ALBERT

Description: Inherited deficiency of purine nucleoside phosphorylase (PNP) is associated with a profound loss of T-cells. This rare clinical condition provides a model for developing specific inhibitors of PNP as therapy for T-cell malignancies. Forodesine is a specific PNP inhibitor that raises plasma 2′-deoxyguanosine (dGuo) and intracellular dGTP levels, leading to T-cell apoptosis. The objective of this study was to determine the efficacy and safety of forodesine in patients with relapsed or refractory T-cell leukemia. Patients received IV forodesine 40 mg/m2 5 days each week (1 cycle) for a total of 6 cycles (8 cycles if dose escalation needed after cycle 2). To date, 21 patients have been treated, 19 of which are T-ALL. Results are based on available data from 13 T-ALL patients. Median number of prior regimens was 4 (range: 1–6). Overall response rate was 38%, including 3 patients with complete response (CR) (23%) and 2 patients with partial response (PR) (15%). Three patients had stable disease and 5 patients had disease progression. Time to progression (TTP) for the 3 CR patients was 80, 119, and 160+ days. One CR patient continues to receive treatment. TTP for the 2 PR patients was 89 and 40 days. Plasma dGuo was elevated in all patients (range: 3.4 to 88.5 μM; predose levels ≤0.004 μM). Treatment was well tolerated. One serious adverse event possibly drug related was CMV pneumonitis in 1 patient. The most common adverse events possibly drug related were nausea (33%), headache (26%), anemia (20%), thrombocytopenia (20%), and weakness (20%). In 1 patient, after 2 doses of forodesine, WBC count dropped dramatically, requiring interruption of treatment for 2 weeks because of tumor lysis syndrome (Figure). After 2 cycles of treatment, the patient achieved a CR. By week 3, platelets and neutrophils recovered, indicating a specificity of forodesine for leukemic cell populations. These study results show that forodesine is active, with minimal toxicity, as a single agent in relapsed or refractory T-cell leukemia. Additional clinical efficacy and safety data will be presented. Effect of Forodesine on Blood Components in One T-All Patient Effect of Forodesine on Blood Components in One T-All Patient

Description: Activating mutations in the receptor tyrosine kinase FLT3 are present in approximately 30% of patients (pts) with acute myeloid leukemia (AML), and they have a significantly worse prognosis than pts with wild type (WT) FLT3, suggesting that the activated kinase is a driver of the disease and a potential target for kinase inhibitor therapy. AC220 is a novel 2nd generation class III receptor tyrosine kinase (RTK) inhibitor with potent in vitro and in vivo activity in FLT3-dependent tumors. It is highly selective for WT and mutant FLT3 and several other class III RTKs, including KIT, CSF1R, RET and PDGFR. AC220 is in a first-in-human phase 1 study for relapsed or refractory AML pts, unselected for FLT3 mutations. The study has a standard 3+3 dose escalation design with 50% dose increments. AC220 is administered once daily as an oral solution for 14 days followed by a 14 day rest period (1 cycle) with a starting dose of 12 mg. Concurrently, pts are being dosed on a continuous dosing regimen starting at 200 mg/day for 28 days (1 cycle). Pts with clinical benefit may continue to receive further cycles. Currently, 52 pts have been dosed with AC220 up to 450 mg/day (10 dose cohorts). Median age was 60 yrs (range, 23 to 86 yrs), median number of prior therapies was 3 (range, 0 to 8) and 2 pts had prior allogeneic hematopoietic stem cell transplant (HSCT). Two elderly patients (age ≥ 78 yrs) unfit for induction chemotherapy were previously untreated. Fifteen patients have FLT3 mutations (12 ITD and 3 TKD), 25 are WT, and 12 are undetermined. Pts are also evaluated for PK, pFLT3, pSTAT5, FLT3 genotyping and ex vivo plasma inhibitory activity. AC220 