CHICAGO ( TheStreet) -- Ready, set ... ASCO download! That's what a lot of healthcare investors are doing right now on the web site of the American Society of Clinical Oncology. It's ASCO abstract release day, which means summaries of thousands of cancer drug clinical trials were just made available in advance of the ASCO annual meeting at the end of the month. I'm here to help save you some time with the searching and downloading. Below are 10 ASCO research abstracts of high interest to healthcare investors, covering drugs from Abbvie ( ABBV), Ariad Pharmaceuticals ( ARIA), Arqule ( ARQL), Array Biopharma ( ARRY), BioMarin Pharma ( BMRN), Clovis ( CLVS), Curis ( CRIS), Halozyme ( HALO), Infinity Pharma ( INFI), and Pharmacylics ( PCYC). I've also written separate ASCO annual meeting stories covering new clinical data on the so-called "anti-PD-1" drugs from Bristol-Myers Squibb ( BMY), Roche ( RHHBY) and Merck ( MRK); as well as updated results from a study of Gilead Sciences' ( GILD) PI3K-delta inhibitor idelalisab. Happy abstract hunting! Abbvie and Roche Abstract No. 8520 Title: Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL). Background: BCL-2 is highly expressed in NHL, including mantle cell lymphoma (MCL), and is a promising therapeutic target as it is involved in NHL pathogenesis and mediates resistance to many cytotoxics. ABT-199 is a second generation inhibitor with 500-fold higher affinity for BCL-2. Methods: Objectives of this Ph 1 dose-escalation study include evaluations of safety, pharmacokinetics and preliminary efficacy in patients (pts) with relapsed or refractory (R/R) NHL. A single oral dose (50-400 mg) was administered followed by 6 days off drug prior to the initiation of continuous once daily dosing. Due to concerns of potential tumor lysis syndrome (TLS), a 2 to 3 wk lead-in period with step-wise escalation to the target cohort dose was implemented. Dose cohorts up to 900 mg have been evaluated to date. Results: As of January 2013, 31 pts have been enrolled (median age 68 y (range 35-85); 20 males; median prior therapies 3 (range 1-7). 13 (42%) and 4 (13%) had bulky adenopathy (greater than 5 and greater than 10 cm, respectively). The most common AEs (greater than or equal to 15% of patients) were nausea (36%), diarrhea (26%), dyspepsia, vomiting, fatigue, pyrexia and cough (16% each). Gr 3/4 AEs occurring in greater than 1 patient were anemia, neutropenia (4 pts each), and febrile neutropenia (2 pts). Two of 14 pts in cohort 5 experienced DLTs at the target dose of 600 mg: Gr 3 febrile neutropenia and Gr 4 neutropenia. Although Gr 3/4 thrombocytopenia was observed in 3 pts, it was not dose dependent. Gr 3 TLS was seen after the initial dose in 1 pt with very bulky MCL (greater than 10 cm). With a median follow-up of 5 months (range 0.5-15), 17 have discontinued: 13 due to PD, 2 due to AEs and 2 who received a BMT. Of the 29 pts evaluable for efficacy, the overall best response rate was 55% with 1 DLBCL pt achieving a CR and 15 (52%) a PR (8/8 MCL, 3/3 Waldenstrom macroglobulinemia, 2/7 follicular lymphoma and 2/7 DLBCL pts). Conclusions: ABT-199 is highly active in R/R NHL, particularly in MCL. Additional dosing and scheduling modifications are currently being explored to optimize the efficacy/safety profile of this active new agent. ABT-199 warrants further single-agent and combination trials in NHL. Ariad Pharmaceuticals Abstract No. 8031 Title: First-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies: Updated results. Background: AP26113 is a novel tyrosine kinase inhibitor (TKI) that potently inhibits mutant activated forms of anaplastic lymphoma kinase (ALK+) and epidermal growth factor receptor (EGFRm), and TKI-resistant forms including L1196M (ALK) and T790M (EGFR). AP26113 does not inhibit native EGFR. Methods: The dose finding phase (3+3 design) of this phase I/II open-label, multicenter study is ongoing in pts with advanced malignancies (except leukemia) refractory to available therapies or for whom no standard treatment exists. Initial dosing is orally once daily. Results: As of 14 Jan 2013, 44 pts were enrolled: 30 mg n=3, 60 mg n=3, 90 mg n=8, 120 mg n=8, 180 mg n=11, 240 mg n=9, 300 mg n=2; 64% female, median age 60 yrs; diagnoses: non-small cell lung cancer (NSCLC, n=37), other (n=7). 