling patients. Clinical trial information: NCT04383938.

scholarly journals P14.15 Benefit of Bevacizumab for recurrent glioblastoma. Results of 81 patients from a single institution

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii69-iii69
Author(s):  
O Absalyamova ◽  
G Kobiakov ◽  
G Agabekyan ◽  
A Poddubsky ◽  
A Belyashova ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Rapid Progression ◽  
Concomitant Disease ◽  
Free Survival ◽  
Phase Iii Trials ◽  
Continuous Application

Abstract BACKGROUND No standard of care has been established for patients with progressive glioblastoma (rGBM). Previous studies suggested that bevacizumab (BEV) is safe and produces responses that result in a decreased use of glucocorticoids and increased progression-free survival (PFS) with an unclear effect on overall survival (OS). Crossover to BEV in the control arm is the possible reason why the advantage of BEV has not been proven in Phase III trials. We retrospectively analyzed own results of BEV treatment in rGBM. MATERIAL AND METHODS 81 patients progressed after radiotherapy plus concomitant and maintenance temozolomide (TMZ) and undergo BEV as monotherapy (BevMo, 11 patients) or in combinations (Irinotecan (BevI) - 53, lomustine (BevL)- 11, TMZ (BevT) - 6. Median age 54 years. Among them 33 patients were re-irradiated: 11 - radiosurgery (RS), 20 fractionated irradiation (RT), 2 - RS+RT. 33 patients continued BEV after progression with changing or adding cytostatic. PFS was calculated from the date of verification, PFS1 - from the date of 1-st progression, PFS2 - from the date of 2-nd progression. RESULTS Median PFS was 9.0 ([CI] 7.0–10.9) months. Median PFS1 was 10.5 ([CI] 8.1–12.9) months. In the BevMo, BevI, BevL, BevT group PFS1 was 15.7, 10.1, 10.5, 13.2 months, respectively, p=0.7. Objective response (OR) was reached in 34%, stable disease (SD) in 28%, progression (PD) in 37% patients. 16 patients stopped BEV without progression (4-patient`s decision, 7- doctor`s decision, 2 - adverse event, 3 - concomitant disease). Median time of BEV treatment was 11.6 months. Median BEV-free interval till progression was 3.7 months. 33 patients continued or restarted BEV after progression. Median PFS2 was 8.0 ([CI] 4.9–11.1) months. The median OS from the date of 1-st progression was 23.5 months ([CI] 18.7–27.4). In groups with RT, RS, RS+RT and no re-irradiarion OS was 24.6 ([CI] 17.6–31.5), 35.4 ([CI] 35.0–35.8), 17.8, 20.6 ([CI] 15.2–26.0), respectively, p=0.2. CONCLUSION OS in our group is outrageously high. Maintaining BEV after progression was effective. In our group BEV discontinuation led to rapid progression. The resumption of Bev with progression was effective, which indicates the advisability of its continuous application.

scholarly journals More than a Decade of Tyrosine Kinase Inhibitors in the Treatment of Solid Tumors: What We Have Learned and What the Future Holds

2015 ◽  
Vol 10s3 ◽  
pp. BMI.S22436 ◽  
Author(s):  
Maria Vergoulidou
Keyword(s):  
Tyrosine Kinase ◽  
Small Molecules ◽  
Solid Tumors ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Free Treatment

The use of tyrosine kinase inhibitors (TKIs) in the treatment of solid tumors is the expected standard of care for many types of tumors. Since the description of signal transduction pathways, followed by the development of small molecules designed to inhibit those pathways, there has been significant improvement not only in progression-free survival and overall survival but also in aiming toward chemotherapy-free treatment of solid tumors to maximize quality of life. This article reviews available TKIs and discusses toxicity, dosing, and resistance.

