A PHASE 1/1B DOSE-ESCALATION TRIAL EVALUATING CPI-818, AN ORAL INTERLEUKIN-2-INDUCIBLE T-CELL KINASE INHIBITOR, IN PATIENTS WITH RELAPSED/REFRACTORY T-CELL LYMPHOMA

Abstract Background: The prognosis of patients with PTCL remains poor after standard CHOP therapy - the most commonly used combination regimen. Relapses occur in the majority of patients, and curability rates of the relapsed disease are very low. Hence, advances in front-line therapy of PTCL are long overdue. Pralatrexate, a second-generation antifolate, demonstrated a single agent activity in patients with relapsed and refractory PTCL with a response rate of 27%, including complete remissions in 11% of patients (O'Connor et al. J Clin Onc 2011). We conducted a Phase 1 multi-center dose-escalation study of pralatrexate in combination with standard CHOP (Fol-CHOP) in treatment-naïve PTCL patients. Objectives: The primary objective of the study was to determine the maximum tolerated dose (MTD) of pralatrexate when administered with a standard CHOP regimen to patients with newly diagnosed PTCL. The secondary objectives included safety, tolerability, efficacy and pharmacokinetics of pralatrexate in combination with CHOP (Fol-CHOP). Methods: In Part 1 of this 3+3 dose-escalation study, pralatrexate was administered at 10, 15, 20, 25, or 30 mg/m2 as an IV push on days 1 and 8 of a standard 21-day CHOP regimen (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 [maximum 2 mg] on day 1 and oral prednisone 100 mg on days 1-5). In Part 2 of the study patients were treated at the MTD of pralatrexate established in Part 1, with standard CHOP. In both parts of the study patients were treated with up to 6 cycles of therapy, or until toxicity or disease progression. Patients received antimicrobial prophylaxis, myeloid growth factor support, and "leucovorin rescue" throughout 6 cycles of therapy. Dose-limiting toxicities (DLT) were considered during the 1st cycle of Fol-CHOP and included: Grade 4 infections, treatment-related non-hematological toxicity ≥Grade 3, platelet count < 25 X 109/L at any time, or ANC < 0.5 X 109/L for >7 days despite G-CSF administration. Responses were assessed by the investigator per the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Results: A total of 31 patients have been enrolled (19 in Part 1; 12 in Part 2). MTD was not reached and pralatrexate dose of 30 mg/m2 in combination with CHOP was selected for Part 2 of the study as predefined by the protocol. The majority of patients were male, White, with the median age of 66 yrs (range, 18-78) at the time of enrolment. PTCL diagnoses included: anaplastic large cell lymphoma, anaplastic lymphomakinase-negative (ALCL, ALK-, n=5), peripheral T-cell lymphoma, not-otherwise specified (PTCL-NOS, n=18), and angioimmunoblastic T-cell lymphoma (AITL, n=5). Fol-CHOP was generally well tolerated with median RDI of 98%. Common (≥ 30%) adverse events (AEs) of any grade were fatigue (n=23), constipation (n=20), nausea (n=16), mucositis (n=14), diarrhea (n=12), anemia (n=9), vomiting (n=10) and oral pain (n=10). Most common (≥ 10%) AEs ≥ grade 3 were anemia (n=6), fatigue (n=4) and neutrophil count decreas (n=5). The only Grade >3 treatment-related AEs (≥10%) was neutrophil count decrease (n=4). SAEs were observed in 13 patients, treatment related SAEs were anemia, febrile neutropenia, dehydration, mucositis and nausea. Five patients withdrew from study: 2 due to disease progression, 1 due to AE and 2 due lapse >28 days between doses. In the 27 patients avaluable for response, the investigator assessed objective response (OR) and complete response (CR) rates were 89% wand 67%, respectively. Conclusions: The combination of pralatrexate and CHOP was well tolerated in treatment-naive PTCL patients. MTD of pralatrexate was not reached, and the protocol-defined maximum dose of 30 mg/m2 on days 1 and 8 of a 21-day CHOP cycle was recomended for future studies. The observed OR and CR rates warrant further evaluation of this regimen in newly diagnosed PTCL patients. Disclosures Shustov: Celgene: Other: Publication assistance; Spectrum Pharmaceuticals: Consultancy, Research Funding. Bhat: Spectrum Pharmaceuticals: Employment. Reddy: Spectrum Pharmaceuticals: Employment.

