Sharon Wilks

Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial

BACKGROUND Disease progression in patients with HER2-positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signalling pathway. We aimed to assess whether the addition of the mTOR inhibitor everolimus to trastuzumab might restore sensitivity to trastuzumab. METHODS In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited women with HER2-positive, trastuzumab-resistant, advanced breast carcinoma who had previously received taxane therapy. Eligible patients were randomly assigned (1:1) using a central patient screening and randomisation system to daily everolimus (5 mg/day) plus weekly trastuzumab (2 mg/kg) and vinorelbine (25 mg/m(2)) or to placebo plus trastuzumab plus vinorelbine, in 3-week cycles, stratified by previous lapatinib use. The primary endpoint was progression-free survival (PFS) by local assessment in the intention-to-treat population. We report the final analysis for PFS; overall survival follow-up is still in progress. This trial is registered with ClinicalTrials.gov, number NCT01007942. FINDINGS Between Oct 26, 2009, and May 23, 2012, 569 patients were randomly assigned to everolimus (n=284) or placebo (n=285). Median follow-up at the time of analysis was 20.2 months (IQR 15.0-27.1). Median PFS was 7.00 months (95% CI 6.74-8.18) with everolimus and 5.78 months (5.49-6.90) with placebo (hazard ratio 0.78 [95% CI 0.65-0.95]; p=0.0067). The most common grade 3-4 adverse events were neutropenia (204 [73%] of 280 patients in the everolimus group vs 175 [62%] of 282 patients in the placebo group), leucopenia (106 [38%] vs 82 [29%]), anaemia (53 [19%] vs 17 [6%]), febrile neutropenia (44 [16%] vs ten [4%]), stomatitis (37 [13%] vs four [1%]), and fatigue (34 [12%] vs 11 [4%]). Serious adverse events were reported in 117 (42%) patients in the everolimus group and 55 (20%) in the placebo group; two on-treatment deaths due to adverse events occurred in each group. INTERPRETATION The addition of everolimus to trastuzumab plus vinorelbine significantly prolongs PFS in patients with trastuzumab-resistant and taxane-pretreated, HER2-positive, advanced breast cancer. The clinical benefit should be considered in the context of the adverse event profile in this population.

Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2–Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3

PURPOSE Two recent phase III trials, BOLERO-1 and BOLERO-3 (Breast Cancer Trials of Oral Everolimus), evaluated the addition of everolimus to trastuzumab and chemotherapy in human epidermal growth factor receptor 2-overexpressing advanced breast cancer. The current analysis aimed to identify biomarkers to predict the clinical efficacy of everolimus treatment. METHODS Archival tumor samples from patients in BOLERO-1 and BOLERO-3 were analyzed using next-generation sequencing, immunohistochemistry, and Sanger sequencing. RESULTS Biomarker data were available for 549 patients. PIK3CA activating mutations and PTEN loss were reported in 30% and 16% of BOLERO-1 samples and in 32% and 12% of BOLERO-3 samples, respectively. PI3K pathway was hyperactive (PIK3CA mutations and/or PTEN loss and/or AKT1 mutation) in 47% of BOLERO-1 and 41% of BOLERO-3 samples. In both studies, differential progression-free survival (PFS) benefits of everolimus were consistently observed in patient subgroups defined by their PI3K pathway status. When analyzing combined data sets of both studies, everolimus was associated with a decreased hazard of progression in patients with PIK3CA mutations (hazard ratio [HR], 0.67; 95% CI, 0.45 to 1.00), PTEN loss (HR, 0.54; 95% CI, 0.31 to 0.96), or hyperactive PI3K pathway (HR, 0.67; 95% CI, 0.48 to 0.93). Patients with wild-type PIK3CA (HR, 1.10; 95% CI, 0.83 to 1.46), normal PTEN (HR, 1.00; 95% CI, 0.80 to 1.26), or normal PI3K pathway activity (HR, 1.19; 95% CI, 0.87 to 1.62) did not derive PFS benefit from everolimus. CONCLUSION This analysis, although exploratory, suggests that patients with human epidermal growth factor receptor 2-positive advanced breast cancer having tumors with PIK3CA mutations, PTEN loss, or hyperactive PI3K pathway could derive PFS benefit from everolimus.

PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer

Introduction: Therapeutic antibodies to immune checkpoints show promising results. Programmed death‐ligand 1 (PD‐L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD‐L1 receptor (programmed death 1). We investigated PD‐L1 protein expression and messenger RNA (mRNA) levels in SCLC. Methods: PD‐L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC) with SP142 and Dako 28‐8 PD‐L1 antibodies and in situ hybridization in primary tumor tissue microarrays in both tumor cells and tumor‐infiltrating immune cells (TIICs) obtained from a limited‐disease SCLC cohort of 98 patients. An additional cohort of 96 tumor specimens from patients with extensive‐disease SCLC was assessed for PD‐L1 protein expression in tumor cells with Dako 28‐8 antibody only. Results: The overall prevalence of PD‐L1 protein expression in tumor cells was 16.5%. In the limited‐disease cohort, the prevalences of PD‐L1 protein expression in tumor cells with SP142 and Dako 28‐8 were 14.7% and 19.4% (tumor proportion score cutoff ≥1%) and PD‐L1 mRNA ISH expression was positive in 15.5% of tumor samples. Increased PD‐L1 protein/mRNA expression was associated with the presence of more TIICs (p < 0.05). The extensive‐disease cohort demonstrated a 14.9% positivity of PD‐L1 protein expression in tumor cells with Dako 28‐8 antibody. Conclusions: A subset of SCLCs is characterized by positive PD‐L1 and/or mRNA expression in tumor cells. Higher PD‐L1 and mRNA expression correlate with more infiltration of TIICs. The prevalence of PD‐L1 in SCLC is lower than that published for NSCLC. The predictive role of PD‐L1 expression in SCLC treatment remains to be established.

PD01-01: Randomized Phase II Trial of Fulvestrant with or without Dasatinib in Postmenopausal Patients with Hormone Receptor-Positive Metastatic Breast Cancer Previously Treated with an Aromatase Inhibitor.

Introduction: Fulvestrant is an effective endocrine therapy in patients with ER+ metastatic breast cancer (MBC) that has become resistant to non-steroidal aromatase inhibitors (NSAI). Dasatinib is a potent, broad spectrum ATP-competitive inhibitor of SRC tyrosine kinase activity that can lead to endocrine therapy resistance and late bone metastases. Dasatinib inhibits proliferation of cancer cell lines that express activated SRC. Inhibition of SRC signaling may overcome the endocrine resistance of HR+ MBC. We sought to determine whether addition of dasatinib to fulvestrant would increase progression-free survival (PFS) over fulvestrant alone in MBC. Methods: This is a randomized phase II study including patients with evaluable or measurable ER+ MBC whose disease had progressed while on adjuvant or metastatic NSAI. Patients were stratified to ≤ 2 yrs vs > 2 yrs from initial breast cancer diagnosis to first diagnosis of metastatic disease and randomly assigned 1:1 to Arm 1 (loading dose of fulvestrant 500 mg followed by 250 mg IM and dasatinib 100 mg PO QD) or Arm 2 (single-agent fulvestrant 250 mg IM). Following FDA approval in 2010 of the 500 mg dose, a loading dose (500 mg) of fulvestrant on Day 1 was followed by 500 mg on Day 15 of Cycle 1 and on Day 1 of each subsequent cycle (n=40 patients received the higher dose). Arm 2 patients who progressed while on fulvestrant could cross over to receive fulvestrant plus dasatinib. The primary objective was median PFS. Secondary objectives included overall survival (OS), overall response rate (ORR), and safety. Results: The study included 99 patients, 50 in Arm 1 (combination) and 49 in Arm 2 (fulvestrant alone). Results for Arm 1 and Arm 2, respectively, were: median PFS 6.0 and 5.3 months; median OS 17.0 and 21.7 months; and clinical benefit rates (CBR) (PR+SD ≥6 months) were 14 (28.0%, 95%CI=16.2%-42.5%) and 16 (32.7%, 95%CI=19.9%-47.5%) months. In Arm 1 and Arm 2, 24% and 8% developed grade 1/2 pleural effusion; 34% and 10% developed grade 1/2 diarrhea, 40% and 6% developed grade 1/2 nausea, and 30% and 18% developed grade 1/2 fatigue. Six patients on Arm 1 stopped dasatinib due to AEs, mainly pleural effusion and dyspnea. Eighteen (37%) Arm 2 patients crossed over to receive combined fulvestrant/dasatinib at disease progression on fulvestrant. Median PFS for crossover patients was 3.8 months, with the longest duration of treatment being 12 and 15 months in 2 patients. Conclusions: The addition of dasatinib to fulvestrant in ER+ postmenopausal MBC patients whose disease had progressed through an NSAI did not improve PFS, CBR, or OS. The combination of fulvestrant and dasatinib in patients with ER+ MBC was well tolerated. Formalin-fixed paraffin-embedded archival BC tissue is being analyzed for SRC-related signature to determine whether a subset of patients benefit from dasatinib. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD01-01.

APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy

AIM APF530, extended-release granisetron, provides sustained release for ≥5 days for acute- and delayed-phase chemotherapy-induced nausea and vomiting (CINV). We compared efficacy and safety of APF530 versus ondansetron for delayed CINV after highly emetogenic chemotherapy (HEC), following a guideline-recommended three-drug regimen. METHODS HEC patients received APF530 500 mg subcutaneously or ondansetron 0.15 mg/kg intravenously, with dexamethasone and fosaprepitant. Primary end point was delayed-phase complete response (no emesis or rescue medication). RESULTS A higher percentage of APF530 versus ondansetron patients had delayed-phase complete response (p = 0.014). APF530 was generally well tolerated; treatment-emergent adverse event incidence was similar across arms, mostly mild-to-moderate injection-site reactions. CONCLUSION APF530 versus the standard three-drug regimen provided superior control of delayed-phase CINV following HEC. ClinicalTrials.gov : NCT02106494.

APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide–based highly emetogenic chemotherapy regimens: a post hoc subgroup analysis of the Phase III randomized MAGIC trial

Background APF530, a novel extended-release granisetron injection, was superior to ondansetron in a guideline-recommended three-drug regimen in preventing delayed-phase chemotherapy-induced nausea and vomiting (CINV) among patients receiving highly emetogenic chemotherapy (HEC) in the double-blind Phase III Modified Absorption of Granisetron In the prevention of CINV (MAGIC) trial. Patients and methods This MAGIC post hoc analysis evaluated CINV prevention efficacy and safety of APF530 versus ondansetron, each with fosaprepitant and dexamethasone, in patient subgroup receiving an anthracycline plus cyclophosphamide (AC) regimen. Patients were randomized 1:1 to APF530 500 mg subcutaneously (granisetron 10 mg) or ondansetron 0.15 mg/kg intravenously (IV) (≤16 mg); stratification was by planned cisplatin ≥50 mg/m2 (yes/no). Patients were to receive fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1, then dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3 and 4. Patients were mostly younger females (APF530 arm, mean age 54.1 years, female, 99.3%; ondansetron arm, 53.8 years, female 98.3%). The primary end point was delayed-phase (>24–120 hours) complete response (CR). Results APF530 versus ondansetron regimens achieved numerically better CINV control in delayed and overall (0–120 hours) phases for CR, complete control, total response, rescue medication use, and proportion with no nausea. APF530 trends are consistent with the overall population, although not statistically superior given the underpowered AC subgroup analysis. The APF530 regimen in this population was generally well tolerated, with safety comparable to that of the overall population. Conclusion APF530 plus fosaprepitant and dexamethasone effectively prevented CINV among patients receiving AC-based HEC, a large subgroup in whom CINV control has traditionally been challenging.