A dose attenuated schedule of irinotecan and capecitabine in combination with celecoxib in advanced colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3584-3584
Author(s):  
B. F. El-Rayes ◽  
A. F. Shields ◽  
U. Vaishampayan ◽  
L. K. Heilbrun ◽  
M. M. Zalupski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Free Survival ◽  
Study Results ◽  
Cox 2

3584 Background: The cyclooxygenase-2 (COX-2) enzyme is overexpressed in the majority of colorectal cancers. Inhibition of the COX-2 enzyme can sensitize colorectal cancer cells to the apoptotic effects of chemotherapeutic agents and block angiogenesis. This phase II study was undertaken to determine the effects of adding celecoxib to a dose attenuated irinotecan and capecitabine regimen. Methods: The primary objective was to estimate the objective response rate of patients with metastatic colorectal cancer treated with irinotecan, capecitabine, and celecoxib. Previously untreated patients, except for adjuvant therapy, with metastatic colorectal adenocarcinoma were eligible for this study. Patients received irinotecan 70 mg/m2 (over 30 minutes) on days 1 and 8, and capecitabine 2,000 mg/m2/day from day 1 to 14 of a 21-day cycle. Celecoxib was administered at a dose of 400 mg twice-daily starting on day -7 until termination from study. Results: A total of 51 patients (median age 58 years) have been enrolled on the study. The results presented are for the first 48 patients registered to the study. Median performance status was 1. A median number of 5.5 cycles (range 0- 18) were administered. In an intention to treat analysis, objective response rate was 50%. The median progression free survival was 6.9 months (90%CI; 4.7–8.2). Median survival is ≥19.4 months. No treatment related deaths were observed. The only grade 4 toxicity was diarrhea in 2 (4%) patients. Grade 3 toxicities were diarrhea (33%), hand-foot syndrome (8%), nausea (13%), vomiting (8%) and neutropenia (12%). Conclusion: Lowering the dose intensity of irinotecan in this study did not appear to compromise the treatment outcome and markedly improved the therapeutic index of this combination. Celecoxib can be safely administered in combination with irinotecan and capecitabine. Based on the observed progression free survival and response rate, the regimen has promising activity. No significant financial relationships to disclose.

scholarly journals Impact of ALK Inhibitors in Patients With ALK-Rearranged Nonlung Solid Tumors

2021 ◽  
pp. 756-766
Author(s):  
Yuki Takeyasu ◽  
Hitomi S. Okuma ◽  
Yuki Kojima ◽  
Tadaaki Nishikawa ◽  
Maki Tanioka ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Alk Rearrangement ◽  
Free Survival ◽  
Anaplastic Lymphoma ◽  
Treatment Interruptions ◽  
Alk Positive

PURPOSE Anaplastic lymphoma kinase ( ALK) rearrangement is a well-known driver oncogene in non–small-cell lung cancer and has also been identified in other types of tumors. However, there is limited evidence on the clinical response to ALK tyrosine kinase inhibitors (TKIs), such as alectinib and crizotinib, in rare tumors with ALK fusion. We evaluated the therapeutic effect of ALK-TKIs in rare ALK-rearranged tumors. PATIENTS AND METHODS Between April 2012 and April 2019, clinical outcomes and characteristics of patients with ALK-rearranged nonlung solid tumors who received ALK-TKIs (alectinib and/or crizotinib) outside of clinical trials were reviewed. Expression and/or rearrangement of ALK was evaluated by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing. The tumor response was assessed according to RECIST (version 1.1). Progression-free survival was estimated from initial ALK-TKI initiation until progression. RESULTS We identified seven patients (inflammatory myofibroblastic tumors, n = 3; ALK-positive histiocytosis, n = 1; histiocytic sarcoma, n = 1; osteosarcoma, n = 1; and parotid adenocarcinoma, n = 1), with a median age of 17 years. Two rare ALK fusions, namely, CTNNA1-ALK and ITSN2-ALK, were identified. As initial ALK-TKI therapy, five patients received alectinib and two received crizotinib. The objective response rate for the initial ALK-TKI therapy was 85.7% (95% CI, 44 to 97), including two patients who received alectinib and achieved complete response. The median progression-free survival was 8.1 months (range, 1.7 to not estimable). There were no treatment interruptions or dose reductions because of adverse events caused by alectinib. CONCLUSION This study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with ALK-rearranged nonlung solid tumors.

