ALBERT

Description: Introduction: Continuous treatment with lenalidomide (len) is a new standard of care in frontline multiple myeloma (MM) (Facon. Blood. 2018;131:301-310; Pulte. Oncologist. 2018;23:734-739). The increased adoption of continuous len treatment and len maintenance highlights the need for active regimens for the treatment of MM that has relapsed or become refractory to len. Once-weekly carfilzomib (K) at 70 mg/m2 (Berenson. Blood. 2016;127:3360-3368; Moreau. Lancet Oncol. 2018;19:953-964) and twice-weekly K at 56 mg/m2 (Dimopoulos. Lancet Oncol. 2016;17:27-38) in combination with low-dose dexamethasone (d) have shown a favorable benefit-risk profile for the treatment of relapsed and/or refractory MM. This post-hoc analysis will assess the efficacy and safety of Kd in len exposed and refractory MM. Methods: Individual patient data from the phase 1/2 CHAMPION-1 (CH-1), phase 3 ENDEAVOR, and phase 3 ARROW studies were pooled to evaluate progression-free survival (PFS), overall response rate (ORR), and safety for those with previous exposure or refractoriness to len treatment. The once-weekly Kd dosing schedule in CH-1 (Berenson. Blood. 2016;127:3360-3368) and ARROW (Moreau. Lancet Oncol. 2018;19:953-964) and the twice-weekly Kd dosing schedule in ENDEAVOR (Dimopoulos. Lancet Oncol. 2016;17:27-38) have been previously described. Patients who received once-weekly Kd at 70 mg/m2 in CH-1 and ARROW, and patients who received twice-weekly Kd at 56 mg/m2 from ENDEAVOR were included in the analysis. Patients were assigned to a group according to prior lines of therapy and previous len exposure: (1) combined CH-1 and ENDEAVOR patient population (N=39) that had received 1 prior line of therapy and was previously exposed but not refractory to len (Kd, 1 prior len exposed); (2) combined CH-1 and ENDEAVOR patient population (N=32) that had received 1 prior line of therapy and was refractory to len in the last line of therapy (Kd, 1 prior len refractory); (3) combined CH-1, ENDEAVOR, and ARROW patient population (N=65) that had received 2 to 3 prior lines of therapy and was exposed but not refractory to len (Kd, 〉1 prior len exposed); (4) combined CH-1, ENDEAVOR, and ARROW patient population (N=304) that had received 2 to 3 prior lines of therapy and was refractory to len in any line of previous therapy (Kd, 〉1 prior len refractory). Results: PFS, ORR, and safety outcomes in the pooled len exposed and refractory patient populations are shown (Table 1). Len-exposed patients treated with Kd in first relapse had a median PFS of 18.3 months (95% confidence interval [CI] 14.1-21.0); PFS rate at 18 months was 54.0%. When len-refractory patients were treated with Kd in first relapse, median PFS was 15.6 months (95% CI 9.6-not estimable [NE]) and the PFS rate at 18 months was 43.1%. For len-exposed patients treated in second or third relapse, the median PFS for Kd was not reached (95% CI 10.3-NE) and PFS rate at 18 months was 57.1%. For len-refractory patients treated with Kd in second or third relapse, median PFS was 8.8 months (95% CI 7.5-11.2) and the PFS rate at 18 months was 27.8%. ORR was approximately 90% (Kd, 1 prior len exposed), 81% (Kd, 1 prior len refractory group), 77% (Kd, 〉1 prior len exposed), and 61% (Kd, 〉1 prior len refractory). Median K treatment duration (range) was 56.0 (4.0-213.0) months (Kd, 1 prior len exposed), 36.6 (1.0-201.1) months (Kd, 1 prior len refractory), 36.1 (1.1-210.7) months (Kd, 〉1 prior len exposed), and 34.0 (0.1-198.0) months (Kd, 〉1 prior len refractory). The incidence of treatment-emergent grade ≥3 adverse events (AEs) was 84.6% for patients in the Kd, 1 prior len-exposed group, 81.3% for patients in the Kd, 1 prior len-refractory group, 76.9% for patients in the Kd, 〉1 prior len-exposed group, and 74.8% for patients in the Kd, 〉1 prior len-refractory group. The rate of serious AEs in each of the pooled patient groups in this analysis is presented (Table 1). Conclusion: The Kd doublet is effective and safe in MM patients relapsing on or after treatment with len, and for patients who are refractory to len. Although data are limited by small sample size, the median PFS of 15.6 months for Kd in len-refractory patients treated in first relapse is similar in magnitude to the median PFS reported for novel triplet therapy in this population. Disclosures Mateos: Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Berdeja:Genentech: Research Funding; Bluebird: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Glenmark: Research Funding; Novartis: Research Funding; Teva: Research Funding; Sanofi: Research Funding; Poseida Therapeutics, Inc.: Research Funding. Dimopoulos:Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Siegel:Takeda: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Ho:Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria, Other: travel to meeting; Celgene: Other: travel to meeting. Huang:Amgen: Employment, Equity Ownership. Sersch:Amgen: Employment. Zahlten-Kumeli:Amgen: Employment, Equity Ownership. Kimball:Amgen: Employment, Equity Ownership; WindMIL Therapeutics: Equity Ownership. Weisel:Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene, Janssen, and Sanofi: Research Funding.