Clinical effects of prior trastuzumab on combination eribulin mesylate plus trastuzumab as first-line treatment for HER2+ locally recurrent or metastatic breast cancer (MBC): Results from a phase 2, single-arm, multicenter study.

139 Background: Eribulin mesylate, a novel nontaxane microtubule dynamics inhibitor in the halichondrin class of antineoplastic drugs, is indicated for women with MBC who previously received ≥ 2 chemotherapy regimens in the metastatic setting. Primary data from a phase 2 trial on first-line combination eribulin + trastuzumab (TRAS) in HER2+ patients (pts) showed a 71% objective response rate (ORR) and tolerability consistent with the known profile of these agents. Here we present prespecified endpoint data for this study by prior TRAS use. METHODS Pts with HER2+ MBC who had not received prior chemotherapy for MBC received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 21-day cycle and initial TRAS (8 mg/kg IV/day 1), followed by 6 mg/kg/day 1 of each subsequent cycle. Response, progression-free survival (PFS), and tolerability were assessed in patients who had and had not received prior TRAS treatment. RESULTS The 52 pts (median age, 59.5 years) received combination eribulin + TRAS, for a median treatment duration of ~30 weeks; 40% (n=21) were previously treated with TRAS in the neo-adjuvant/adjuvant setting. There was median of 23 months since completion of adjuvant treatment prior to retreatment with eribulin + TRAS for first-line MBC.Efficacy, assessed by ORR, clinical benefit rate (CBR), PFS, and duration of response (DOR), was largely consistent in pts who received prior TRAS relative to pts who had not received prior TRAS (see table). Overall, grade (G) 3-5 adverse events (AEs), treatment-related AEs (TRAEs), and discontinuations (d/c) were similar between groups (Table). CONCLUSIONS In this phase 2 single-arm trial in pts with HER2+ MBC, eribulin + TRAS demonstrated activity and was well tolerated as first-line treatment, irrespective of prior (neo) adjuvant TRAS treatment. CLINICAL TRIAL INFORMATION NCT01269346. [Table: see text].

Abstract 4159: Characterization of the T-cell receptor (TCR) repertoire in extensive disease small cell lung cancer (ED SCLC)

Background: The current study explores T-cell (TC) clonality and molecular factors associated with this metric. Tumors employ multiple mechanisms to evade antitumor immune responses. One process involves TC inhibition via upregulation of immune checkpoint (IC) ligands in the tumor microenvironment (TME). Gradual upregulation of inhibitory receptor at their cellular surface results in a decreased capacity to proliferate and activate cytotoxic pathways against tumor cells presenting antigenic peptides.1 In melanoma, this subset of exhausted TCs has been described as highly clonal, where the majority of PD-1-expressing TC population shares the same TCR sequence specific against the same antigenic fragment.2 Previous studies have demonstrated that a clonal TCR repertoire appears to be associated in part with therapeutic responses during IC blockade.3 Methods: We performed TCR sequencing on 82 blood and 73 archival tumor tissue samples collected from ED SCLC patients (pts) in an ongoing longitudinal cohort study in US community oncology practices. Of these, 82 blood and 48 tissue samples had sufficient material available to quantify a clonality metric. To quantify TC abundance as a fraction of total nucleated cells, 82 blood and 58 tissue samples had sufficient material available. Results: Within the subset of 48 tumor samples, a more clonal (ie, less diverse) TCR repertoire was associated with less necrosis (P≤0.012) and lower levels of inflammatory cell infiltration in the local TME (P≤0.021). When pts were divided into 2 equal groups according to the median clonality level, pts with a less clonal TCR repertoire (n = 24/48) who were treated with non-immune-targeted therapy trended toward a longer overall survival (OS; 446 vs 301 days; P≤0.039). In contrast, the percentage of TCs in the TME did not correlate with improved survival (P≤0.412), necrosis (P≤0.131), and inflammation (P≤0.615). This observation differs from results in melanoma describing the impact of IC blockade where pts responding to therapy were associated with a more clonal TME TC population and increased CD8 TCs in the tumor compartment and at the invasive margin.3 In blood, while a less clonal TCR repertoire was associated with a similar but non-significant trend toward longer survival (P≤0.148), pts with increased TC abundance had longer OS (P≤0.025). No association was observed between clonality in TME and clonality (P≤0.571) or TC abundance (P≤0.965) in blood. Conclusion: We hypothesize that a diverse TCR repertoire in the TME and increased peripheral TC abundance are 2 predictors of longer OS in ED SCLC. To further explore factors that may influence TC responses in ED SCLC, the current TCR sequencing results will be integrated with transcriptome and whole genome sequencing analyses. References 1. Wherry EJ. Nat Immunol. 2011;12:492-99. 2. Gros A, et al. J Clin Invest. 2014;124:2246-59. 3. Tumeh PC, et al. Nature. 2014;515:568-71. Citation Format: Maen Hussein, Sharon Wilks, Marc Monte, Donald A. Richards, Jerome H. Goldschmidt, David Waterhouse, Lisu Wang, Saumya Pant, Erik Yusko, Ryan O. Emerson, Darin M. Taverna, Kaushal Desai, Spyro Mousses, Zhenhao Qi, Jason D. Hipp, Harlan Robins, Kimary Kulig, Cory Batenchuk. Characterization of the T-cell receptor (TCR) repertoire in extensive disease small cell lung cancer (ED SCLC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4159.