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Phase I Dose-Escalation Study of Cpi-613, in Combination with Bendamustine, in Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma

Blood ◽

10.1182/blood.v128.22.4163.4163 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4163-4163 ◽

Cited By ~ 4

Author(s):

Zanetta S. Lamar ◽

Scott Isom ◽

Rakhee Vaidya ◽

Anne W Beaven ◽

Zachariah A. McIver

Keyword(s):

T Cell ◽

Dose Escalation ◽

Response Rate ◽

Cell Lymphoma ◽

Phase 1 ◽

Single Agent ◽

Hematologic Malignancies ◽

T Cell Lymphoma ◽

Non Hodgkin Lymphoma ◽

Grade 3

Abstract Background:T cell lymphomas account for 10-15% of lymphoid malignancies and display significant heterogeneity. T cell lymphomas have a worse prognosis than most B cell lymphomas. For relapsed or refractory disease, there is not a standard treatment and median progression free and overall survival rates have been reported as 3.7 and 6.5 months, respectively. Therefore, optimal treatment for relapsed/refractory T cell Non-Hodgkin Lymphoma (NHL) is an unmet clinical need. CPI-613 is a lipoate derivative that has shown activity in hematologic malignancies. CPI-613 selectively targets the pyruvate dehydrogenase complex (PDC) and α-ketoglutarate dehydrogenase complex (KGDHC) in tumor cells. CPI-613 leads to the inhibition of the catalytic and regulatory functions of the PDC and the KGDHC causing alterations of mitochondrial enzyme complex activities and altering redox status, leading to apoptosis, necrosis and autophagy of tumor cells. The anti-tumor activity of CPI-613 is evident in various cancer cell lines, xenograft animal tumor models and clinical trials against a diverse group of cancers. Patients tolerate CPI-613 as a single agent at doses up to 3,000 mg/m2, according to Phase 1 trials in patients with solid tumors and hematologic malignancies. Bendamustine has shown single agent activity in the relapsed lymphoma setting with response rates of approximately 50% for T cell NHL. Here, we are conducting a Phase I study in which the primary objective was to evaluate the maximum tolerated dose (MTD) of CPI-613 while administered in combination with Bendamustine. The secondary objective was to determine response rate to treatment. Methods: This study is a phase 1, open label, modified 3+3 dose escalation clinical trial evaluating CPI-613 and Bendamustine combination therapy. CPI-613 was given at escalating doses starting at 2,000mg/m2 over 2 hrs on days 1-4, and on days 8, 11, 15 and 18. Bendamustine was infused at 90 mg/m2 on days 4 and 5 of each treatment cycle. Each treatment cycle was 4 weeks and repeated up to six cycles. Demographics, patient characteristics and dose levels are shown in the table below. There was no intra-patient dose escalation. Results: As of July 27, 2016, eight subjects have received at least one dose of study drug. Eight patients are evaluable for safety and five patients are evaluable for response. The most common grade 3 or higher toxicities were lymphopenia and neutropenia and occurred in 4 subjects. One patient dosed at 2750 mg/m2 had a dose limiting toxicity of grade 3 acute kidney injury and grade 4 lactic acidosis. The protocol was later amended to discontinue dose escalation at doses of 2750 mg/m2 or higher and to expand the 2500mg/m2 cohort. The overall response rate was 80%. Three patients with peripheral T cell lymphoma, NOS, obtained a complete response and 1 patient with mycosis fungoides had a partial response. One patient with T cell acute lymphomoblastic lymphoma had progressive disease. The median time to response is 1.8 months. Enrollment is ongoing and updated trial results will be presented. Conclusions: This first reported study of CPI-613 administration in combination with Bendamustine in subjects with relapsed or refractory T cell lymphoma showed a good safety profile and an excellent overall response rate of 80% with CRs in all three patients with peripheral T cell lymphoma, NOS. Although numbers are small, continued investigation is warranted as these response rates in a poor risk population of patients with relapsed/refractory T cell lymphoma are very exciting. Clinical trial: NCT02168907 Disclosures No relevant conflicts of interest to declare.

