Forero‐Torres, Andres

Abstract BACKGROUND: SGN-40 is a humanized monoclonal antibody that targets CD40. Upon binding to CD40, SGN-40 triggers pro-apoptotic signal transduction pathways and mediates effector cell functions (ADCC and ADCP). SGN-40 demonstrated preliminary anti-tumor activity in a phase 1 study of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL) patients (ASH 2006, Abstract 695). METHODS: We conducted a multicenter, phase 2, open-label study to determine the overall response rate and toxicity profile of SGN-40 in patients with relapsed DLBCL. Tumor samples were assessed by a central lab for pathology confirmation and CD40 expression. Eligible patients had de novo or transformed DLBCL at diagnosis and were excluded if previously treated for indolent lymphoma. Required prior therapy consisted of combination chemotherapy with rituximab and, if eligible, autologous stem cell transplantation. Patients received 6 intravenous infusions of SGN-40 over 5 weeks (Cycle 1) with intra-patient dose loading (1 mg/kg on Day 1; 2 mg/kg on Day 4; 4 mg/kg on Day 8) and 8 mg/kg/wk thereafter. Responding patients and those with stable disease were eligible to continue therapy until disease progression or a maximum of 12 cycles. RESULTS: Forty-six patients (28 M, 18 F), with a median age of 72 years (range 17–85), were enrolled at 10 centers in the US. Patients were heavily pre-treated, with a median of 4 prior systemic chemotherapy regimens (range 1–10). Immunohistochemistry analysis of patient tumor samples demonstrated high expression of CD40 in all patients with the exception of 1 patient who was negative. Thirty-eight of the 46 patients met predefined criteria for evaluation (completed dose loading and had no major protocol violations). Best responses seen were CR (n=2, 5%) and PR (n=2, 5%), yielding an ORR of 10%. Furthermore, 9 (24%) patients had SD as best response. Reductions in tumor size were seen in approximately one-third of patients. Twenty (53%) patients had PD and 5 (13%) patients have yet to be assessed. Treatment with SGN-40 was generally well tolerated. Grade 3/4 events that occurred in more than 1 patient in the intent-to-treat population (N=46), regardless of drug attribution were thrombocytopenia (n=5); neutropenia (n=4); and anemia, fatigue, pneumonia, hyponatremia, DVT, and disease progression (n=2 pts each). Of these events, only fatigue (n=2) and neutropenia (n=2) were considered drug related by the investigator. CONCLUSION: Monotherapy with SGN-40 in DLBCL patients is well tolerated and resulted in objective responses consistent with the previous phase 1 experience. These data support further evaluation of SGN-40 in combination with chemotherapy in non-Hodgkin lymphoma; 3 combination clinical trials are ongoing. Retrospective correlation of clinical outcome and a gene signature that includes baseline CD40 activation status are planned.

1052 Background: TIG, an agonistic anti-DR5 monoclonal antibody, triggers apoptosis in DR5+ human tumor cells without the aid of crosslinking. TIG has shown strong in vitro and in vivo activity against basal-like breast cancer cells that is enhanced by chemotherapy like paclitaxel. Methods: Randomized 2:1 phase II trial of nab-PAC with/without TIG in TNBC patients. Patients stratified by prior exposure to chemotherapy in the metastatic setting. Patients received nab-PAC weekly x 3 and TIG every other week, every 28 days. Primary endpoint was overall response rate (ORR). Secondary objectives were safety, progression free survival (PFS), TIG immunogenicity, and PK. Biopsies and circulating tumor cells were collected. The trial was not powered to compare arms but allowed early stopping for futility and was sized to estimate ORR with 95% CI. Results: 64 patients enrolled, 60 treated; 39 in the combination arm and 21 in the nab-PAC arm. Of the 39 in the combination arm, there were 2 CR, 9 PR (1 near CR, 96% tumor reduction), 11 SD and 17 PD; ORR 28% (95% CI 14%-42%). Of the 21 in the single agent arm, there were no CR, 8 PR, 4 SD and 9 PD; ORR 38% (95% CI 17%-59%). Higher ORRs were seen in the chemotherapy naïve patients (58% vs. 15% combination and 42% vs. 35% single agent). 2 patients with CR, 1 near CR, and 1 PR in the combination arm are still on therapy (602+, 531+, 466+, 460+ days). PFS was similar in both groups (3.6 months); higher in chemotherapy naïve patients. Combination was well tolerated (most toxicities grade 1/2); the most common AEs were fatigue, alopecia, peripheral sensory neuropathy, anemia, neutropenia, nausea, thrombocytopenia, anorexia, diarrhea, and vomiting. No grade 4 or 5 toxicity. No apparent added toxicity with TIG was seen. Conclusions: Combination therapy with nab-PAC + TIG was well tolerated, without apparent improvement in ORR relative to nab-PAC alone; however, 4 subjects treated as first-line had prolonged clinical benefit with the combination, and correlative studies will investigate markers that might predict clinical outcome (Next-Gen genomic analysis). Clinical trial information: F101004001.