Description: In ENDEAVOR, carfilzomib (56 mg/m2) and dexamethasone (Kd56) demonstrated longer progression-free survival (PFS) over bortezomib and dexamethasone (Vd) in patients with relapsed/refractory multiple myeloma (RRMM). Here we evaluated Kd56 vs Vd by baseline renal function in a post hoc exploratory subgroup analysis. The intent-to-treat population included 929 patients (creatinine clearance [CrCL] ≥15 to

Description: Introduction Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor outcome and few achieve durable remission. DA-EPOCH-R (dose-adjusted cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone with rituximab) is a regimen recommended by the NCCN guidelines for untreated and R/R DLBCL. The immunomodulator, lenalidomide, and the Bruton's tyrosine kinase inhibitor, ibrutinib, have both shown single-agent efficacy in non-germinal center B-cell-like (non-GCB) DLBCL, which is enriched for the activated B-cell [ABC] subtype, and are synergistic in vitro against ABC DLBCL. This nonrandomized, multicenter, open-label study is designed to evaluate the efficacy of ibrutinib in combination with lenalidomide and DA-EPOCH-R in subjects with R/R DLBCL. Part 1 of the study is designed to determine the maximum tolerated dose (MTD) of ibrutinib and lenalidomide with DA-EPOCH-R in R/R DLBCL. In Part 2, the efficacy of this combination will be evaluated in R/R ABC DLBCL. Here, we report the results of Part 1. Methods For Part 1, patients aged ≥18 years with pathologically confirmed R/R DLBCL were enrolled. The dose-escalation phase was conducted using a standard 3+3 design. Ibrutinib was administered at a fixed dose of 560 mg (Days 1-7) and lenalidomide was dose-escalated at doses of 0, 15, 20 and 25 mg (Dose Levels 1-4, respectively) and administered on Days 1-7 of each 21-day cycle. DA-EPOCH-R was given at standard doses. Treatment was continued in 21-day cycles for up to 6 cycles. The dose-limiting toxicity (DLT) assessment period was defined as the first 22 days of dosing (Day 1 of Cycle 1 through Day 1 of Cycle 2 [predose]). The primary endpoints were the MTD and safety and tolerability of the combination regimen; the secondary endpoint was overall response rate (ORR). Results Fifteen patients (13 male) were enrolled in Part 1. Median age was 58 years (range, 38-89) with 4 (27%) patients aged ≥65 years. Median time from initial diagnosis to first dose was 17.4 months (range, 7.4-65.5). Seven (47%) patients each had GCB and non-GCB DLBCL (subtype not reported for 1 patient). At baseline, 13 (87%) patients had stage III/IV disease; 8 (53%) had bulky disease ≥5 cm (2 〉10 cm), and 10 (67%) were refractory to their last treatment. Patients had received a median of 3 prior regimens (range, 1-5). Dose escalation was completed through Dose Level 4. One DLT of diffuse alveolar damage was seen at the highest dose of lenalidomide tested. The MTD was not reached. Subjects in Part 2 will be treated with ibrutinib (560 mg) and lenalidomide (25 mg) on Days 1-7 combined with standard DA-EPOCH-R. Grade ≥3 adverse events (AEs) occurred in 14 (93%) patients. The most common grade ≥3 AEs (occurring in 〉20% of patients) were anemia (60%), febrile neutropenia (47%), leukopenia (40%), neutropenia (40%), thrombocytopenia (40%), hypokalemia (40%), and hypotension (33%). Serious AEs (SAEs) occurred in 14 patients (93%) including 2 cases (13%) of grade 2 atrial fibrillation. In 10 response evaluable patients (with at least one post-baseline radiological assessment), 2 patients had complete response (CR), 3 had partial response (PR), 2 patients had best response of stable disease, and 3 had progressive disease; 4 (67%) of 6 response evaluable non-GCB patients achieved objective response (CR/PR). Three patients continue treatment, 2 patients completed the protocol-specified treatment, and 10 patients discontinued treatment. Reasons for treatment discontinuation included AEs (n=3), progressive disease (n=3), stem cell transplant after achieving CR/PR (n=2), disease worsening (n=1), and death (n=1). Enrollment into Part 2 of the study has been initiated at Dose Level 4. Conclusions The Part 2 dose was established as 560 mg ibrutinib and 25 mg lenalidomide combined with standard DA-EPOCH-R. Ibrutinib in combination with lenalidomide and DA-EPOCH-R showed acceptable safety and tolerability and promising anti-tumor activity in patients with R/R DLBCL. The efficacy of this combination regimen will be further evaluated in Part 2 of this trial. Disclosures Off Label Use: yes; ibrutinib and lenalidomide in relapsed/refractory DLBCL. Phillips:Incyte: Other: Travel, Accommodations, Expenses. Ping:Pharmacyclics LLC, an AbbVie Company: Employment. Neuenburg:Pharmacyclics LLC, an AbbVie Company: Employment. Cavazos:Pharmacyclics LLC, an AbbVie Company: Employment. Staudt:NIH: Patents & Royalties; Pharmacyclics LLC, an AbbVie Company: Patents & Royalties, Research Funding.

Description: Introduction: Carfilzomib is an irreversible second-generation proteasome inhibitor that is currently approved for the treatment of relapsed or refractory multiple myeloma (MM). The primary objective of the CHAMPION-2 study was to determine the maximum tolerated dose (MTD) of carfilzomib when used with cyclophosphamide and dexamethasone (KCyd) for newly diagnosed MM, and secondary objectives were to evaluate the overall response rate (ORR), time to response (TTR), and safety of KCyd. Methods: This was a multicenter, open-label, single-arm, phase 1b study that enrolled patients 18 years or older with newly diagnosed symptomatic MM. Patients deferring transplant and transplant-ineligible patients were allowed. Treatment was given in 28-day cycles and continued for 8 cycles, or until unacceptable toxicity, withdrawal of consent, or progressive disease. A traditional 3+3 dose escalation scheme was used to determine the MTD of carfilzomib, with the following dose levels evaluated: 36, 45, and 56 mg/m2. Carfilzomib (30-minute infusion) was administered on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle, beginning with 20 mg/m2 on days 1 and 2 of cycle 1, then stepping up to the assigned dose level. In each cycle, cyclophosphamide (oral, 300 mg/m2) was administered on days 1, 8, and 15, and dexamethasone (oral or intravenous, 40 mg) was administered on days 1, 8, 15, and 22. An expansion cohort was enrolled at the established MTD or the maximum planned dose (MPD). Results: There were no dose-limiting toxicities observed at any of the dose levels evaluated, and thus the MPD of 56 mg/m2 was brought forward into dose expansion. A combined total of 16 patients (dose escalation + dose expansion) received carfilzomib at 56 mg/m2. The median age of patients who received KCyd at 56 mg/m2 was 65 years (range, 49-81), 56.3% were male, and 93.8% had an ECOG performance status of 0 or 1. At 56 mg/m2,the ORR was 87.5% (95% CI, 61.7%-98.4%), and best overall responses were complete response (n = 1); very good partial response (n = 7); partial response (n = 6); and stable disease (n = 2). The median TTR for patients who received the 56 mg/m2 dose and achieved partial response or better was 1 month. At 56 mg/m2,the most common adverse events of any grade were nausea (68.8%), cough (62.5%), diarrhea (56.3%), anemia (50.0%), fatigue (50.0%), and headache (43.8%), and the most common grade ≥ 3 adverse events were anemia (25.0%), hypokalemia (18.8%), neutropenia (18.8%), acute kidney injury (12.5%), and decreased white blood cell count (12.5%). Any-grade peripheral neuropathy was reported for 1 patient treated with the 56 mg/m2 dose. The mean number of treatment cycles started among patients who received the 56 mg/m2 dose was 7 (range, 3-8). In total, 6 of the 16 patients who received carfilzomib at 56 mg/m2 did not complete the 8 cycles of study treatment: 1 patient discontinued due