is well tolerated and MTD has not yet been observed with either schedule. One pt had a possibly drug-related DLT in the 18 mg cohort (grade 3 CHF, although pt had a pre-existing heart condition) leading to cohort expansion, but no other cases of drug-related CHF or other DLT have been seen. Other possibly drug-related AEs (most frequently gastrointestinal events) were mild (grade ≤ 2). Response data based on investigator’s assessment are available on the first 45 pts. Responses were observed in 11 (24%) pts. Four pts achieved a complete response (CR) – 2 with incomplete platelet recovery (CRp) and 2 with incomplete platelet and neutrophil recovery (CRi), one of these pts also had complete resolution of leukemia cutis. In addition, 7 pts had partial responses (PR, defined as a decrease of ≥ 50% blasts to levels of 5%–25% in the bone marrow). Most responses (8/11, 73%) occurred after cycle 1 and one was observed after cycle 3. Median duration of response is 18 weeks (range, 4 to 26+ weeks). Three responders are FLT3 mutants (2 ITD and 1TKD), 5 are WT, 3 are undetermined. Six of the 9 non-responding pts with ITD mutations had initial rapid clearing of peripheral blasts with intermittent AC220 dosing, but subsequently progressed or had disease-related mortality. All these pts had aggressive disease and received a median of 6 prior treatment regimens (range, 3 to 8). AC220 plasma exposure is sustained between dose intervals and continues to increase in a dose-proportional manner from 12 mg to 300 mg. FLT3 phosphorylation is strongly suppressed when plasma obtained from study pts is tested ex vivo in FLT3-ITD and WT cell lines at 12 mg and 60 mg doses, respectively. Assessments of pFLT3 and pSTAT5 from treated pts’ peripheral blood are ongoing and will be presented. Encouraging preliminary efficacy results and an acceptable safety profile warrants continued evaluation of AC220 as a single agent and in combination with other therapeutics for the treatment of AML.

Description: Abstract 1507 FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are associated with early relapse after standard chemotherapy and poor survival. Quizartinib is an oral FLT3 receptor tyrosine kinase (RTK) inhibitor that inhibits both ITD-mutant and wild-type FLT3 and displays efficacy in preclinical models of AML. In this first-in-human study, quizartinib was evaluated in patients with relapsed or refractory AML who were enrolled irrespective of FLT3-ITD status. Quizartinib was administered orally on an intermittent schedule (ID, 14 days on, 14 days off) at 12–450 mg/day or continuously (CD) at 200 or 300 mg/day. A total of 76 patients (61% male; 90% white; median age 60 years [23–86]) received quizartinib; median number of prior treatments was 3 (0–12), including 16% with a prior hematopoietic stem cell transplant. FLT3-ITD status was 22% positive (+) (n=17), 49% negative (−) (n=37), and 29% indeterminate/not tested (ind) (n=22). Plasma inhibitory activity assays using plasma samples collected at trough timepoints showed a high degree of FLT3 inhibition at low dose levels (18 mg/day and higher), indicative of potent in vivo FLT3 inhibition. Marked inhibition of FLT3 phosphorylation was also demonstrated in peripheral blood following administration of quizartinib. Responses were observed in 23/76 patients (30%), with 10 patients (13%) having a best response of any type of complete remission (CR=morphologic leukemia-free state with absolute neutrophil count 〉1×109/L and platelet count ≥100×109/L, and normal marrow differential with