1006 Background: Patients (pts) with ER-/PR- MBC do not benefit from endocrine treatment (tx). Doane et al (Oncogene 2006;25:3994) described a subset of ER-/PR- BC with a gene expression profile similar to ER+ BC but characterized by AR expression and AR-dependent growth in vitro. Hence, we conducted a multicenter phase II trial (NCT00468715) of the AR antagonist, bicalutamide (B) for pts with AR+ ER-/PR- MBC. Methods: Pts with ER-/PR- (IHC <10%) MBC were consented to AR testing, confirmed centrally at MSKCC. If AR+ (DAKO IHC ≥10%), pts were eligible for tx if ECOG performance status (PS) <2 and normal organ function. No limit on prior tx except prior trastuzumab required if HER2+. Eligible AR+ pts who consented to tx received B 150mg orally daily in 28-day cycles (C). Toxicity assessed q4wks, response q12wks. Primary endpoint = clinical benefit rate (CBR): CR + PR + stable disease (ds) >6mo (SD). B would be considered worthy of further study if ≥4/28 pts have clinical benefit. Results: As of 12/21/11,436 pts consented for AR testing. 24 were ineligible, 12 await testing. 47/400 tested were AR+ (12%). 26 received tx with B (6 ineligible for tx, 15 are eligible for tx with B at progression (POD) if clinically appropriate and study slots remains). Two AR+ pts treated with B were ER+ and removed from study. Three have received tx <12wks. Treated pt characteristics (n=24): median(med)age 64 (41-83), PS 0 (0-1), HER2+ 1, visceral metastases 17. Prior chemotherapy: neo/adjuvant 16; med # regimens for MBC 1 (0-8). Med C# 3 (2-49+). Best response: (21 evaluable pts): CBR 19% (95% CI 5-42%), SD>6mo 4, CR/PR 0, SD<6mo 3, POD 14. Conclusions: ~12% of ER-/PR- MBC pts are AR+. For these pts, AR-inhibition with B is feasible, well tolerated, and has activity based on pre-specified criteria. This study has closed to accrual for AR testing as of 1/2012. These results of the primary endpoint are not expected to change by accrual of the 2 remaining pts. Supported by TBCRC/Breast Cancer Alliance/AstraZeneca. [Table: see text]

PURPOSEThe phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin is a key pathway of survival and therapeutic resistance in breast cancer. We evaluated the pan-Akt inhibitor MK-2206 in combination with standard therapy in patients with high-risk early-stage breast cancer.PATIENTS AND METHODSI-SPY 2 is a multicenter, phase II, open-label, adaptively randomized neoadjuvant platform trial that screens experimental therapies and efficiently identifies potential predictive biomarker signatures. Patients are categorized by human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), and MammaPrint statuses in a 2 × 2 × 2 layout. Patients within each of these 8 biomarker subtypes are adaptively randomly assigned to one of several experimental therapies, including MK-2206, or control. Therapies are evaluated for 10 biomarker signatures, each of which is a combination of these subtypes. The primary end point is pathologic complete response (pCR). A therapy graduates with one or more of these signatures if and when it has an 85% Bayesian predictive probability of success in a hypothetical phase III trial, adjusting for biomarker covariates. Patients in the current report received standard taxane- and anthracycline-based neoadjuvant therapy without (control) or with oral MK-2206 135 mg/week.RESULTSMK-2206 graduated with 94 patients and 57 concurrently randomly assigned controls in 3 graduation signatures: HR-negative/HER2-positive, HR-negative, and HER2-positive. Respective Bayesian mean covariate-adjusted pCR rates and percentage probability that MK-2206 is superior to control were 0.48:0.29 (97%), 0.62:0.36 (99%), and 0.46:0.26 (94%). In exploratory analyses, MK-2206 evinced a numerical improvement in event-free survival in its graduating signatures. The most significant grade 3-4 toxicity was rash (14% maculopapular, 8.6% acneiform).CONCLUSIONThe Akt inhibitor MK-2206 combined with standard neoadjuvant therapy resulted in higher estimated pCR rates in HR-negative and HER2-positive breast cancer. Although MK-2206 is not being further developed at this time, this class of agents remains of clinical interest.