to progressive disease (which manifested during a break in treatment for renal insufficiency), 1 patient withdrew from the study, and 4 patients discontinued treatment because of adverse events. Adverse events that led to treatment discontinuation were acute renal failure (n = 1), creatinine increase and dehydration (n = 1), intermittent nausea (n = 1), and urinary tract infection (n = 1). One patient in the 45 mg/m2 cohort experienced death due to sudden cardiac arrest; no deaths in the 36 or 56 mg/m2 cohorts occurred during the study. Conclusions: Carfilzomib administered at 56 mg/m2 twice weekly in combination with cyclophosphamide and dexamethasone was effective and showed acceptable toxicity for treating patients with newly diagnosed MM. The CHAMPION-2 study suggests that KCyd may be considered for first-line treatment of MM, including for patients not eligible for transplant. Acknowledgments: This study was supported by Onyx Pharmaceuticals, Inc. an Amgen, Inc. subsidiary. The authors would like to thank Jesse Potash of Amgen, Inc. for medical writing assistance. Disclosures Boccia: Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen/Onyx: Consultancy, Honoraria, Speakers Bureau; Genentech: Consultancy, Honoraria, Speakers Bureau; Gilead: Speakers Bureau; Eisai: Consultancy, Honoraria, Speakers Bureau. Conkling:USOncology Research: Research Funding; Amgen Inc.: Research Funding. Harb:Amgen Inc.: Consultancy. Yang:Amgen Inc.: Employment, Equity Ownership. Pinchasik:Amgen Inc.: Employment, Equity Ownership. Kimball:Amgen Inc.: Employment, Equity Ownership. Berenson:OncoTracker: Employment, Equity Ownership.

Description: Background: The combination of carfilzomib with lenalidomide and dexamethasone (KRd) is approved in the United States and the European Union (EU) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). Under these approvals, carfilzomib is administered twice weekly as a 10-minute intravenous (IV) infusion at a dose of 20/27 mg/m2. The phase 1/2 CHAMPION-1 study showed that once-weekly carfilzomib (20/70 mg/m2; 30-minute IV infusion) with dexamethasone was well tolerated and active in patients with RRMM (Berenson et al. Blood. 2016;127:3360−3368). We present initial results from the dose evaluation component of a phase 1b study (NCT02335983) assessing the safety and efficacy of once-weekly carfilzomib with lenalidomide and dexamethasone in patients with MM. Methods: This is an open-label, multicenter, dose-finding, phase 1b study.The primary objective of the study is to evaluate the safety and tolerability of a once-weekly KRd regimen. Secondary objectives included evaluation of the efficacy of a once-weekly KRd regimen. This study consists of 2 parts: a dose-evaluation component in patients with RRMM and a dose-expansion component in both RRMM and newly diagnosed MM (NDMM). Results from the ongoing dose-evaluation component in RRMM are presented. There were 2 planned dose cohorts in the dose-evaluation portion of the study: carfilzomib 56 mg/m2 KRd cohort (56 mg/m2) and carfilzomib 70 mg/m2 KRdcohort (70 mg/m2). All patients received carfilzomib (days 1, 8, and 15), lenalidomide 25 mg (days 1 - 21), and dexamethasone 40 mg (days 1, 8, 15 and 22) on a 28-day cycle (dexamethasone was not administered on day 22 for cycles 9+). Carfilzomib was administered as a 30-minute IV infusion: 20 mg/m2 on cycle 1 day 1 with escalation to the assigned dose level (56 or 70 mg/m2) thereafter. The protocol allowed 8 DLT-evaluable patients to be treated in the 56 mg/m2 and 70 mg/m2 cohorts. Response was assessed by investigators using International Myeloma Working Group Uniform Response Criteria. The data cutoff date for this analysis was June 23, 2016. Results: A total of 22 patients (56 mg/m2, n=10; 70 mg/m2, n=12) with a median age of 69 (range, 50-87) years were enrolled in the dose evaluation component of the study. The median number of prior regimens