Abstract P1-10-07: Phase 3 comparison of APF530 versus ondansetron, each in a guideline-recommended 3-drug regimen for prevention of chemotherapy-induced nausea and vomiting due to anthracycline + cyclophosphamide (AC)–based highly emetogenic chemotherapy (HEC) regimens: A post hoc subgroup analysis of the MAGIC trial

Background: Managing delayed chemotherapy-induced nausea and vomiting (CINV) associated with HEC is an unmet need. AC-based HEC is often administered to breast cancer patients (pts), a mostly female, high-CINV-risk population. APF530, an extended-release formulation of granisetron, demonstrated superior complete response (CR; no emesis [vomiting, retching] + no rescue medication use) in delayed-phase (>24-120 h) CINV with HEC (ASCO criteria) vs ondansetron (Ond) (65% vs 57%, P =0.014), each combined with a neurokinin-1 antagonist and dexamethasone (Dex) (NCT02106494). This post hoc analysis evaluated efficacy and safety of APF530 in pts receiving AC-based therapy. Methods: In this randomized, double-blind, multicenter trial, pts scheduled to receive single-day HEC were stratified by cisplatin ≥50 mg/m 2 yes/no and randomized 1:1 to APF530 500 mg SC (granisetron 10 mg) or Ond 0.15 mg/kg IV. Pts received concomitant Dex 12 mg IV and fosaprepitant 150 mg IV on day 1 and oral Dex on days 2-4. The primary end point was CR in the delayed phase. Secondary and other end points included CR in acute (0-24 h) and overall (0-120 h) phases, and complete control (CC; CR and no more than mild nausea) and total response (TR; CR and no nausea) in acute, delayed, and overall phases. Rates were compared using 95% confidence intervals (CIs) for treatment differences; post hoc analysis was not powered to detect treatment differences in the AC subgroup. Safety assessments included adverse events (AEs), injection-site reactions (ISRs), laboratory parameters, and vital signs. Results: A total of 589/902 pts (65%) in the modified intent-to-treat population received AC-based HEC (APF530 291, Ond 298). Baseline demographics were balanced between treatment arms. The majority of pts in the AC subgroup were female (APF530 99%, Ond 98%). Delayed-phase CR was higher with APF530 vs Ond, approaching statistical significance (APF530 64%, Ond 56%; P =0.062) in the AC subgroup, similar to the benefit seen in the larger study. No appreciable benefit of APF530 vs Ond was observed in the acute phase, and trends favorable to APF530 were observed in the overall phase (Table). APF530 was well tolerated. Most AEs were ISRs, generally mild or moderate, and resolved by end of study. Conclusions: APF530 demonstrated an apparent clinical benefit in delayed-phase CR in pts receiving AC-based HEC, concordant with the statistically significant benefit seen in the overall study population. Prevention of CINV in this patient population continues to be a treatment challenge and further investigation is needed. Citation Format: Schnadig I, Agajanian R, Dakhil S, Taylor C, Wilks S, Cooper W, Mosier M, Payne Y, Klepper M, Vacirca J. Phase 3 comparison of APF530 versus ondansetron, each in a guideline-recommended 3-drug regimen for prevention of chemotherapy-induced nausea and vomiting due to anthracycline + cyclophosphamide (AC)–based highly emetogenic chemotherapy (HEC) regimens: A post hoc subgroup analysis of the MAGIC trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-07.

Abstract P6-13-21: Phase 1 study of GR antagonist mifepristone (M) in combination with eribulin (E) in advanced solid tumors, with dose expansion in patients (pts) with GR-positive triple-negative breast cancer (TNBC)

Background: High tumor GR expression is associated with poor prognosis in estrogen receptor (ER) negative early-stage breast cancer. Co-treatment with M, a GR antagonist, potentiates effects of chemotherapy in ER- breast cancer xenograft studies. Herein we describe results of a phase 1 dose-escalation study of M plus E, with an ongoing dose expansion cohort in pts with GR+ TNBC. Objectives: Determine 1) safety and tolerability, 2) recommended phase 2 dose (RP2D) of M + E, and 3) characterize pharmacokinetics (PK) and clinical activity of M in pts with GR+ TNBC. Methods: Eligibility: 1) relapsed/refractory breast, ovarian, prostate, urothelial, sarcoma, or non-small cell lung cancer; 2) 2-5 prior chemotherapy regimens for advanced disease; 3) ECOG PS 0-1; and 4) adequate end-organ function. Study used a 3 + 3 dose escalation scheme. After a 7 day lead-in of M alone, M was administered by mouth daily in combination with E given IV on days 1 and 8 of a 21 day cycle. Results: 13 pts in Part 1 Dose escalation with metastatic breast cancer (MBC) were treated with M+E: 5 TNBC, 8 GR+ tumors, 2 GR- tumors, and 3 of unknown GR status. Pts were treated at 3 dose levels (DL)[M mg/d, E mg/m2]: 3 at DL1 [600, 1.1] 4 at DL-1a [300, 1.4], and 6 at DL-1 [300, 1.1]. Median duration of treatment was 90+ days. Neutropenia leading to delay of E was dose limiting in 4 pts. CTAE Grade 3/4 neutropenia was observed in 10 pts over all DL, but easily managed (9 pts with growth factor support). Other grade 3+ toxicities were neuropathy (2 pts) and onycholysis (1 pt). No other significant toxicity was noted. RP2D was determined as 300mg/d M and 1.1mg/m2 E. At this DL there were no DLTs. PK of M and E were as predicted from published literature with no evidence of drug-drug interaction (DDI). A total of 6 pts received this dose (3 TNBC; 3 MBC). All 3 TNBC were GR+. 1 had partial response, 1 had stable disease, and 1 had progressive disease. A phase I/II study of M+E is now in progress. To date, 3 GR+ TNBC pts have been treated for a median of 28+ days. Conclusion: M + E is a novel combination designed to improve antitumor activity. It is well tolerated with evidence of clinical activity and no evidence of DDI. RP2D is 300mg M + E 1.1mg/m2. Study is ongoing in expansion phase where recruitment is limited to pts with GR+ TNBC. Additional PK and clinical data will be presented. Citation Format: Wilks S, Modiano M, Spira A, Becerra C, Walling J, Nguyen D, Baker G, Conzen SD, Nanda R. Phase 1 study of GR antagonist mifepristone (M) in combination with eribulin (E) in advanced solid tumors, with dose expansion in patients (pts) with GR-positive triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-13-21.