Abstract The phase 3 ECHELON-1 study demonstrated that brentuximab vedotin (A) with doxorubicin, vinblastine, and dacarbazine (AVD; A+AVD) exhibited superior modified progression-free survival (PFS) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for frontline treatment of patients with stage III/IV classical Hodgkin lymphoma (cHL). Maturing positron emission tomography (PET)-adapted trial data highlight potential limitations of PET-adapted approaches, including toxicities with dose intensification and higher-than-expected relapse rates in PET scan after cycle 2 (PET2)-negative (PET2−) patients. We present an update of the ECHELON-1 study, including an exploratory analysis of 3-year PFS per investigator. A total of 1334 patients with stage III or IV cHL were randomized 1:1 to receive 6 cycles of A+AVD (n = 664) or ABVD (n = 670). Interim PET2 was required. At median follow-up of 37 months, 3-year PFS rates were 83.1% with A+AVD and 76.0% with ABVD; 3-year PFS rates in PET2− patients aged &lt;60 years were 87.2% vs 81.0%, respectively. A beneficial trend in PET2+ patients aged &lt;60 years on A+AVD was also observed, with a 3-year PFS rate of 69.2% vs 54.7% with ABVD. The benefit of A+AVD in the intent-to-treat population appeared independent of disease stage and prognostic risk factors. Upon continued follow-up, 78% of patients with peripheral neuropathy on A+AVD had either complete resolution or improvement compared with 83% on ABVD. These data highlight that A+AVD provides a durable efficacy benefit compared with ABVD for frontline stage III/IV cHL, consistent across key subgroups regardless of patient status at PET2, without need for treatment intensification or bleomycin exposure. This trial was registered at www.clinicaltrials.gov as #NCT01712490 (EudraCT no. 2011-005450-60).

Abstract Background Long-term outcomes from autologous stem cell transplant (ASCT) in patients (pts) with relapsed/refractory (R/R) Hodgkin lymphoma (HL) are significantly better in patients who achieve a complete remission (CR) from salvage chemotherapy prior to ASCT. However, standard salvage therapy produces variable CR rates (19%-60%) and is associated with significant toxicity. Brentuximab vedotin and bendamustine are highly active when administered as single agents to pts with R/R HL (34% and 33% CR rates, respectively) and have manageable safety profiles. This phase 1/2, single-arm, 2-stage, open-label study was designed to evaluate the safety and efficacy of brentuximab vedotin in combination with bendamustine for the treatment of pts with primary refractory disease or in first relapse (ClinicalTrials.gov #NCT01874054). Methods Pts received an outpatient IV infusion of 1.8 mg/kg brentuximab vedotin on Day 1 with bendamustine on Days 1 and 2 of 3-week cycles for up to 6 cycles. Pts could undergo ASCT any time after Cycle 2 and post-transplant resume treatment with brentuximab vedotin as monotherapy for up to 16 total doses. Phase 1 was designed to determine the recommended dose of bendamustine, with an initial dose of 90 mg/m2 and a de-escalation scheme to be implemented if it exceeded the maximum tolerated dose. During phase 2, bendamustine was administered at the recommended dose in order to assess the CR rate of the combination. Response was assessed by the investigator per Cheson 2007. Enrollment is complete and long-term follow-up for PFS and OS continues. Results Fifty-five pts (56% female) with a median age of 36 yrs (range, 19-79) were enrolled. Fifty-one percent of pts had relapsed disease and 49% of pts had primary refractory disease after frontline therapy. A median of 13.8 mos (range, 3-98) had elapsed since initial diagnosis. No