Description: Abstract 636 Activating mutations in the FLT3 RTK are present in ∼30% of AML patients (pts), who have a significantly worse prognosis than pts with wild type (WT) FLT3. AC220 is a novel 2nd generation RTK inhibitor with potent in vitro and in vivo activity in FLT3- and KIT-dependent tumor cell lines. It is highly selective for both WT and mutant FLT3 with significant activity against KIT. A first-in-human Phase 1 study investigating AC220 in predominantly relapsed or refractory AML pts, unselected for FLT3 mutations, was recently completed, using a standard 3+3 dose escalation with 50% dose increments. AC220 was administered once daily as an oral solution initially with an intermittent dosing (ID) regimen: 14 days on and 14 days off (1 cycle). Starting dose was escalated from 12 to 450 mg/day ID. Additional cohorts were investigated on a continuous dosing (CD) regimen: 200 and 300 mg/day for 28 days (1 cycle). A total of 76 pts (46 male, 30 female) were dosed with AC220. Median age was 60 yrs (23-86), median number of prior therapies was 4 (0-9), 12 pts had prior allogeneic transplant and 3 elderly pts (≥72 yrs) unfit for induction chemotherapy were previously untreated. Eighteen pts (24%) had FLT3 ITD mutations, 47 (62%) were WT, and 11 (14%) were undetermined. Pts were also evaluated for PK, phosphorylated (p) FLT3, pKIT, pSTAT5, and ex vivo plasma inhibitory activity. AC220 plasma exposure was sustained between dose intervals and continued to increase in a dose-proportional manner from 12 to 450 mg with a half-life of ∼1.5 days. An active metabolite, AC886, was detected that has similar potency and activity to AC220. Patient plasma at '12 mg potently inhibited pFLT3 in ex vivo FLT3-ITD cell lines and complete inhibition of pFLT3 in WT cell lines was observed at higher doses. Target inhibition was also observed, with suppression of pFLT3, pSTAT5 and pKIT in peripheral blasts. The most commonly reported possibly drug-related AEs were GI events, peripheral edema, and dysguesia, which were Grade ≤2. DLT was observed at 300 mg CD and 200 mg CD was declared as the MTD. Two pts at 300 mg CD had possibly study drug-related DLTs with grade 3 QTc prolongation, but had confounding factors including concomitant medications known to prolong QTc. Responses (IWG criteria) were observed in 23 (30%) pts. PR and CR were observed as low as the 18 and 40 mg cohorts, respectively. Most responses occurred within cycle 1. Overall, 9 (12%) pts had a complete response (CR) with 2 CR, 5 CRi, and 2 CRp. One of these pts also had complete resolution of leukemia cutis. In addition, 14 (18%) pts achieved PR. Overall median duration of response (MDOR) was 14 (4-62+) weeks and overall median survival (MS) was 14 (1-68+) weeks. In FLT3-ITD pts the MDOR was 12 (4-27+) weeks and the MS was 18 (3-42) weeks. In FLT3-WT pts the MDOR was 32 (8-62+) weeks and the MS was 11 (1-68+) weeks. 10 (56%) of 18 FLT3-ITD pts were responders (1 CR, 3 CRi, 6 PR), 9 (19%) of 47 FLT3-WT pts (1 CRi, 2 CRp, 6 PR), and 4 (36%) of 11 undetermined pts (1 CR, 1 CRi, 2 PR). At 200 mg CD (MTD expansion), 4 of 6 FLT3-ITD pts responded (1 CR, 1 CRp, 1 CRi, 1 PR). Of the 4 responders, 2 failed prior treatment with sorafenib and 2 previously refractory pts went onto transplant. The 2 FLT3-ITD non-responders had 6 and 8 prior lines of therapy, respectively. These encouraging efficacy results and an acceptable safety profile warrant continued evaluation of AC220 as monotherapy and in combination therapy for the treatment of AML. Phase 2 studies in FLT3-ITD positive and WT pts are in progress. Disclosures: Cortes: Ambit Biosciences: Research Funding. Foran:Ambit Biosciences: Research Funding. Ghirdaladze:Ambit Biosciences: Research Funding. DeVetten:Ambit Biosciences: Research Funding. Zodelava:Ambit Biosciences: Research Funding. Holman:Ambit Biosciences: Research Funding. Levis:Ambit Biosciences: Consultancy, Research Funding. James:Ambit Biosciences: Employment. Zarringkar:Ambit Biosciences: Employment. Gunawardane:Ambit Biosciences: Employment. Armstrong:Ambit Biosciences: Employment. Padre:Ambit Biosciences: Employment. Wierenga:Ambit Biosciences: Employment. Corringham:Ambit Biosciences: Employment. Trikha:Ambit Biosciences: Employment.