26 pts discontinued: 18 disease progression, 6 adverse event (AE), 2 deaths (sudden death, hypoxia; both possibly related). Most common AEs: nausea (45%), fatigue (39%), diarrhea (27%); most common grade 3/4 treatment-related AE: diarrhea (5%). 2 dose limiting toxicities observed: grade 3 ALT increase, 240 mg; grade 4 dyspnea, 300 mg. Doses less than 300 mg are being explored further. 21 pts had ALK+ history (18 NSCLC, 3 other). Among 18 evaluable ALK+ pts, 10 responded. 15 ALK+ pts had 0 (n=3) or 1 (n=12) prior ALK TKI (crizotinib); of these, 2/3 and 8/12 pts (67%) responded, including 2 complete responses. The longest response is 40 wks (ongoing). 4 of 5 ALK+ pts with untreated or progressing CNS lesions at baseline and with follow-up scans had evidence of radiographic improvement in CNS, including 1 pt resistant to crizotinib and LDK378 (overall response = stable disease). 16 pts had EGFRm history (15 NSCLC, 1 SCLC); 14 pts had greater than or equal to 1 prior EGFR TKI. Of 12 EGFRm pts with a follow-up scan, 1 pt (prior erlotinib) responded at 120 mg (duration 21 wks, ongoing), 6 pts had stable disease (2 ongoing, duration 7-31 wks). Conclusions: AP26113 has promising anti-tumor activity in ALK+ pts, with initial evidence of activity in EGFRm pts, and is generally well tolerated. Phase II will begin after the recommended phase II dose is determined, with 4 cohorts: crizotinib-naive NSCLC; crizotinib-resistant NSCLC; EGFR TKI-resistant NSCLC; other tumors. NCT01449461. Arqule Abstract No. 3508 Title: A randomized, placebo-controlled, phase I/II study of tivantinib (ARQ-197) in combination with cetuximab and irinotecan in patients (pts) with KRAS wild type (WT) metastatic colorectal cancer (CRC) who had received previous front-line systemic therapy. Background: Tivantinib (ARQ 197) selectively inhibits the MET receptor tyrosine kinase, which is implicated in tumor cell migration, invasion, and metastasis. Resistance to EGFR inhibitors has been associated with activation of alternative pathways including MET. Methods: Pts with advanced KRAS WT CRC that progressed on or after 1 prior line of chemotherapy and no previous treatment with an EGFR inhibitor were eligible. Pts were randomized 1:1 to receive cetuximab (500 mg/m2) and irinotecan (180 mg/m2) on days 1 and 15 every 28 days, plus oral tivantinib (360 mg twice daily BID or placebo. The primary endpoint was progression-free survival (PFS); additional endpoints include safety, objective response rate, overall survival (OS) and exploratory biomarker analyses. Results: Between Jul 2010 and Feb 2012, 122 pts were randomized; 117 pts were eligible for analysis (60 tivantinib, 57 placebo). Mean age was 57 years (range, 27-79 years); ECOG PS 0/1 55%/45%; and 81% received prior oxaliplatin. Median PFS was 8.3 months in the tivantinib arm vs 7.3 months in the placebo arm (hazard ratio
HR=0.85; 95% CI, 0.55-1.33; P = 0.38). Objective response rate (95% CI) was 45% (33%-58%) in the tivantinib arm and 33% (23%-46%) in the placebo arm. Median OS has not yet been reached but is trending in favor of tivantinib vs placebo (HR = 0.67). Among pts with prior oxaliplatin therapy, median PFS was 8.4 months for tivantinib and 7.2 months for placebo (HR = 0.67; 95% CI, 0.44-1.00; P= 0.1). The most common grade 3/4 adverse events (greater than or equal to 10%) were neutropenia, diarrhea, and nausea. Correlation of clinical outcomes with additional factors including mutation status and immunohistochemical analysis of tumor MET expression will be presented. Conclusions: Outcomes in this trial trended towards improvement with tivantinib (360mg BID) plus cetuximab and irinotecan, particularly in the subgroup who had previous oxaliplatin. Further studies are needed to identify the CRC population most likely to benefit from addition of tivantinib to standard therapy.