Safety and Activity of Varlilumab, a Novel and First-in-Class Agonist Anti-CD27 Antibody, in Patients With Advanced Solid Tumors

2017 ◽  
Vol 35 (18) ◽  
pp. 2028-2036 ◽  
Author(s):  
Howard A. Burris ◽  
Jeffrey R. Infante ◽  
Stephen M. Ansell ◽  
John J. Nemunaitis ◽  
Geoffrey R. Weiss ◽  
...  
Keyword(s):  
T Cell ◽  
Antitumor Activity ◽  
Solid Tumors ◽  
T Cell Activation ◽  
Dose Escalation ◽  
Costimulatory Molecule ◽  
Progression Free Survival ◽  
Advanced Solid Tumors ◽  
Free Survival ◽  
Metastatic Rcc

Purpose CD27, a costimulatory molecule on T cells, induces intracellular signals that mediate cellular activation, proliferation, effector function, and cell survival upon binding to its ligand, CD70. Varlilumab is a novel, first-in-class, agonist CD27 antibody that stimulates the CD27 pathway, which results in T-cell activation and antitumor activity in tumor models. This first-in-human, dose-escalation and expansion study evaluated the safety, pharmacology, and activity of varlilumab in patients with advanced solid tumors. Methods In a 3 + 3 dose-escalation design (n = 25), patients received a single dose of varlilumab (0.1, 0.3, 1.0, 3.0, or 10 mg/kg intravenously) with a 28-day observation, followed by up to five multidose cycles (one dose per week for 4 weeks), depending on tumor response. Expansion cohorts were initiated at 3.0 mg/kg in patients with melanoma (n = 16) and renal cell carcinoma (RCC; n = 15). Primary objectives were to assess the safety and the maximum tolerated and optimal biologic doses of varlilumab. Secondary objectives were to evaluate the pharmacokinetics, pharmacodynamics, and clinical antitumor activity of varlilumab. Results Exposure to varlilumab was linear and dose proportional across dose groups. Only one patient experienced a dose-limiting toxicity—grade 3 transient asymptomatic hyponatremia at the 1.0-mg/kg dose level. Treatment-related adverse events were generally grade 1 or 2 in severity. Evidence of biologic activity consistent with CD27 stimulation—chemokine induction, T-cell stimulation, regulatory T cell depletion—was observed at all dose levels. A patient with metastatic RCC experienced a partial response (78% shrinkage, progression-free survival > 2.3 years). Eight patients experienced stable disease > 3 months, including a patient with metastatic RCC with progression-free survival of > 3.9 years. Conclusion Dose escalation of varlilumab to 10 mg/kg was well tolerated without identification of a maximum tolerated dose. Varlilumab was biologically and clinically active.

Correlation of Src activation with response to dasatinib, capecitabine, oxaliplatin, and bevacizumab in advanced solid tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11036-11036
Author(s):  
John H. Strickler ◽  
Shannon McCall ◽  
Andrew B. Nixon ◽  
Herbert Pang ◽  
Christel Rushing ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Phase I Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Advanced Solid Tumors ◽  
Exact Test ◽  
Src Activation ◽  
Expansion Cohort

11036 Background: Src inhibition may augment sensitivity to chemotherapy, but in unselected patients (pts) with advanced solid tumors, src inhibitors have shown limited clinical activity. Biomarkers to predict benefit from src inhibitors in advanced solid tumors are not yet known. Methods: 22 pts (dose escalation cohort= 12 pts; colorectal cancer [CRC] expansion cohort= 10 pts) were enrolled in a phase I study to determine the safety and tolerability of the src inhibitor dasatinib with capecitabine, oxaliplatin, and bevacizumab (J Clin Oncol 29: 2011 [suppl; abstr 3586]). Src activation (src-a) was assessed in tumors from 16 evaluable pts. Src-a was measured by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded tumor samples using an antibody that selectively recognizes the active conformation of src (clone 28). A GI pathologist who was blinded to pt outcomes graded membranous src-a using a standard semi-quantitative method. The endpoint of this exploratory analysis was objective response rate ([ORR]= PR+CR). 2-sided Fisher’s Exact test was used to evaluate the association between ORR and src-a. Results: Across all tumor types, 8 tumors had no/faint src-a (IHC=0/1); 8 tumors had moderate/strong src-a (IHC≥2). Benign colonic epithelium had no src-a (IHC=0). The ORR was 75% (6/8) for pts with moderate/strong src-a versus (vs) 0% (0/8) for pts with no/faint src-a (p =0.007). In the CRC expansion cohort, the ORR was 83% (5/6) for patients with moderate/strong src-a vs 0% (0/2) for pts with no/faint src-a (p=0.107); progression free survival range was 7.9-24.4 months for pts with moderate/strong src-a. Conclusions: In this small phase I study, src-a is associated with benefit from the combination of dasatinib and oxaliplatin-based chemotherapy. Further evaluation of dasatinib in patients whose tumors demonstrate high levels of src-a may be warranted. Clinical trial information: NCT00920868.

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