Description: Background: CT-P10 is a biosimilar candidate to the reference rituximab product, EU-approved MabThera® and US-licensed Rituxan®. CT-P10 has an identical amino acid sequence and highly similar physicochemical and in vitro functional properties to its reference drug. In patients with rheumatoid arthritis, CT-P10 has demonstrated compelling similarity in pharmacokinetics (PK), pharmacodynamics (PD), efficacy, safety and immunogenicity (Yoo DH, et al. Arthritis Rheum. 2013;65(10):1736). Objective: The goal of this study was to demonstrate PK similarity of CT-P10 to rituximab, each administered in combination with cyclophosphamide, vincristine, and prednisone (CVP) in patients with newly diagnosed Advanced Follicular Lymphoma (AFL) (NCT02162771) (Kim WS et al. Blood. 2015;126(23): 5111). The results of PK, PD, safety and immunogenicity up to Core Cycle 4 (12 weeks) are presented here from this ongoing study. Methods: Patients with AFL were randomized 1:1 to receive infusion (375mg/m2) of either CT-P10 or rituximab, at a 3-week interval, in combination with CVP. PK analysis was conducted in terms of AUCtau and Cmax at steady state, Core Cycle 4, as primary PK endpoints. PK parameter values considered as outliers determined by robust regression outlier testing were excluded from the pharmacokinetic primary analysis. Results: In total, 121 patients were randomly assigned to receive either CT-P10 (n=59) or rituximab (n=62) in combination with CVP. Result of CT-P10 PK at Core Cycle 4 was similar to that of rituximab. The ratios (90% CI) of geometric least square means (CT-P10 to rituximab treatment group) were 102.3% (94.1%-111.2%) for AUCtau and 100.7% (93.8%-108.0%) for CmaxSS at Core Cycle 4. The 90% CIs of ratio of geometric LS means for both AUCtau and CmaxSS were entirely contained within the equivalence margin of 80% to 125% (Table 1 and Figure 1). Mean serum concentrations of the study drug were highly similar for the 2 treatment groups at each time point (Core Cycle 1 to 4). The B-cell kinetics was similar up to Core Cycle 4 in the 2 treatment groups. Median number of B-cells decreased to below the lower limit of quantification (LLoQ) (20 cells/μL) 1 hour after the end of infusion at Core Cycle 1 and remained below the LLoQ at each subsequent cycle, up to and including Core Cycle 4. The proportion of patients with a positive anti-drug antibody up to Core Cycle 4 at post-treatment visits was similar between the 2 treatment groups; 3/59 (5.1%) patients and 2/62 (3.2%) patients in the CT-P10 and rituximab groups, respectively. In addition, CT-P10 was well tolerated and the safety profile of CT-P10 up to Core Cycle 4 was similar to that of rituximab. The number of patients who experienced at least 1 treatment emergent adverse event (TEAE) was 43 (72.9%) patients and 41 (66.1%) patients in CT-P10 and rituximab treatment groups, respectively. The proportion of patients who experienced at least 1 treatment emergent serious adverse event considered by the investigator to be related to the study treatment was similar between the 2 treatment groups; 2/59 (3.4%) patients and 2/62 (3.2%) patients in the CT-P10 and rituximab groups, respectively. The frequencies of adverse events special interest (AESI) were similar between the 2 treatment groups (Table 2). Conclusion: This study demonstrated similarity of PK in terms of AUCtau and CmaxSS between CT-P10 and rituximab in AFL patients. The B-cell kinetics and immunogenicity were comparable between the two treatment groups. CT-P10 was well tolerated with a safety profile comparable to that of rituximab up to and including Core Cycle 4 (12 weeks). Table 1 Statistical Analysis of Rituximab Pharmacokinetic Primary Endpoints for Core Cycle 4 at Steady State: Pharmacokinetic Population Table 1. Statistical Analysis of Rituximab