Array BioPharma & AstraZeneca Abstract No. 9004 Title: Phase II double-blind, randomized study of selumetinib (SEL) plus dacarbazine (DTIC) versus placebo (PBO) plus DTIC as first-line treatment for advanced BRAF-mutant cutaneous or unknown primary melanoma. Background: BRAF mutations play an oncogenic role in melanomas. Selumetinib (AZD6244, ARRY-142886) inhibits MEK1/2 downstream of B-Raf and may have an additive effect to chemotherapy. We prospectively evaluated SEL + DTIC vs PBO + DTIC in patients with stage III-IV BRAF mutation-positive advanced cutaneous or unknown primary melanoma (NCT00936221). Methods: Eligible patients (pts) received iv DTIC 1000 mg/m2, and po SEL 75 mg or matched PBO bd as first-line treatment. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety and tolerability. Results: A total of 385 pts were screened across 44 centers; 91 patients were randomized (SEL + DTIC, 45; PBO + DTIC, 46). One pt from each group did not receive the randomized treatment. Baseline characteristics were balanced between the two groups, with the exception of histology, gender and previous medications. At data cut-off, 66 deaths had occurred (73% maturity) and median follow-up was 12.3 mo. OS was longer for SEL + DTIC vs PBO + DTIC (median 13.9 vs 10.5 mo), but this did not meet statistical significance (HR 0.93; 80% CI 0.67, 1.28; 1-sided p=0.3873). PFS was significantly improved for SEL + DTIC vs PBO + DTIC, median 5.6 vs 3.0 mo (HR 0.63; 80% CI 0.47, 0.84; 1-sided p=0.021). ORR was 40% with SEL + DTIC vs 26% with PBO + DTIC. Most frequent adverse events (AEs) observed with SEL + DTIC were: nausea (64%), dermatitis acneiform (52%), diarrhea (48%), vomiting (48%), and peripheral edema (43%). AEs that led to hospitalization were higher for SEL + DTIC vs PBO + DTIC (36 vs 13%), and were mostly infections and gastrointestinal disorders. The incidence of grade greater than equal to 3 AEs (68 vs 42%), serious AEs (50 vs 18%) and discontinuation of the randomized treatment due to AEs were higher for SEL + DTIC vs PBO + DTIC (16 vs 4%). Conclusions: Clinical activity was observed in patients with BRAF mutation-positive melanoma treated with SEL + DTIC, reflected by a nonsignificant improvement in OS and a significant benefit in PFS. Tolerability of this combination was generally consistent with the monotherapy safety profiles. BioMarin Pharmaceuticals Abstract No. 2580 Title: First-in-human trial of novel oral PARP inhibitor BMN 673 in patients with solid tumors. Background: BMN 673 is the most potent and specific inhibitor of PARP1/2 in clinical development (IC50less than1nM). In tumors genetically dependent on DNA repair by homologous recombination PARP inhibition induces synthetic lethality. Methods: Pharmacokinetics (PK), pharmacodynamics (PD), safety and anti-tumor activity of BMN 673 were evaluated in a 2-stage dose-escalation study with 3-6 patients (pts)/dose level. In dose escalation (Stage 1) cycle 1 was 6 wks, with drug taken on days 1 and 8-35, for PK and PD assays, followed by daily continuous dosing in 4-wk cycles. Stage 2 (expansion at MTD) recruits pts with tumors defective in DNA repair: Ewing sarcoma, small cell lung cancer or tumors associated with BRCA mutation (mut). Results: 39 pts (33F/6M) were enrolled in 9 cohorts from 25 to 1100 ug/d that defined a MTD of 1000 ug/d. Median (range) age was 58 (19-81), PS 0 (0-1) and # of prior therapies 4 (1-13). Tumors (# with deleterious BRCA 1/2 mut) included 23 ovarian/primary peritoneal (17); 8 breast (6); 3 pancreas; 2 colon; 1 prostate (1), and 1 mullerian carcinosarcoma. 17 and 8 pts had BRCA 1 and 2 mut, respectively. Dose-limiting thrombocytopenia occurred in 1/6 and 2/5 pts at 900 and 1100 ug/d, respectively. Potentially-related adverse events in greater than 10% of pts (# grade 1 and 2/grade 3 and 4) included fatigue (10/0); nausea (10/0); flatulence (4/0); anemia (5/2); neutropenia (4/3); thrombocytopenia (1/3); and grade 1 alopecia (10). Inhibition of PARP activity in PBMCs was observed at doses greater than or equal to 100 µg/d. BMN 673 plasma concentrations peaked 1-2 hrs post-dose; exposure increased dose proportionally. Steady state plasma concentrations were reached by the end of the 2nd week of daily dosing; mean Cmax: 0.30 - 25.4 ng/mL and AUC0-24: 3.96 - 203 ng-hr/mL across the 25 to 1100 ug/d dose range after 28d of daily dosing. RECIST and/or CA-125 responses occurred at doses greater than or equal to 100 ug/d in 11/17 BRCA carrier ovarian/peritoneal cancer pts. Objective responses occurred in 2/6 BRCA-carrier breast cancer pts. Conclusions: BMN 673 is well tolerated with impressive anti-tumor activity in pts with BRCA mut with a single agent recommended Phase II trial dose of 1000 ug/d due to dose-limiting thrombocytopenia.