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Toxicity and efficacy of alemtuzumab combined with CHOP for aggressive T-cell lymphoma: a phase 1 dose-escalation trial

Leukemia & Lymphoma ◽

10.1080/10428194.2019.1576870 ◽

2019 ◽

Vol 60 (9) ◽

pp. 2291-2294 ◽

Cited By ~ 1

Author(s):

Elizabeth H. Phillips ◽

Stephen Devereux ◽

John Radford ◽

Naheed Mir ◽

Toyin Adedayo ◽

...

Keyword(s):

T Cell ◽

Dose Escalation ◽

Cell Lymphoma ◽

Phase 1 ◽

T Cell Lymphoma

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A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma

Blood ◽

10.1182/blood-2004-11-4570 ◽

2005 ◽

Vol 106 (2) ◽

pp. 454-457 ◽

Cited By ~ 79

Author(s):

Francine Foss ◽

Marie France Demierre ◽

Gina DiVenuti

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Phase 1 ◽

Interleukin 2 ◽

T Cell Lymphoma ◽

Leukemia Cells ◽

Cutaneous T Cell Lymphoma ◽

Phase 1 Trial ◽

Denileukin Diftitox

Abstract Denileukin diftitox, a genetically engineered fusion protein combining the enzymatically active domains of diphtheria toxin and the full-length sequence for interleukin-2 (IL-2), efficiently targets lymphoma cells expressing the high-affinity IL-2 receptor (IL-2R) consisting of the α/p55/CD25, β/p75/CD122, and γ/p64/CD132 chains. In vitro studies demonstrated that the retinoid X receptor (RXR) retinoid, bexarotene, at biologically relevant concentrations of 10–6M to 10–8 M, upregulated both the p55 and p75 subunits of the IL-2R and enhanced 5- to 10-fold the susceptibility of T-cell leukemia cells to denileukin diftitox. To determine whether this biomodulatory effect could be recapitulated in vivo, we treated 14 patients with relapsed or refractory cutaneous T-cell lymphoma with escalating doses of bexarotene (75 mg/day-300 mg/day) and denileukin diftitox (18 mcg/kg per day × 3 days every 21 days) in a phase 1 trial. Overall response was 67% (4 complete responses, 4 partial responses). Modulation of IL-2R expression was observed at or above a bexarotene dose of 150 mg/day. Four patients experienced grade 2 or 3 leukopenia, and 2 had grade 4 lymphopenia. Our results demonstrate that the combination of denileukin diftitox and bexarotene is well tolerated and that even low doses (150 mg/day) of bexarotene are capable of in vivo upregulation of CD25 expression on circulating leukemia cells.

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Lenalidomide in relapsed adult T-cell leukaemia-lymphoma or peripheral T-cell lymphoma (ATLL-001): a phase 1, multicentre, dose-escalation study

The Lancet Haematology ◽

10.1016/s2352-3026(15)00284-7 ◽

2016 ◽

Vol 3 (3) ◽

pp. e107-e118 ◽

Cited By ~ 28

Author(s):

Michinori Ogura ◽

Yoshitaka Imaizumi ◽

Naokuni Uike ◽

Norio Asou ◽

Atae Utsunomiya ◽

...

Keyword(s):

T Cell ◽

Dose Escalation ◽

Cell Lymphoma ◽

Phase 1 ◽

T Cell Lymphoma ◽

Cell Leukaemia ◽

Peripheral T Cell Lymphoma ◽

Dose Escalation Study

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A Dose Escalation Study of RP6530, a Novel Dual PI3K δ/γ Inhibitor, in Patients with Relapsed/Refractory T-Cell Lymphoma

Blood ◽

10.1182/blood.v128.22.3004.3004 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3004-3004 ◽

Cited By ~ 2

Author(s):

Yasuhiro Oki ◽

Auris Huen ◽

Prajak J Barde ◽

Kumar Penmetsa ◽

Alda Ashu ◽

...

Keyword(s):

T Cell ◽

Adverse Events ◽

Dose Escalation ◽

Cell Lymphoma ◽

Phase 1 ◽

Performance Status ◽

T Cell Lymphoma ◽

Clinical Activity ◽

Dose Escalation Study ◽

Grade 3

Abstract Introduction: The δ isoform of PI3K is highly expressed in cells of hematopoietic origin. The γ isoform is associated with T-lymphocytes and neutrophils and plays a distinct role in T-cell function. Since δ/γ isoforms are synergistic in the growth and survival of certain T-cell malignancies, dual targeting of PI3K δ/γ is an attractive intervention strategy in patients with T-cell lymphoma. RP6530 is a novel, highly specific dual PI3K δ/γ inhibitor with nanomolar inhibitory potency for both isotypes. It has shown acceptable safety profile and efficacy in patients (pts) with advanced hematologic malignancies in a Phase 1 study (ASH 2015). Herein, we present the preliminary results from an ongoing Phase 1/1b, dose escalation study of RP6530 in 11 pts with mature T-cell neoplasms (NCT02567656). Methods: The study consists of dose escalation cohorts to determine the MTD of RP6530 using a standard 3+3 design, followed by two expansion cohorts enrolling 20 pts with peripheral T-cell lymphoma (PTCL) and 20 pts with cutaneous T-cell lymphoma (CTCL). Pts with a diagnosis of PTCL or CTCL who have received at least one prior systemic therapy, ECOG performance status ≤ 2 and measurable/evaluable disease are eligible. This study evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and clinical activity of RP6530 administered twice daily (BID) in 28-day cycles. Responses were evaluated for PTCL and CTCL based on IWG criteria (Cheson 2014) and the modified Severity Weighted Assessment Tool (mSWAT) respectively. Dose limiting toxicity (DLT) was defined by a toxicity of grade 3/4 that is considered related to treatment during the first cycle of treatment. Results: To date eleven pts (6 PTCL and 5 CTCL) (5 males and six females) have been enrolled at three dose levels: 200 mg BID, 400 mg BID and 800 mg BID. ECOG performance status score was 0/1/2 in 10/1/0 pts, respectively, with a mean age of 68 yrs (range 52-76). Pts had a median of 3 (range: 3-6) prior treatment regimens, and 5 pts had refractory disease and 6 relapsed on prior treatments. RP6530 was well tolerated without any DLT or related serious adverse event reported to date. A total of 52 non-serious adverse events were reported: 41 Grade 1/2 and 11 Grade 3/4. The most common adverse events included mild vomiting (18%), diarrhoea (18%), fatigue (18%), and rash (18%). No Grade 3/4 adverse events were deemed related to RP6530 except for ALT/AST elevation in one pt. No pt discontinued treatment due to a safety issue. Dose-proportional increases in plasma concentrations were observed in PKs. Dose escalation is currently ongoing at 800 mg BID. Five pts were evaluated for responses at Cycle 3, Day1. Two pts (1 PTCL and 1 CTCL) experienced PR (40%) that are ongoing >5 months, and three pts experienced stable disease lasting for >3 months (60%). Three pts experienced rapid disease progression during first cycle, and discontinued treatment prematurely. Conclusion: This ongoing study of RP6530 demonstrated an acceptable safety profile at doses evaluated, with a promising clinical activity. The results support further evaluation of RP6530 in pts with mature T-cell neoplasms. Disclosures Oki: Novartis: Research Funding. Barde:Rhizen Pharmaceuticals SA: Employment. Penmetsa:Rhizen Pharmaceuticals SA: Employment. Viswanadha:Incozen Therapeutics: Employment.

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Phase I Study of E7777, a Diphtheria Toxin Fragment-Interleukin-2 Fusion Protein, in Japanese Patients with Relapsed or Refractory Peripheral and Cutaneous T-Cell Lymphoma

Blood ◽

10.1182/blood.v126.23.2724.2724 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2724-2724 ◽

Cited By ~ 4

Author(s):

Dai Maruyama ◽

Kensei Tobinai ◽

Kiyoshi Ando ◽

Ken Ohmachi ◽

Michinori Ogura ◽

...

Keyword(s):

T Cell ◽

Dose Level ◽

Research Funding ◽

Cell Lymphoma ◽

Phase 1 ◽

Interleukin 2 ◽

T Cell Lymphoma ◽

Cutaneous T Cell Lymphoma ◽

Cd25 Expression ◽

Dose Levels

Abstract Background: E7777 is a recombinant cytotoxic fusion protein composed of diphtheria toxin fragments A, B and human interleukin-2. E7777 has the same amino acid sequence as denileukin diftitox, approved in the USA for treatment of persistent or recurrent CD25 positive cutaneous T-cell lymphoma on 1999, but with improved purity and an increased percentage of active protein monomer species. Since the specific bioactivity of E7777 is 1.5-2 times higher than that of the prior less purified form, a phase 1 study of E7777 in Japanese patients (pts) with peripheral and cutaneous T-cell lymphoma (PTCL and CTCL) was conducted. Methods: This multicenter, phase 1, dose-escalation (3+3 design) study assessed the safety, maximum tolerated dose (MTD), recommended dose (RD), pharmacokinetics (PK), immunogenicity (IM) and anti-tumor activity in pts with relapsed or refractory PTCL and CTCL. E7777 was administered by IV infusion over 60 min on 5 consecutive days of every 21 day cycle (up to 8 cycles) at planned dose-levels of 6, 12, 15 and 18 μg/kg/day (with evaluation of intermediate dose levels if necessary). Premedication including systemic steroid was required. Dose-limiting toxicity (DLT) was evaluated during the first cycle and MTD was determined as the highest dose at which less than 2 of a total 6 pts experienced a DLT. In the event that 2 of 6 pts experienced DLTs in a dose level, an Independent Safety Committee (ISC) will be consulted on whether that dose can be considered the MTD. Anti-tumor activity was evaluated by IWG-2007 criteria (only CT assessment) for PTCL and mSWAT for CTCL. Tumor CD25 expression was examined by immunohistochemistry in pts with available archival samples. Results: A total of 13 pts were enrolled at E7777 dose-levels of 6, 9 and 12 μg/kg/day. 10 pts had PTCL [PTCL-not otherwise specified (NOS), n=4; angioimmunoblastic T-cell lymphoma (AITL), n=3; anaplastic large cell lymphoma (ALCL)-ALK positive, n=1; ALCL-ALK negative, n=1; enteropathy-associated T-cell lymphoma, n=1] and 3 had CTCL [mycosis fungoides (MF), n=3]. The median age was 64 years (range 23-75), and the median number of prior chemotherapy regimens (excluding PUVA, interferon, retinoid) was 1 (range 0-8). DLTs were observed in 3 of 3 pts in the 12 μg/kg/day cohort; ALT increased, hyponatremia, hypokalemia and lymphopenia in one pt, ALT increased, fatigue, hypoalbminemia, hyponatremia and rash in another, and lipase increased in the third. This dose-level was considered to exceed the MTD and the 9 μg/kg/day dose level was expanded. Per recommendation of the ISC, the DLT