Pharmacokinetic Primary Endpoints for Core Cycle 4 at Steady State: Pharmacokinetic Population Figure 1 Mean (±SD) Serum Concentration of Rituximab Versus Time for Cycle 4 at Steady State (Linear Scale): Pharmacokinetic Population Figure 1. Mean (±SD) Serum Concentration of Rituximab Versus Time for Cycle 4 at Steady State (Linear Scale): Pharmacokinetic Population Table 2 The Incidence Rates of Adverse Events Special Interest: Safety Population Table 2. The Incidence Rates of Adverse Events Special Interest: Safety Population Disclosures Coiffier: Celltrion, Inc.: Consultancy, Honoraria. Sancho:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jurczak:Celltrion, Inc: Research Funding; Gilead Sciences: Research Funding; Acerta: Research Funding; Bayer: Research Funding; Janssen: Research Funding. Kim:Celltrion, Inc.: Research Funding. Nagarkar:Celltrion, Inc.: Research Funding. Zhavrid:Celltrion, Inc.: Research Funding. Hernandez Rivas:Celltrion, Inc.: Research Funding. Prokharau:Celltrion, Inc.: Research Funding. Zodelava:Celltrion, Inc.: Research Funding. Osmanov:Celltrion, Inc.: Research Funding. Ogura:SymBio Pharmaceuticals: Consultancy, Honoraria; Celltrion, Inc.: Consultancy, Honoraria. Buske:Celltrion, Inc.: Consultancy, Honoraria. Kwak:Celltrion, Inc.: Consultancy. Kim:Celltrion, Inc.: Consultancy, Honoraria.

Description: Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin Lymphoma (NHL) accounting for approximately 30-40% of NHL cases. Approximately 40% of all newly diagnosed DLBCL patients are either refractory or relapsed following initial response to therapy and represent a population with high unmet need for new therapeutic strategies to achieve or regain disease remission. Because of the near ubiquity and persistence of CD20 expression in B-cell malignancies, there is strong rationale to develop compounds with novel mechanisms of action targeting CD20. However, CD20's non-internalizing nature has, to date, leveraged only cytotoxic mechanisms such as antibody-dependent cellular cytotoxicity to which resistance can arise and has impeded the development of agents that internalize a cytotoxic payload. MT-3724 is a novel engineered toxin body designed to overcome this limitation by combining the specific target selectivity of a single chain variable fragment with the lethality of a genetically fused Shiga-like toxin A subunit that facilitates both internalization and cell killing by inactivating ribosomal protein synthesis. MT-3724 has been shown to specifically bind and kill CD20+ malignant human B-cells in vitro (IC50

Description: Background: The near ubiquity and persistence of CD20 expression in B-cell malignancies provides a strong rationale for novel CD20-directed therapies. MT-3724 is a novel engineered toxin body comprised of an anti-CD20 single chain variable fragment genetically fused to Shiga-like toxin A subunit, which forces internalization of CD20-bound MT-3724, irreversibly inactivating ribosomes and triggering apoptosis. As MT-3724 competes with rituximab (RTX) for the same CD20 binding domain, undetectable or low (〈 500 ng/mL) RTX levels (RTX-neg) allow potential response to MT-3724. We present final safety and efficacy results from dose escalation to maximum tolerated dose (MTD) in Non-Hodgkin Lymphoma (NHL) subjects (subj) and dose expansion in RTX-neg DLBCL subj. Methods: In Part 1, MT-3724 dose was escalated in 21 subj with B-cell NHL according to the 3+3 design based on ≤1 subj exhibiting DLT during Cycle 1 (28 days) in 6 sequential dose cohorts (5, 10, 20, 50, 75, and 100 μg/kg/dose IV over 2 hours 3 times per week for 2 of 4 consecutive weeks) for up to 5 cycles. In Part 2, the safety and efficacy of MT-3724 was further evaluated in 6 RTX-neg subj with DLBCL. Tumor response was assessed by the International Working Group Response Criteria