Clovis Oncology Abstract No. 2524 Title: First-in-human evaluation of CO-1686, an irreversible, selective, and potent tyrosine kinase inhibitor of EGFR T790M. Background: Efficacy of existing EGFR tyrosine kinase inhibitors (TKIs) in NSCLC is limited by emergence of the T790M mutation in approximately 50% of patients, and significant skin rash and diarrhea, caused by wild-type (WT)-EGFR inhibition, compromises tolerability. CO-1686 is an orally active TKI that targets common activating EGFR mutations and T790M, while sparing WT-EGFR. Animal models suggest maximal efficacy when trough plasma concentrations exceed 200ng/ml. Methods: This is a first in human phase 1 (3+3) dose-finding study of oral CO-1686, administered continuously in 21-day cycles. To be eligible, patients must have EGFR-mutant NSCLC and prior therapy with an EGFR TKI. Endpoints include safety, pharmacokinetics (PK), and efficacy. All patients undergo a biopsy for genotyping before starting study drug. Results: As of 18 Jan 2013, 35 patients (18/28 (64%) T790M+; 7 pending) have been treated with CO-1686. Dosing started at 150mg QD and escalated in steps to 900mg QD, 600mg BID and 400mg TID, with a maximum tolerated dose not yet reached. A recommended phase 2 dose is expected to be reached soon. Related AEs of grade 3 or higher were hypoglycaemia (n=1) and hyperglycaemia (n=1). AEs typical of WT-EGFR inhibition (rash, diarrhea) have not been observed. Dose-proportional PK was observed; plasma half-life was 4-5 hrs and at 900mg QD Cmax=3000ng/ml but trough concentrations were less than 200ng/ml. At greater than or equal to 300mg BID and TID dosing, trough concentrations can exceed 200ng/ml. At 900mg QD, 2 of 3 patients showed clinical benefit after 2 cycles of CO-1686 including one with clinically-relevant tumor shrinkage (18%) and a second with stabilization of a pleural effusion that had previously required repeat thoracenteses at ~10 day intervals. At 300mg BID, one patient (Del(19)/T790M+) with PK trough concentration greater than 200ng/ml exhibited significant tumor shrinkage (29%) after 2 cycles. Further efficacy data from BID/TID cohorts and centrally-confirmed genotypes will be presented at the meeting. Conclusions: CO-1686 offers potential for improved activity and better tolerability over current EGFR TKIs, particularly in the treatment of T790M+ disease, an area of high unmet clinical need. Curis Abstract No. 2503 Title: Phase I study of safety and pharmacokinetics (PK) of GDC-0917, an antagonist of inhibitor of apoptosis (IAP) proteins in patients (Pts) with refractory solid tumors or lymphoma. Background: GDC-0917 is a small molecule that triggers tumor cell apoptosis by selectively antagonizing IAP proteins. Preclinical studies demonstrated antitumor efficacy of GDC-0917 alone or in combination with chemotherapeutic agents. Methods: Oral GDC-0917 was given on Day (d) 1 followed by 2d off and a 2-week (w) on/ 1w off treatment (tx) schedule (21d cycle) starting d4. A modified continual reassessment method was used for dose escalation. Dose-limiting toxicity (DLT, assessed d1-24), PK, adverse events (AEs), pharmacodynamics (PD), and clinical activity were evaluated. Results: 42 pts of age 36-86 (median 60.5) were enrolled in 11 cohorts (5-600 mg) and received 1-15 cycles (median 2) of GDC-0917. One DLT, Grade (G) 3 fatigue, was observed at 450 mg. The maximum tolerated dose was not determined although plasma concentrations of preclinically defined IC90 were reached. The most frequent AEs were diarrhea, fatigue and nausea (26.2% each), vomiting (23.8%), and constipation (19%). The most frequent AEs reported as tx-related were mostly G1-2 and included fatigue and nausea (21.4% each), vomiting (14.3%), rash (11.9%) and pruritus (9.5%). AEs reported as tx-related that were greater than or equal to G3 in greater than 1 pt were elevated AST and ALT (2 pts, at 450 and 600 mg). AEs reported as tx-related that resulted in tx discontinuation were G3 fatigue, G2 QTc prolongation, G2 drug hypersensitivity, G2 pneumonitis (1 pt each), and G3 pruritus/G2 rash (same pt). GDC-0917 peak concentrations were observed 2-3h post dosing. Exposure was dose-proportional with a mean plasma elimination t1/2of 4-8h and no apparent accumulation at steady state. Rapid down-modulation of cIAP1 was observed in PBMCs at all dose levels. Evaluation of tumor biopsies demonstrated decreases in cIAP1 (2 pts total, at 40 and 200 mg) and increases in activated caspase-3 and cPARP (1 pt at 200 mg). Two pts (4.8%) had a complete response (both unconfirmed, ovarian Ca and MALT lymphoma