dose-limiting toxicities were observed in the safety cohort, thus the recommended dose of bendamustine in combination with brentuximab vedotin was 90 mg/m2. Pts received a median of 2 cycles (range, 1-6) of the combination and a median of 9 cycles (range, 1-14) of single-agent brentuximab vedotin. The main toxicity observed with the combination was infusion-related reactions (56% overall). The most common symptoms (≥10%) were pyrexia (26%), chills (20%), dyspnea and nausea (15% each), flushing (13%), and hypotension (11%). Premedication with corticosteroids and antihistamines was instituted with a protocol amendment and appeared effective. Before the amendment, 6 pts (24% of treated pts) discontinued treatment prematurely because of IRRs; post-amendment, IRRs led to treatment discontinuation for 2 pts (7%). The CR rate of the combination was 74% (39/53 pts evaluable for response) and the overall objective response rate (CR and partial remission) was 93% (49/53 pts). The CR rate was 64% and 84% for refractory and relapsed pts, respectively. Stem cell collection after first-line mobilization (G-CSF± plerixafor) was successful in 93% of pts (37/40). Median number of CD34+ cells collected was 4.1 x106 (Q1, Q3: 3.0, 5.4) in a median of 2 (range, 1-5) apheresis sessions. Median time to neutrophil and platelet engraftment was 11 days (range, 9-21) and 13 days (range, 9-39), respectively. Pts have been followed for a median of approximately 1 year from first dose (median = 418 days; range, 118-635) and approximately 10 mos (314 days; range, 13-553) from ASCT. To date, 12 progression events have been observed: 7 in the 40 pts who underwent transplant and 5 in the 13 pts who did not undergo transplant. The estimated 12-mos PFS is 80% for both the transplanted population (95% CI: 70%, 90%) and the overall population (95% CI: 60%, 90%). Three of the 12 progression events were deaths; 2 pts died from progression of their HL and 1 pt died from septic shock after transplant. Conclusions The outpatient regimen of brentuximab vedotin 1.8 mg/kg on Day 1 in combination with bendamustine 90 mg/m2 on Days 1 and 2 of 3-week cycles induced a very high CR rate that compares favorably with historical data. The regimen has a manageable safety profile, with the most significant side effect being IRRs that can be successfully managed by premedication. The estimated 12-mos PFS rate of 80% demonstrates response durability, making the combination a promising salvage regimen for pts with HL in the first relapse setting. Progression-Free Survival Figure 1. Figure 1. Disclosures Off Label Use: Brentuximab vedotin is indicated in the US for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. This study evaluates brentuximab vedotin in HL patients with primary refractory disease or in first relapse. . Sawas:Seattle Genetics, Inc.: Research Funding. Agura:Seattle Genetics, Inc.: Research Funding. Matous:Takeda Pharmaceuticals International Co.: Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Seattle Genetics, Inc.: Research Funding, Speakers Bureau. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Crosswell:KIYATEC (employment); Gilead (common stock ownership and research funding): Employment, Equity Ownership, Research Funding. Islas-Ohlmayer:Seattle Genetics, Inc.: Research Funding. Behler:Seattle Genetics, Inc.: Research Funding; Onyx Pharmaceuticals: Speakers Bureau. Cheung:Seattle Genetics, Inc.: Research Funding. Forero-Torres:Seattle Genetics, Inc.: Research Funding. Vose:Seattle Genetics, Inc.: Honoraria, Research Funding. Josephson:Seattle Genetics, Inc.: Employment, Equity Ownership. Advani:Seattle Genetics, Inc.: Research Funding; Genetech: Consultancy.