for Clinical Trials (Cheson 2007). Results: Twenty-seven subj with NHL (DLBCL:16, composite DLBCL/Follicular Lymphoma (FL): 3, FL: 6, Mantle Cell Lymphoma: 2 were enrolled. Seventeen (63%) were female, mean age was 65 yrs (34-78). Performance status was ECOG 0: 44%, 1: 44%, 2: 11%; median follow-up was 50 (11-372) days; median cycles 2 (1-11). The most common AEs (%) of all grades were peripheral edema (63), fatigue (41), diarrhea (41), myalgia (41), muscle weakness (33), insomnia (30); 27 subj had AEs (%) with related causality, the most common were: peripheral edema (41), myalgia (33), fatigue (26). The most common related grade (G) ³3 AEs included neutropenia, myalgia, and infections (all 11%); There were 9 related SAEs among 6 subj. One subj died on study from disease progression. MT-3724 was not tolerated at 100 µg/kg/dose (DLTs: G3 pneumonia, G2 ileus). After 2 obese (BMI 〉35) subj treated at 75 µg/kg/dose in the expansion cohort had G2 capillary leak syndrome (CLS), the MTD was set at 50 µg/kg/dose with a 6000 mg/dose cap. Innate immune responses such as CLS or manifestations thereof (hypotension, hypoalbuminemia, peripheral edema) were noted with increasing frequency with higher doses of MT-3724. No cases of 〉G2 CLS have been observed. Of the 13 RTX-neg DLBCL subj, 5 (38%) responded across the range of 5 to 50 μg/kg/dose. All responses were partial responses (PRs) including 1 subj with composite DLBCL/FL post autologous stem cell transplantation (SCT) who had a complete metabolic response of a large mesenteric mass and proceeded to allogeneic SCT. Three subj had stable disease (SD) including two with 49% and 47% tumor reductions, one of whom had FL transformed from DLBCL post autologous SCT; another 5 had progressive disease. Given a limited prescribed period of treatment with MT-3724, duration of response cannot be calculated, however, generally the tumor burden in responders decreased with repeat treatment. Among the responders, mean age was 61 (50-76) yrs, and the median number of prior lines of NHL therapy received was 3 (1-8). Subj with detectable baseline RTX levels did not benefit from MT-3724. Of all 20 subj measured, 6 developed anti-drug antibodies (ADAs) during the first cycle of therapy; 5 developed ADAs at a later timepoint; 6 did not develop ADAs. ADAs were observed in all subj who showed a response, and in 4 of 5 subj with SD. Increasing MT-3724 dose was associated with a dose-dependent peripheral B-cell depletion, evidenced by decreasing CD19+ cells. Conclusions MT-3724 is the first CD20 targeted immunotoxin to enter clinical trials. Safety events were mostly mild-moderate, and DLTs were in line with the mechanism of action of MT-3724. A tolerable dose and schedule have been identified: 50 μg/kg/dose up to a maximum of 6000 μg/dose infused over 1 hour on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. A 38% objective response rate has been observed with monotherapy in a heavily pretreated, RTX-neg DLBCL population; of these subj, 5 were treated at 50 ug/kg (MTD) and 3 of whom responded. The development of ADAs did not preclude benefit of MT-3724. An ongoing phase 2 monotherapy study to confirm efficacy and safety in RTX-neg subj with DLBCL (NCT02361346) is open for recruitment. Disclosures Musteata: Institute of Oncology: Employment; Arensia EM: Other: Principal Investigator. Park:BMS: Consultancy, Research Funding; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Burnett:Molecular Templates, Inc.: Employment. Dabovic:Molecular Templates, Inc.: Employment. Williams:Molecular Templates, Inc.: Employment. Higgins:Molecular Templates, Inc.: Employment, Equity Ownership. Persky:Sandoz: Consultancy; Morphosys: Other: Member, Independent Data Monitoring Committee; Debiopharm: Other: Member, Independent Data Monitoring Committee; Bayer: Consultancy.