PET); 4 pts (9.5%) had stable disease for greater than or equal to 3 months. Conclusions: GDC-0917 had a favorable safety, PK and PD profile in pts with advanced malignancies. These encouraging results support further clinical evaluation of this agent.
Halozyme Abstract No. 4010 Title: A phase Ib study of gemcitabine plus PEGPH20 (pegylated recombinant human hyaluronidase) in patients with stage IV previously untreated pancreatic cancer. Background: PEGPH20 is a PEGylated version of human recombinant hyaluronidase. In preclinical studies, PEGPH20 depleted pancreatic cancers of their high hyaluronan (HA) content. In a genetically-engineered murine model of PDA, PEGPH20 + gemcitabine (Gem) significantly prolonged survival compared to Gem alone. In Ph1 PEGPH20 monotherapy studies, the MTD was 3.0 ug/kg. The most common AEs were musculoskeletal events (MSEs). Methods: This was a dose-escalation study to find the recommended Phase 2 dose (RP2D) of PEGPH20 in combination with Gem in patients (pts) with Stage IV previously untreated pancreatic cancer. Pts received PEGPH20 at 1, 1.6, or 3 ug/kg IV twice a week for Wks 1-4, weekly for Wks 5-7, then 1 wk rest. Dose escalation was based on safety. Gem was given at 1000 mg/m2 IV once a week for Wks 1-7, then 1 wk rest. Thereafter, PEGPH20 + Gem were given once a week for 3 wks in 4-wk cycles. Dexamethasone was given pre and post PEGPH20 doses. Results: Of the 28 pts enrolled, the majority had a Karnofsky performance status of 80%, and 85%/19%/26% of pts had liver/lung/visceral metastases. The median age was 58 yrs. Four pts received PEGPH20 at 1 ug/kg, 4 at 1.6 ug/kg, and 20 at 3 ug/kg. The RP2D was 3 ug/kg. Treatment duration ranged from 1-274 days; 5 pts remain on study. Treatment was generally well tolerated. Ten pts had 1 Gem dose reduction, 2 pts had 1 PEGPH20 dose reduction (3 to 1.6 ug/kg), but no pt had a DLT. The most common PEGPH20-related AEs were MSEs (25% Gr1; 18% Gr2) and fatigue (21% Gr1; 11% Gr2). Objective response was assessed by an independent central radiologist using RECIST 1.1. Of the 21 pts evaluable for efficacy, 7 had partial response (PR) for an overall response rate (ORR) of 33%, and 9 had stable disease for greater than or equal to 2 mo. Tumor biopsies from 12 pts were evaluable for HA staining. HA was high in 9 and low in 3. Of the 9 with high HA staining, 5 had PR (56% ORR); HA data were not available for the other 2 PR pts. PK results show dose-dependent exposure consistent with data from PEGPH20 monotherapy studies. Conclusions: PEGPH20 in combination with Gem is generally well tolerated in advanced pancreatic cancer and shows promising efficacy, especially in pts with high intratumoral HA content. Infinity Pharmaceuticals Abstract No. 8518 Title: Preliminary safety and efficacy of IPI-145, a potent inhibitor of PI3-K delta, gamma in patients with relapsed/refractory lymphoma. Background: Phosphoinositide-3-kinases (PI3Ks) are pivotal in cell signaling and regulate a variety of cellular functions relevant to oncogenesis. IPI-145, a potent oral inhibitor of the PI3K delta and PI3K gamma isoforms, is in clinical development for patients (pts) with hematologic malignancies. Early results in pts with relapsed/refractory lymphoma from an ongoing Phase 1 study are reported here. Methods: This dose-escalation study evaluates the safety, maximum tolerated dose (MTD), clinical activity, and pharmacokinetics (PK) of IPI-145. Expansion cohorts (EC) less than MTD are allowed. IPI-145 is given orally twice daily (BID) in 28-day cycles. Tumor response is based on standard disease-specific criteria. Results: 55 pts have been dosed with IPI-145. PK, available through 50 mg BID, are linear with complete inhibition of PI3K-delta at doses greater than 15 mg BID and increasing suppression of PI3K-gamma with increasing dose. In the 36 pts with lymphoma who received 15 mg to 75 mg BID, the median