was 1 (range, 1 - 3) in both cohorts. There were no dose-limiting toxicities observed in any of the 15 dose-evaluable RRMM patients (56 mg/m2 cohort, n=8; 70 mg/m2 cohort, n=7). The median number of cycles started as of data cutoff was 9.5 (range, 3-15) in the 56 mg/m2 cohort and 6.0 (range, 2-9) in the 70 mg/m2 cohort. All patients experienced at least 1 treatment-emergent adverse event (AE). Grade ≥3 AEs occurring in ≥9% of patients, and any AE of interest are shown in Table 1. The only grade ≥3 AEs to occur in ≥2 patients (≥9%) were thrombocytopenia (56 mg/m2, n=2; 70 mg/m2, n=1), decreased neutrophil count (56 mg/m2, n=2; 70 mg/m2, n=1), anemia (56 mg/m2, n=2), and hypertension (56 mg/m2, n=1; 70 mg/m2, n=1). Although the numbers were small, there was no apparent difference in the incidence of dyspnea or hypertension between the 56 and 70 mg/m2 cohorts. Cardiac or renal failure of any grade was not reported at the time of the database snapshot in these patients with RRMM. Response rates after 4 cycles, as assessed by investigators, are shown in Table 2. Two patients in the 56 mg/m2 cohort did not complete 4 cycles: an 87-year old patient developed asymptomatic pulmonary hypertension (detected on a required echocardiogram study) and was taken off therapy; another patient withdrew consent. One patient in the 70 mg/m2 cohort had a partial response after cycle 1 but was found to have progressive disease in cycle 3 (listed as did not complete 4 cycles in Table 2). After 4 cycles, the response rates (investigator assessed), were 70% and 75% in the 56 and 70 mg/m2 cohorts (response assessment for 2 patients in the 70 mg/m2 cohort was missing at the time of the data cutoff). Conclusions: These results demonstrate that carfilzomib administered in a convenient once-weekly schedule in combination with lenalidomide and dexamethasone in patients with RRMM is safe with promising efficacy. The 70 mg/m2 dosing was selected for dose-expansion cohorts in RRMM and NDMM. An update on the expansion cohorts will be presented at the meeting. Disclosures Biran: Onyx: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Siegel:Novartis: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Merck: Honoraria; BMS: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding. Faber:Celgene: Speakers Bureau; Cardinal Health: Honoraria; Gilead: Consultancy, Honoraria. Seneviratne:Novartis Pharmaceuticals: Speakers Bureau. Alsina:Onyx: Speakers Bureau; Millenium Pharmaceuticals: Research Funding; Novartis: Research Funding; Signal Genetics: Consultancy; Onyx: Consultancy. Bensinger:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau. Kimball:Amgen Inc.: Employment, Equity Ownership. Zhou:Amgen Inc.: Employment, Equity Ownership. Landgren:BMS: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

Description: Background Targeting the PI3K/Akt/mTOR axis in relapsed lymphomas is of interest based on constitutive activation in many lymphoma subtypes, and has had varying degrees of success. We previously showed that the first generation mTOR inhibitor, temsirolimus (TEM), has activity across histologies with an acceptable toxicity profile (Smith, et al., JCO 2010). Lenalidomide (LEN) is currently approved for use in indolent non-Hodgkin lymphomas, and has several potential synergistic and overlapping targets with PI3K/mTOR/Akt inhibition. We designed this phase I/II clinical trial to evaluate the efficacy and tolerability of the combination of TEM and LEN in relapsed/refractory lymphomas. Methods The phase I dose-finding study utilized a standard "3+3" design and was open to all patients with mature B-cell malignancies. TEM was 25 mg IV weekly for all dose levels. LEN was dosed orally on D1-D21 every 28 days at three dose levels: 15 mg, 20 mg, and 25 mg. The phase II study accrued patients in a two-stage "minimax" design with stratification into three histologically-defined