Description: Introduction: Despite high response rates to initial treatment, relapse is common in CLL. Although newer agents are approved for treatment recently, CLL remains an incurable disease. Tenalisib (RP6530) is a highly specific and orally available PI3K δ/γ+SIK3 inhibitor. In in-vitro studies, Tenalisib was highly effective (62nM) in demonstrating a cytotoxic effect in patient derived CLL cells and showed very good synergism in combination with fludarabine and ibrutinib at very low concentrations in patient derived primary CLL cells. Tenalisib has demonstrated good clinical activity in patients with T cell lymphomas. Previously, a pooled safety analysis of 93 patients treated with tenalisib monotherapy demonstrated a differentiated safety profile which is largely devoid of immune mediated toxicities (Iyer, ASH 2018). Methods: This trial is a Phase II, open label, multi-center, Simon's two stage study design to evaluate the efficacy and safety of Tenalisib in patients with CLL who have relapsed or are refractory after at least one prior therapy. In stage 1, 20 patients were to be enrolled and an additional 41 patients to be enrolled in stage 2 based efficacy results of stage 1 (〉8 responders needed to proceed to stage 2). Patients with previously treated CLL with adequate bone marrow, liver, and renal function, ECOG ≤2, and measurable disease are eligible. Patients with prior exposure to drug that specifically inhibits PI3K were excluded. The primary objective was to assess the anti-tumor activity. The secondary objectives were to assess safety and tolerability, and progression free survival (PFS). The responses were assessed using iwCLL criteria (Hallek 2018). Results: A total of 21 CLL patients predominantly male (86%) with median age was 66 years (range 44-79) were enrolled between Dec 2019 and March 2020 in Stage 1 of the study. 67% of patients had an ECOG score of 1, and 43% had Rai Stage III/IV disease with 67% having spleno/hepatomegaly. Patients had a median of 2 (range: 1-3) prior treatment regimens and 16 (76%) were refractory to last therapy. High risk patients included 15% del 17p, 10% del 11q, 5% ZAP and 5% TP53 mutations. In all 21 evaluable pts with a median follow-up of 4.9 months, 7 patients showed partial response (33%) while the remaining 14 patients showed stable disease (67%). 19 patients (90%) were still continuing therapy while 2 patients discontinued due to disease progression after showing a stable response. There was a median reduction in nodal disease to the extent of 54% in responding patients. The data readouts at C8D1 for all patients is currently awaited. The most common AEs which were mild-moderate in severity included transaminitis (19%), GGT elevation (5%) and neutropenia (5%). There was a related Grade 3 AE of neutropenia (5%). None of the related AEs led to study discontinuation. There were no events of diarrhoea/colitis or pneumonitis in patients who were on therapy for more than 6 months. Conclusions: Tenalisib showed promising single agent anti-tumor activity in patients with CLL with a favourable safety profile. Further data is awaited to estimate the response rates and the decision to move to Stage 2 of the study. Disclosures Robak: Momenta: Consultancy; BioGene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Takeda: Consultancy; Pfizer: Research Funding; UCB: Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; UTX-TGR: Research Funding; Acerta: Research Funding; Morphosys: Research Funding; AstraZeneca: Honoraria, Research Funding; Bristol Meyers Squibb: Research Funding; Sandoz: Consultancy, Honoraria; Octapharma: Honoraria; Medical University of Lodz: Current Employment; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; GSK: Research Funding; Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding. Routhu:Rhizen Pharmaceuticals S.A〉.: Current Employment. Barde:Rhizen Pharmaceuticals S.A: Current Employment. Nair:Rhizen Pharmaceuticals S.A.: Current Employment.