Abstract Background AFM13 is a bispecific, tetravalent NK cell-engaging antibody construct binding to CD30 on CD30+ tumor cells and CD16A on NK cells. By engaging CD16A-positive NK cells, AFM13 leads to NK cell-mediated killing of CD30-positive lymphoma cells (Reusch et al., 2014) making it an attractive agent to target classical Hodgkin lymphoma (HL). Pembrolizumab is a PD-1 blocking antibody which has shown high single-agent response rates in patients (pts) with relapsed/refractory HL (RRHL; Armand et al., 2016, Chen et al., 2017). AFM13 has shown clinical activity in RRHL as a single agent in a preceding Phase 1 study (Rothe et al., 2015). Preclinical in vivo data of the combination of AFM13 with PD-1 blockade showed synergistic activity and the potential for induction of cross-talk between innate and adaptive immunity (Zhao et al., 2016). We hypothesize that the combination of the two agents could improve outcomes in pts with RRHL. Methods This Phase 1b study is evaluating the safety and tolerability of the combination of AFM13 with pembrolizumab (Keytruda) as salvage therapy after failure of standard therapies including brentuximab vedotin (BV) in HL (NCT02665650). Pts receive escalating doses of AFM13 in combination with pembrolizumab at a dose of 200 mg flat administered every 3 weeks following a classical 3+3 design, followed by enrollment into an extension cohort at the maximum tolerated dose (MTD)/maximum administered dose (MAD). Response assessment is performed every 12 weeks by PET/CT according to the Lugano Classification (Cheson et al., 2014). The main objectives of the study is to ascertain the MTD/MAD along with the preliminary efficacy of the combination. Results As of June 29, 2018, 30 pts have been enrolled into the study. The median age is 34 years (range, 18-73), with a median of 4 (range 3-7) prior lines of therapy. All pts had relapsed or refractory disease (43% relapsed, 57% refractory) and had failed standard treatments including BV and 43% of pts (13/30) had BV as their latest therapy. Thirty seven percent (11/30) had undergone prior autologous stem cell transplantation. All 30 pts have completed the 6-week dose-limiting toxicity (DLT) observation period. Twelve pts were enrolled into the dose escalation cohorts (Cohorts 1 (n=3), 2 (n=3), and 3 (n=6)) and 18 into the Extension Cohort, with a total of 24 patients treated at the MAD (dose level 3). One DLT was observed in Cohort 3 (missing ≥25% of AFM13 during the DLT period) and another observed in the Extension Cohort (G4 infusion-related reaction; IRR). The most common related adverse events (AEs) were IRRs (80%), rash (30%), pyrexia (23%), nausea (23%), diarrhea (20%), fatigue (17%), headache (17%), increased aspartate aminotransferase (13%), and increased alanine aminotransferase (10%). Treatment related G3/4 AEs included IRRs (13%), elevated AST (3%), gastritis (3%), hypotension (3%), nausea (3%), neutropenia (3%), and vomiting (3%). The majority of IRRs were manageable with standard of care measures and did not lead to treatment discontinuations. Included in the efficacy analysis were the best response from 29 evaluable pts who had at least one post-baseline disease assessment as of the data cutoff on June 29, 2018. The overall response rate (ORR) and complete response (CR) rate for evaluable pts treated at the dose and schedule chosen for expansion (n=23; Cohort 3 and Extension Cohort) were 87% and 35% by the investigator-confirmed assessment, respectively. Independent assessment resulted in an ORR of 87% and CR rate of 39% for these pts. Updated data for all 30 patients will be presented at the meeting. Conclusions The combination of AFM13 and pembrolizumab is a well-tolerated salvage therapy in pts with RRHL. IRRs were the most frequently observed adverse events; however, most of these events were of mild or moderate severity and manageable. Both the ORR and CR rate compare favorably to monotherapy pembrolizumab in a similar RRHL population (Chen et al., 2017). The combination of AFM13 and pembrolizumab could be a potential new therapeutic option for HL patients. Disclosures Bartlett: Immune Design: Research Funding; Affimed: Research Funding; Bristol-Meyers Squibb: Research Funding; Merck & Co: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding; Forty Seven: Research Funding; Novartis: Research Funding; Novartis: Research Funding; Millennium: Research Funding; ImaginAB: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees. Chen:Affimed: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech Inc.: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck & Co., Inc.: Consultancy, Research Funding, Speakers Bureau; Millennium Pharmaceuticals: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Domingo-Domenech:Affimed: Research Funding. Forero-Torres:Affimed: Research Funding. Garcia-Sanz:Affimed: Research Funding. Devata:Affimed: Research Funding. Rodriguez Izquierdo:Affimed: Research Funding. Lossos:Affimed: Research Funding. Reeder:Affimed: Research Funding. Sher:Affimed: Research Funding. Choe-Juliak:Affimed: Employment. Prier:Affimed: Research Funding. Schwarz:Affimed: Employment. Strassz:Affimed: Employment. Alland:Affimed: Employment. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Pfizer: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Merck & Co: Research Funding; Affimed: Research Funding; Takeda: Research Funding.