cohorts: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and other lymphomas. Primary endpoints of the phase II study were rates of complete (CR) and overall response (ORR), and secondary endpoints were duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results In the phase I study, 18 patients were enrolled and available for toxicity assessment. Patients were treated to intolerance, progression, or discontinuation at physician discretion. Of these, 15 patients were evaluable for dose-limiting toxicity (DLT) assessment. At dose level 3, there were 2 DLTs: grade 3 diarrhea and grade 3 HSV mucositis. Dose level 2 was thus established as the recommended phase II dose: TEM 25 mg weekly and LEN 20 mg on D1-D21 every 28 days. Of the 18 patients, there were 5 partial responses, 4 stable disease, 3 progressive disease, 4 on active treatment, and 2 not adequately assessed. The phase II study enrolled an additional 93 patients (Table 1): 39 DLBCL, 15 FL, and 39 other lymphomas which included 20 relapsed/refractory Hodgkin lymphoma (HL) patients. The median number of prior treatments was 4 (range, 1-14), and 31 patients (33%) had relapsed following prior autologous stem cell transplantation (ASCT). The median number of cycles delivered was 4 (range, 1-21). The FL cohort closed prematurely due to slow accrual. The ORR were 25.6% (12.8% CR) and 64.1% (17.9% CR) for DLBCL and other lymphoma cohorts, respectively (Table 2). The ORR for HL patients in the other lymphoma cohort, the majority of whom had relapsed after brentuximab vedotin (BV) and autologous stem cell transplantation (ASCT), was 80% (35% CR). Eight HL patients (40%) proceeded to allogeneic transplantation after TEM and LEN therapy. The high response rate in the other lymphoma cohort was sufficient to reject the null hypothesis of a 30% response rate under the minimax design. Median PFS was 7.0 mo (90% CI 3.5-8.0) and 7.0 mo (90% CI 4.6-9.9) for DLBCL and other lymphoma cohorts, respectively (Table 2). Median OS was 9.1 mo (90% CI 6.0-16.0) and 25.5 mo (90% CI 10.8-60.6) for DLBCL and other lymphoma cohorts, respectively (Table 2). Median DOR was 13.8 mo (90% CI 4.1-19.0) and 5.5 mo (90% CI 2.6-23.7) for DLBCL and other lymphoma cohorts, respectively (Table 2). Median PFS, OS and DOR for HL patients in the other lymphoma cohort were 9.2 mo (90% CI 4.6-25.5), 39.6 mo (90% CI 17.4-NR), and 8.1 mo (90% CI 5.1-38.3), respectively. Kaplan-Meier curves are displayed in Figure 1. Grade ≥3 non-hematologic adverse events (AE) related to treatment were uncommon, with no cases of pneumonitis and one grade 3 thromboembolism. Grade ≥3 hematologic AEs were common and reversible. Three Grade 5 AEs occurred (colonic perforation, myocardial infarction and sepsis). Conclusions Combination therapy with TEM and LEN demonstrated encouraging activity in heavily-pretreated and relapsed/refractory lymphomas. Survival in the other lymphoma cohort was primarily driven by favorable activity in relapsed/refractory HL. TEM and LEN may be a suitable option for treatment of HL after BV and ASCT, including as a bridge to allogeneic stem cell transplantation. Further study of PI3K/Akt/mTOR inhibition in combination with lenalidomide is warranted, particularly in relapsed HL. Disclosures Kline: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Kite/Gilead: Speakers Bureau. Kimball:Amgen: Current Employment; Amgen: Current equity holder in publicly-traded company. Petrich:Daiichi-Sankyo: Current Employment; AbbVie: Current equity holder in publicly-traded company. Smith:Celgene: Consultancy, Research Funding; Janssen: Consultancy; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; TG Therapeutics: Consultancy, Research Funding; FortySeven: Research Funding; Pharmacyclics: Research Funding; Karyopharm: Consultancy, Research Funding; BMS: Consultancy; Acerta: Research Funding. OffLabel Disclosure: Temsirolimus is FDA-approved for renal cell carcinoma.