definition was modified to not include lymphopenia, Grade 3 abnormality of hepatic enzyme recovered to Grade 2 or lower within cycle 1, and any other Grade 3 clinical abnormal laboratory result without clinical symptoms recovered within 7 days. Two of 6 pts in 9 μg/kg/day cohort experienced DLT of decreased appetite and fatigue, respectively. These events were recovered from within 2-3 weeks while interrupting the treatment. Per protocol, the ISC evaluated the toxicity profile of all the pts, and recommended the MTD and RD to be 9 μg/kg/day. As of 10 May 2015, the common adverse events (AEs) were ALT increased (85%), AST increased (77%), decreased appetite (77%), fatigue (77%), lymphopenia (77%), hypoalbuminemia (69%) and nausea (62%). Serious AEs considered related to study drug were reported in 3 pts; ALT increased, AST increased and fatigue in one pt, decreased appetite and hypoxia in another, and delirium in the third. AEs leading to study discontinuation were reported in 3 pts; AEs were hypersensitivity, respiratory failure (not related) and delirium. Objective response rate as assessed by investigator was 38% (5/13 pts), including response in 4 of 10 pts with PTCL and 1 of 3 pts with CTCL. All responses were PRs including 2 pts (AITL) at 6 μg/kg/day, 1 pt (MF) at 12 μg/kg/day followed by 6 μg/kg/day from 2nd cycle, and 2 pts (PTCL-NOS) at 9 μg/kg/day. Tumor responses were observed regardless of the level of CD25 expression in tumors. PK and IM data will be presented. Conclusions: The MTD and RD of E7777 was 9 μg/kg/day. The common AEs observed were considered manageable. Tumor responses were observed in PTCL, which firstly demonstrated with E7777, and also for CTCL pts regardless of level of tumor CD25 expression. Subsequent phase 2 study to evaluate the efficacy and safety of E7777 in pts with PTCL and CTCL, including evaluation of the relationship with CD25 expression, is warranted. Disclosures Maruyama: Takeda Pharmaceutical Company Limited: Honoraria; Eisai Co., Ltd.: Honoraria. Tobinai:Gilead Sciences: Research Funding. Ando:Eisai Co., Ltd.: Honoraria, Research Funding. Ogura:Kyowa Hakko Kirin co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Zenyaku Kogyo Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Phizer Japan Inc.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding; GlaxoSmithKline K.K.: Research Funding; MSD K.K.: Research Funding; AstraZeneca K.K.: Research Funding; Takeda Pharmaceutical Company Limited: Research Funding; Symbio Pharmaceuticals Limited: Research Funding; Solasia Phama K.K.: Research Funding; Mundipharma K.K.: Research Funding; Celgene K.K.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding. Uchida:Eisai Co., Ltd.: Research Funding. Nakanishi:Eisai Co., Ltd.: Employment. Namiki:Eisai Co., Ltd.: Employment.

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Final Results of Phase 1/1b Study of Tenalisib, Dual PI3K δ/γ Inhibitor in Patients with Relapsed/Refractory T-Cell Lymphoma

Blood ◽

10.1182/blood-2019-123954 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2831-2831 ◽

Cited By ~ 1

Author(s):

Swaminathan P. Iyer ◽

Brad M. Haverkos ◽

Jasmine Zain ◽

Radhakrishnan Ramchandren ◽

Mary Jo Lechowicz ◽

...

Keyword(s):

T Cell ◽

Adverse Events ◽

Board Of Directors ◽

Dose Escalation ◽

Safety Profile ◽

Research Funding ◽

Cell Lymphoma ◽

Phase 1 ◽

Clinical Activity ◽

Advisory Committees

Introduction: Tenalisib (RP6530) is a novel, highly specific, dual PI3K δ/γ inhibitor with nano-molar inhibitory potency at the enzyme and cellular level. PI3K plays a critical role in T-cell development and activation and several studies have validated the PI3K-AKT pathway as a potential therapeutic target in T cell lymphomas. Preliminary results of the ongoing Phase 1/1b T-cell lymphoma (TCL) study demonstrated an acceptable safety profile with encouraging clinical activity in relapsed/refractory TCL (Oki, ASCO 2018 and Iyer, ASH 2018). We now present the final results of the study (NCT02567656). Methods: This study comprised of four-dose escalation cohorts, followed by two dose expansion cohorts at MTD enrolling 20 patients each in PTCL and CTCL cohorts. Patients had histologically confirmed TCL, ECOG PS ≤2, and had received ≥1 prior therapy. Patients received Tenalisib [200 mg BID-800 mg BID (fasting), 800 mg (fed only)] orally until progression or unacceptable toxicity. The primary objectives were to determine the MTD and pharmacokinetic profile. The secondary objective was to evaluate overall response rate (ORR) and duration of response. Responses were evaluated for PTCL and CTCL based on IWG criteria (Cheson 2007) and mSWAT respectively. Adverse events were graded according to CTCAE v4.03. Results: Fifty-eight patients were enrolled in study, 19 in dose escalation and 39 in dose expansion (28 PTCL and 30 CTCL). Median number of prior therapies was 4 (range, 1-15). Safety assessment of 58 patients receiving at least one dose of Tenalisib demonstrated an acceptable safety profile. Treatment related Grade≥3 AEs were elevated ALT/AST (21%), rash (5%), and hypophosphatemia (3%). These events were reversible and managed by withholding study drug. Additionally, in few patients (N=9), steroids were used to manage elevated ALT/AST. There were six treatment related serious adverse events, none of these led to fatal outcome. At end of the study, four (3 CTCL; 1 PTCL) patients who completed minimum 8 cycles of therapy were rolled over to a compassionate use study (NCT03711604) and were followed up. Efficacy assessments demonstrated an ORR of 46% (3 CR and 13 PR) and clinical benefit rate (CR+PR+SD) of 77%. Subset efficacy analysis showed an ORR in PTCL of 47% (3 CR; 4 PR) and in CTCL of 45% (9 PR). The median time to initial response was 1.8 months and was similar in both sub-types. The overall median DOR was 4.91 months (range 0.9-26.6); in PTCL patients the DOR was 6.53 months, (range: 0.97-21.0) and 3.8 months (range: 1.67-25.67) in CTCL patients. In 3 PTCL patients who achieved CR, the median DOR was 19.5 months (range 7.5-21). Conclusion: Tenalisib demonstrated promising clinical activity and an improved safety profile in patients with relapsed/ refractory TCL. Currently, a phase I/II combination study to further evaluate safety and efficacy with romidepsin is ongoing in this target population. Disclosures Iyer: Arog: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Research Funding; Seattle Genetics, Inc.: Research Funding; Genentech/Roche: Research Funding; Incyte: Research Funding. Zain:Spectrum: Consultancy; Seattle Genetics: Consultancy. Korman:Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Glaxo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Immune Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa: Research Funding; Leo: Research Funding; Menlo: Research Funding; Merck: Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau; Pfizer: Research Funding; Principia: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Research Funding; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Rhizen: Research Funding; Sun: Honoraria, Membership on an entity's Board of Directors or advisory committees; Syntimmune: Research Funding; UCB: Research Funding; Valeant: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Dermira: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Routhu:Rhizen Pharmaceuticals S.A.: Employment. Barde:Rhizen Pharmaceuticals S.A.: Employment. Nair:Rhizen Pharmaceuticals S.A.: Employment. Huen:Galderma Inc: Research Funding; Glaxo Smith Kline Inc: Research Funding; Rhizen Pharmaceuticals: Research Funding; Innate Pharmaceuticals: Research Funding.

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