range number of cycles was 2.4 0.1-10 and 67% remain on study. Treatment-related adverse events (TRAEs) occurred in 50% of pts with lymphoma. Neutropenia and increased ALT were the most common greater than or equal to Grade 3 TRAEs (4 pts each) and were not associated with increasing dose. Greater than Grade 3 ALT elevations were more common in lymphoma pts (18%) compared to non-lymphoma pts (5%). Among evaluable pts with lymphoma (n=27), early clinical activity was observed in T-cell (n=6, 1 CR, 1 PR, 1 SD) and aggressive/indolent B-cell (n=21, 2 CR, 9 PR, 5 SD) lymphoma pts at less than or equal to 75 mg BID. 92% of responses were observed by 3 months. Conclusions: IPI-145 appeared well tolerated and has shown clinical activity in pts with relapsed/refractory advanced B- and T-cell lymphoma across the range of doses examined. The single agent MTD has not been determined and dose escalation continues. Updated safety and efficacy data from pts with lymphoma enrolled in dose escalation or ECs evaluating 25 mg BID and a higher dose (less than MTD) of IPI-145 will be presented.
Pharmacyclics and Johnson & Johnson Abstract No. 8502 Title: Phase Ib study combining ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with CD20-positive B-cell non-Hodgkin lymphoma (NHL). Background: Ibrutinib, a first-in-class oral Bruton's tyrosine kinase inhibitor, has demonstrated single-agent activity in a variety of relapsed or refractory B-cell malignancies with limited toxicity, making it an appropriate drug to combine with standard R-CHOP chemotherapy in patients with previously untreated NHL. Methods: Patients received oral daily dose of ibrutinib (280, 420, or 560 mg) in combination with standard doses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, and vincristine on day 1, and prednisone on days 1 through 5 of each 21-day cycle for up to 6 cycles). The primary objective was to determine the recommended phase 2 dose (RP2D) of ibrutinib in combination with standard R-CHOP (IR-CHOP). The secondary objectives were to assess safety, overall response rate, pharmacokinetics, and pharmacodynamic biomarkers. Results: Seventeen patients (7, 4, and 6 in increasing ibrutinib doses) were enrolled: 59% male, median age 65 (range 46-81) years, diffuse large B-cell lymphoma 47%, mantle cell lymphoma 29% and follicular lymphoma 24%. In the 280 mg cohort, 2 patients had dose-limiting toxicity (DLT): 1 with transient syncope and 1 with periorbital cellulitis; at 560 mg, 1 patient had gastritis (grade 2). The RP2D was established at 560 mg ibrutinib. The most common (greater than or equal to 20% of patients) adverse events (AEs) were neutropenia (77%), thrombocytopenia (65%), vomiting (59%), anemia (53%), nausea (47%), fatigue (35%), headache (29%), constipation (24%), diarrhea (24%), and dizziness (24%). To date, 6 patients completed 6 cycles of treatment, and 2 patients discontinued treatment (1 due to noncompliance with the study drug and 1 due to non-DLT AE). At the time of this analysis, of the 10 patients had at least one post baseline tumor, the overall response rate was 100% (7 complete and 3 partial responses). Conclusions: The combination of IR-CHOP has an acceptable safety profile. No new toxicities were noted with adding ibrutinib to R-CHOP. An expansion cohort 560 mg ibrutinib (RP2D) is being opened to further explore the safety and efficacy of IR-CHOP in patients with newly diagnosed diffuse large B-cell lymphomas. -- Reported by Adam Feuerstein in Boston. Follow @AdamFeuerstein