Abstract Abstract 586 Background: Dacetuzumab (SGN-40), a humanized monoclonal antibody that targets CD40, mediates antitumor activity through multiple mechanisms of action, including effector cell functions (ADCC/ADCP) and direct apoptotic signal transduction. Ongoing evaluation of the molecule has led to 2 additional key findings: a gene signature that predicts sensitivity to single-agent dacetuzumab, and upregulation of the pro-apoptotic and chemosensitizing transcription factor TAp63αa when dacetuzumab is combined with rituximab (R) and gemcitabine (GEM). In prior single-agent dacetuzumab trials, several patients who were immediately treated with GEM after progressing achieved unexpected responses. These observations provided rationale for further analysis of the combination of dacetuzumab, R and GEM. Methods: A phase 1b dose-escalation study to evaluate the safety and adverse event profile of dacetuzumab, R and GEM was conducted in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Patients received dacetuzumab at cohort-specific doses of 8 or 12 mg/kg IV weekly in combination with R (375 mg/m2 IV for 1 cycle, then once/28-day cycle) and GEM (1000 mg/m2 IV weekly or biweekly) in a 3 + 3 dose-escalation scheme. A maximum number of 8 cycles was permitted. Eligible patients included those with de novo DLBCL, including transformed lymphoma and follicular grade 3, who failed potentially curative therapy. Results: Thirty-one patients with a median age of 68 years (range 29–80) were enrolled and treated in the study (3 patients in each of 3 cohorts + 22 in an expansion cohort). The median number of prior regimens was 3 (range 1–18); 10 patients (32%) had transformed histology and 4 (13%) had prior ASCT. The median number of cycles received was 3 (range 1–8), although 11 patients are still on treatment. Three patients in the first cohort required dose reduction of GEM due to transient, non-dose-limiting thrombocytopenia. The protocol was thus amended to administer GEM on a biweekly schedule. No dose-limiting toxicity was observed, and MTD was not defined. Based on pharmacokinetic modeling suggesting no significant difference in exposure between dose levels, 8 mg/kg of dacetuzumab was chosen as the dose for the expansion cohort. The combination of dacetuzumab, R and GEM was generally well tolerated. Across all cohorts, the most common adverse events (> 15%) were nausea (42%), thrombocytopenia (35%), fatigue (32%), headache (29%), anorexia (19%), dyspnea (19%), pyrexia (19%), diarrhea (16%), and neutropenia (16%), the majority of which were Grade 1 or 2. Grade 3/4 adverse events related to dacetuzumab occurred infrequently. One patient experienced Grade 3 stress cardiomyopathy that resolved; this patient had a history of congestive heart failure. One patient developed pneumonitis in the left lung and acute respiratory distress syndrome, and subsequently died due to pulmonary toxicity; this patient had received prior radiation therapy to the left chest. There was preliminary evidence of antitumor activity. Of the 28 patients with response assessments, 7 patients achieved CR, 8 PR, 7 SD, and 6 PD per investigator assessment of response, yielding an objective response rate of 54%. Of interest, 1 patient who previously failed ASCT achieved a CR and was able to undergo allogeneic transplant. To date, this patient remains in CR. Conclusion: The combination of dacetuzumab, R and biweekly GEM was generally well tolerated. Evidence of antitumor activity with this combination is encouraging as multiple responses were observed in a population with heavily pre-treated patients. Further investigation with a randomized trial is warranted to more fully characterize safety and efficacy and to determine if sensitivity to this combination correlates with the previously identified single-agent predictive gene signature. Disclosures: Forero-Torres: Seattle Genetics, Inc.: Research Funding. Off Label Use: Gemcitabine has not been FDA approved for treatment of lymphoma. Dacetuzumab is an investigational agent.. Bartlett:Seattle Genetics, Inc.: Research Funding. Nasta:Seattle Genetics, Inc.: Research Funding; Genentech: Speakers Bureau. Northfelt:Seattle Genetics, Inc.: Research Funding. Beaven:Seattle Genetics, Inc.: Research Funding. Myint:Seattle Genetics, Inc.: Research Funding. Whiting:Seattle Genetics, Inc.: Employment, Equity Ownership. Drachman:Seattle Genetics, Inc.: Employment, Equity Ownership. Moskowitz:Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding.