The Therapy Acceleration Program® (TAP) identifies and funds innovative projects related to therapies, supportive care or diagnostics that have the potential to change the standard of care for patients with blood cancer, especially in areas of high unmet medical need.
TAP funding assists both clinical investigators and companies in gaining critical clinical proof of concept data that better enables them to obtain the resources they need or a partner to complete the testing, registration and marketing of new treatments, supportive care and diagnostics for leukemia, lymphoma and myeloma.
TAP funding is different from the traditional grant at LLS. The TAP review process is separate from the grant process and each approved project is closely monitored by TAP staff.
Stemline Therapeutics, Inc. (Nasdaq:STML) announced an agreement with the U.S. Food and Drug Administration (FDA) on the registration pathway for SL-401 in blastic plasmacytoid dendritic cell neoplasm (BPDCN). To support the filing of a Biologics License Application (BLA) for full approval in first-line BPDCN, Stemline is currently enrolling an additional small cohort, planned for 8-12 first-line BPDCN patients, into its ongoing Phase 2 trial. To date, approximately half of these new patients are enrolled into the study, with full enrollment expected this quarter. Stemline intends to file a BLA in 2H17, which is anticipated to undergo an expedited review given SL-401's Breakthrough Therapy Designation. If successful, Stemline projects a commercial launch of SL-401 in 2018.
Kite Pharma, Inc. (Nasdaq:KITE) presented results from the ZUMA-1 trial of axicabtagene ciloleucel (KTE-C19) in patients with chemorefractory aggressive non-Hodgkin lymphoma (NHL) in two oral presentations at the American Society of Hematology (ASH) 58th Annual Meeting in San Diego, California.
ZUMA-1 enrolled 111 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL). Patients were required to have chemorefractory disease, defined as progressive or stable disease as best response to last line of therapy, or disease progression ≤12 months after autologous stem cell transplant. Manufacturing was successful for 110 patients, and 101 patients were treated. The pre-specified interim analysis was triggered when 51 patients with DLBCL had a minimum of three months of follow-up. At the time of interim analysis, 11 patients with PMBCL/TFL had been followed for three months. An additional 31 patients with one month of follow-up were included in the late breaker presentation.
ZUMA-1 met the primary endpoint of objective response rate (ORR), p < 0.0001. Response rates by disease subtype are shown in the table below. Responses were observed across key subgroups, including 75 percent CR in patients who relapsed in ≤12 months after autologous stem cell transplant and 47 percent CR in patients refractory to second line or later chemotherapy. At the month three assessment, 39 percent of patients were in CR.
The primary analysis of ZUMA-1 will include a minimum of 6 months of follow-up. Kite intends to seek regulatory approval of axicabtagene ciloleucel in refractory aggressive NHL and plans to complete its rolling submission of the Biologics License Application (BLA) in the first quarter of 2017.
Stemline Therapeutics, Inc. (Nasdaq:STML) announced the oral presentation of positive clinical data from its ongoing SL-401 Phase 2 potentially pivotal clinical trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN) at the 2016 American Society of Hematology (ASH) Annual Meeting, being held at the San Diego Convention Center in San Diego, CA.
The Phase 2 BPDCN data presented at ASH cover 32 evaluable adult BPDCN patients treated with SL-401. Results demonstrated that SL-401 produced a 100% (16/16) overall response rate (ORR), including an 81% (13/16) complete response (CR) rate in first-line BPDCN patients treated at the recommended dose of 12 ug/kg/day and a 95% (18/19) ORR in first-line patients treated at the recommended dose or lower. In relapsed/refractory patients, the ORR was 69% (9/13) with a CR rate of 31% (4/13).
|Line of Therapy||First-line||First-line||R/R||All lines|
|Dose Group||All Doses||12 ug/kg||12 ug/kg||All Doses|
|ORR||18/19 (95%)||16/16 (100%)||9/13 (69%)||27/32 (84%)|
|CR*, n (rate)||14 (74%)||13 (81%)||4 (31%)||18 (56%)|
|Bridged to SCT, n||6||6||1||7 (22%)|
Response duration data continue to appear promising, with 69% (11/16) first-line BPDCN patients treated at 12 ug/kg/day remaining relapse-free (range: 1+ to 20+ months, ongoing). In the relapsed/refractory setting, 46% (6/13) patients are relapse-free (range: 1+ to 7+ months). The median progression-free and overall survival for first-line has not been reached and for relapsed/refractory it is currently 8.5 months.
Kiadis Pharma N.V. (Euronext Amsterdam and Brussels: KDS) presented positive one-year data with its lead product ATIR101™ from the single dose Phase II trial (NCT01794299/EudraCT 2012-004461-41) at the 58th Annual Meeting and Exposition of the American Society of Hematology (ASH) in San Diego, United States of America.
The data presented at ASH confirms that ATIR101™ can be safely infused and shows a significant reduction in Transplant Related Mortality (TRM) (primary endpoint) and a significant improvement in Overall Survival (OS) (secondary endpoint) in comparison to an observational control group of patients undergoing a T-cell depleted haploidentical donor transplantation only. Combined with the lack of severe Graft-versus-Host-Disease (GVHD) and limited relapse, this translates into favorable GVHD-free, relapse-free survival (GRFS) one-year post-transplantation. Based on the positive results from this Phase II trial, the Company is proceeding with the development of ATIR101™ by initiating a Phase III trial in which patients with acute leukemia will be randomized to receive a haploidentical HSCT according to either the PTCy approach or the Kiadis Pharma approach with a single dose of ATIR101™. This Phase III trial has been submitted to regulatory authorities and is currently under review for approval.
Kite Pharma, Inc. (Nasdaq:KITE) announced that it has initiated the rolling submission with the U.S. Food and Drug Administration (FDA) of the Biologics License Application (BLA) for KTE-C19 as a treatment for patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant (ASCT). The pivotal ZUMA-1 study supporting this submission enrolled patients with chemorefractory diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL), three subtypes of aggressive NHL. The company expects to complete its BLA submission by the end of the first quarter of 2017.
Kite also announced that the United States Adopted Name, or USAN, for KTE-C19 will be axicabtagene ciloleucel. Axicabtagene ciloleucel (KTE-C19) received Breakthrough Therapy Designation (BTD) by the FDA in December 2015. If approved, Kite plans to commercially launch KTE-C19 in 2017.
Acetylon Pharmaceuticals announced that it has entered into an agreement to be acquired by Celgene Corporation. The acquisition will provide Celgene with, among other things, worldwide rights to Acetylon’s selective HDAC6 inhibitor programs and intellectual property in oncology, neurodegeneration, and autoimmune disease, including its lead drug candidates citarinostat (ACY-241) and ricolinostat (ACY-1215).
Since May 2011, The Leukemia & Lymphoma Society (LLS) Therapy Acceleration Program® has provided funding to help support Acetylon’s oral selective HDAC6 inhibitor drug candidates, ACY-1215 and ACY-241, in multiple myeloma.
Oncopep Inc. announced the initiation of a Phase 1b clinical trial evaluating PVX-410, a multi-peptide therapeutic cancer vaccine, in patients with moderate or high-risk for progression smoldering multiple myeloma (SMM), an asymptomatic precursor to multiple myeloma, which is a cancer of the plasma cells. The study, led by Noopur Raje, M.D. at Massachusetts General Hospital, will assess the safety and tolerability of PVX-410 in combination with durvalumab with or without lenalidomide. The trial initiation follows the successful completion of a Phase 1/2a dose escalation study of PVX-410 in patients with SMM, the results of which will be presented at the 58th Annual Meeting of the American Society of Hematology (ASH), being held from December 3-6, 2016 in San Diego, California.
In August of 2014, The Leukemia & Lymphoma Society (LLS) participated in the Series B financing which included participation from angel groups, family foundations and individuals. LLS’ decision to participate in the financing round resulted from a review of OncoPep’s application for funding from LLS' Therapy Acceleration Program®.
The University of Texas MD Anderson Cancer Center’s Institute for Applied Cancer Science (IACS) has initiated the first clinical study of a novel drug designed to starve cancer cells, IACS-10759. The study will enroll patients with acute myeloid leukemia (AML) and is supported by a $3.5 million investment from The Leukemia & Lymphoma Society (LLS) Therapy Acceleration Program®.
“LLS is going on the offensive against AML, a disease that has seen little change in the standard of care in more than 40 years,” said Lee Greenberger, Ph.D., LLS’s chief scientific officer. “Through our Beat AML initiative and other promising projects, such as this very innovative approach being developed by the MD Anderson team, we are hoping to change the paradigm of treatment for this deadly disease.”
Kite Pharma, Inc., (Nasdaq:KITE) announced positive topline results from a pre-planned interim analysis of ZUMA-1 for its lead product candidate, KTE-C19, in patients with chemorefractory diffuse large B-cell lymphoma (DLBCL). KTE-C19 met the primary endpoint of objective response rate (ORR), p < 0.0001, with ORR of 76 percent, including 47 percent complete remissions (CR). ZUMA-1 enrolled patients with chemorefractory aggressive NHL into two cohorts. Cohort 1 included patients with DLBCL, and Cohort 2 enrolled patients with transformed follicular lymphoma (TFL) and primary mediastinal B-cell lymphoma (PMBCL). Kite's intent is to seek regulatory approval of KTE-C19 in DLBCL, TFL and PMBCL based upon the combined data of both cohorts.
"ZUMA-1 enrolled patients with chemorefractory aggressive NHL, a disease that is very difficult to treat. The combined CR rate of 39 percent at three months is very exciting as it represents nearly a five-fold increase from the CR rate of 8 percent seen in the SCHOLAR-1 study in a similar patient population," said Jeff Wiezorek, M.D., Senior Vice President of Clinical Development. "ZUMA-1 is the largest CAR-T study reported in NHL. We were able to manufacture KTE-C19 for 99 percent of patients enrolled in the study, and successfully handle the study logistics and adverse event management at over 20 sites, most of which had no prior experience in CAR-T therapy."
Additional data from this interim analysis will be submitted for presentation at an upcoming scientific meeting. The primary analysis of 101 patients with chemorefractory aggressive NHL (DLBCL, TFL and PMBCL) will include approximately six months of follow-up and is expected in the first quarter of 2017. ZUMA-1 is supported in part by funding from The Leukemia & Lymphoma Society (LLS) Therapy Acceleration Program®.
Kiadis Pharma N.V. (Euronext Amsterdam and Brussels: KDS) announced that its partnership with The Leukemia & Lymphoma Society (LLS) has been strengthened with a second equity investment by LLS into the development of Kiadis Pharma’s lead product ATIR101™. LLS initially invested approximately US $1 million in February 2016 through an equity investment via its Therapy Acceleration Program®, a strategic initiative to partner directly with biotechnology companies to help accelerate the development of promising therapies. This second investment will now also be used to finance Kiadis Pharma’s second ongoing Phase II trial in leukemia patients which the Company then intends to continue into a randomized controlled Phase III pivotal study on track to start later this year. The ongoing Phase II trial is investigating the repeated dosing of ATIR101™ as an adjunctive treatment to a T-cell depleted haploidentical hematopoietic stem cell transplantation (HSCT) (donor cells from a half-matched related donor) in adult patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). The trial (CR-AIR-008; NCT02500550 / EudraCT 2015-002821-20) is conducted under an IND of the United States Food and Drug Administration and is set up to enroll patients in the United States as well as other countries, including Canada, Belgium and the United Kingdom.
Kite Pharma, Inc. (Nasdaq: KITE) announced that it has completed enrollment of 72 patients in DLBCL cohort in the Phase 2 portion of ZUMA-1. Kite looks forward to announcing top-line data from the first 50 DLBCL patients in the ZUMA-1 study, and, subject to these results, plan on submitting a Biologics License Application (BLA) with the U.S. Food and Drug Administration by the end of 2016.
The Leukemia & Lymphoma Society (LLS) and Kite Pharma entered into a partnership in July 2015 to enhance the development of Kite's lead product candidate, KTE-C19, for the treatment of patients with refractory aggressive non-Hodgkin lymphoma (NHL). LLS will launch a broad scope educational program focusing on CAR T-cell therapy for the treatment of blood cancers, as well as support outreach for clinical trial enrollment. LLS also will contribute up to $2.5 million, through the Therapy Acceleration Program®, to help fund Kite's ongoing Phase 1/2 clinical study of KTE-C19 (ZUMA-1; NCT02348216), which is designed to evaluate safety and efficacy in the treatment of patients with refractory diffuse large B cell lymphoma (DLBCL), as well as two rare lymphomas - primary mediastinal B cell lymphoma (PMBCL) and transformed follicular lymphoma (TFL).
Affimed N.V. (Nasdaq:AFMD) has reported that the Company’s IND application for a Phase1b AFM13/ KEYTRUDA® (pembrolizumab) combination study in HL patients relapsed or refractory to chemotherapy, including Adcetris™ (NCT02665650), has recently been accepted by the FDA and is now active. The first sites have been opened and the study is recruiting. The Company anticipates providing a first update on the study by the end of 2016 or in the first quarter of 2017.
The Leukemia & Lymphoma Society (LLS) and Affimed N.V. entered into a partnership to co-fund a phase 2 trial with the Recruit-TandAb AFM13, a novel tetravalent bispecific antibody directed against human CD30 and CD16A in Hodgkin Lymphoma (HL) patients for whom currently available treatments have failed. AFM13 is a first-in-class immunotherapy drug designed to treat HL patients and patients with CD30-positive malignancies. LLS has committed to investing up to $4.4 million over 2 years to support the project.
Kite Pharma, Inc. (Nasdaq:KITE) ("Kite") presented via a poster presentation at the 2016 American Society of Clinical Oncology (ASCO) annual meeting the updated durability of complete responses in the Phase 1 portion of the ZUMA-1 trial. "Three reported complete remissions in patients with chemorefractory DLBCL after a single treatment with CAR T-cell therapy are still ongoing at nine months. This is remarkable given that single-digit complete response rates are historically observed in patients who do not respond to chemotherapy," said Sattva S. Neelapu, Associate Professor and Director of Translational Research, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center. "These results are extremely important as CAR engineered T-cells have the potential to transform the treatment landscape for chemorefractory DLBCL."
The Phase 1 portion of ZUMA-1 treated a total of 7 patients with chemorefractory DLBCL. The results showed that treatment with KTE-C19 achieved rapid and durable responses in patients with chemorefractory disease (objective response rate 71%, complete response rate 57%). Ongoing complete responses were observed in 3 patients after nine months of follow-up. KTE-C19 related adverse events consisted predominantly of cytokine release syndrome (CRS) and neurotoxicity, which were generally reversible. Grade 3 or higher CRS was observed in 14% and neurotoxicity in 57%; all were reversible except in one patient with dose-limiting toxicity.
The Leukemia & Lymphoma Society (LLS) and Kite Pharma, Inc. entered into a partnership to enhance the development of Kite's lead product candidate, KTE-C19, for the treatment of patients with refractory aggressive non-Hodgkin lymphoma (NHL). Under the collaboration, LLS will launch a broad scope educational program focusing on CAR T-cell therapy for the treatment of blood cancers, as well as support outreach for clinical trial enrollment. LLS also will contribute up to $2.5 million, through the Therapy Acceleration Program®, to help fund Kite's ongoing Phase 1/2 clinical study of KTE-C19 (NCT02348216).
Stemline Therapeutics, Inc. (Nasdaq:STML) presented via an oral presentation at the 2016 American Society of Clinical Oncology (ASCO) annual meeting the positive clinical data from its ongoing SL-401 Phase 2 potentially pivotal clinical trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN). Results demonstrate that SL-401 produced an 89% (17/19) overall response rate (ORR) in BPDCN, with a 100% (12/12) ORR in first-line patients and a 71% (5/7) ORR in relapsed/refractory patients. In 12 evaluable first-line patients (all doses), there were 9 complete responses (CR) and 2 clinical complete responses (CRc). CRc is defined as a CR in non-skin affected organs with marked gross clearance of skin lesions and residual microscopic skin disease. In the 10 evaluable first-line patients treated at 12 ug/kg/day, the CR/CRc rate was 100% (8 CR and 2 CRc). In the 7 evaluable relapsed/refractory BPDCN patients, including one treated on a compassionate use basis, the ORR rate was 71%, which included 1 CR and 1 CRc (29% CR/CRc rate) and 3 partial responses (PR). The study (NCT02113982) is sponsored in part by The Leukemia & Lymphoma Society's Therapy Acceleration Program®. Please click here for a video to hear from Dr. Naveen Pemmaraju, where he discusses early results from an ongoing trial of SL-401 in patients with the rare, aggressive malignancy BPDCN.
Kiadis Pharma N.V. (Euronext Amsterdam and Brussels: KDS) announced a regulatory strategy update that, based on positive Phase II data, it has taken the decision to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for its lead product ATIR101™ for use in blood cancers to reduce relapse rates, Transplant Related Mortality (TRM) and Graft-versus-Host-Disease (GVHD) in the context of a hematopoietic stem cell transplantation using a haploidentical donor. The Company will now start compiling an MAA document and anticipates submitting the application to EMA in Q1, 2017.
Kite Pharma, Inc. (Nasdaq:KITE) announced that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) and Committee for Advanced Therapies (CAT) has granted access to its newly established Priority Medicines (PRIME) regulatory initiative for KTE-C19 in the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). PRIME provides early and enhanced regulatory support to optimize regulatory applications and speed up the review of medicines that address a high unmet need. Access to the Priority Medicines initiative is granted by the EMA to support the development and accelerate the review of new therapies to treat patients with unmet medical need. The criteria for the Priority Medicines initiative require early clinical evidence that the therapy offers a therapeutic advantage over existing treatments or benefits patients without treatment options. This designation provides appointment of a rapporteur, early dialogue and scientific advice at key development milestones, and the potential to qualify products for accelerated review earlier in the application process. The U.S. Food and Drug Administration granted Breakthrough Therapy Designation to KTE-C19 for the treatment of patients with DLBCL, primary mediastinal B-cell lymphoma (PMBCL), and transformed follicular lymphoma (TFL) in December 2015.
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) and Celator Pharmaceuticals, Inc. (Nasdaq: CPXX) announced on May 31 2016 that they have entered into a definitive agreement for Jazz Pharmaceuticals to acquire Celator for $30.25 per share in cash, or approximately $1.5 billion. The transaction is expected to close in the third quarter of 2016.
Celator Pharmaceuticals, Inc. announced that the United States Food and Drug Administration (FDA) granted Breakthrough Therapy designation to VYXEOS (also known as CPX-351). VYXEOS is an investigational product in development as a treatment for AML and other blood cancers. The Breakthrough Therapy designation is primarily based upon the positive results from the pivotal Phase 3 clinical trial in older patients with previously untreated high-risk (secondary) AML. The designation is for the treatment of adults with therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC). This designation includes the patient populations enrolled in the Phase 3 clinical trial. The Phase 3 trial met its primary endpoint demonstrating a statistically significant improvement in overall survival. Data will be presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting on Saturday, June 4th. FDA awards Breakthrough Therapy designation in order to expedite the development and review of new medicines that are intended to treat serious or life-threatening diseases when the therapy has demonstrated substantial improvement over available therapies on at least one clinically significant endpoint or when there is significant unmet medical need. Celator plans to submit a New Drug Application (NDA) to the FDA by the end of the third quarter of 2016.
Kiadis Pharma N.V. announced positive results on the primary endpoint of its single dose Phase II trial (NCT01794299/EudraCT 2012-004461-41) with its lead product ATIR101™ at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation (EBMT) in Valencia, Spain. The data confirms that ATIR101™ can be safely infused, does not cause grade III-IV Graft-versus-Host-Disease (GVHD) and shows a significant reduction in Transplant Related Mortality (TRM) and a significant improvement in Overall Survival (OS) in comparison to a historical control group of patients undergoing a T-cell depleted haploidentical donor transplantation only. Based on the positive results from this Phase II trial, the Company will proceed with the development of ATIR101™ as an adjunctive immuno-therapeutic treatment to a haploidentical HSCT for patients with acute leukemia, initiating a randomised Phase III trial in the second half of 2016.
Kiadis previously entered into a partnership with The Leukemia & Lymphoma Society (LLS) under which LLS is investing via its Therapy Acceleration Program® (TAP) through an equity investment of approximately $1 million for the Phase II development investigating the repeated dosing of ATIR101™. This ongoing Phase II trial (CR-AIR-008; NCT02500550) is set up to enroll patients in the United States as well as other countries, including Canada, Belgium and the United Kingdom.
Celator Pharmaceuticals, Inc. announced positive results from the Phase 3 trial of VYXEOS™ (cytarabine: daunorubicin) Liposome for Injection (also known as CPX-351) in patients with high-risk (secondary) acute myeloid leukemia (AML) compared to the standard of care regimen of cytarabine and daunorubicin known as 7+3. The trial met its primary endpoint demonstrating a statistically significant improvement in overall survival. The median overall survival for patients treated with VYXEOS in the study was 9.56 months compared to 5.95 months for patients receiving 7+3, representing a 3.61 month improvement in favor of VYXEOS. The hazard ratio (HR) was 0.69 (p=0.005) which represents a 31 percent reduction in the risk of death versus 7+3. The percentage of patients alive 12 months after randomization was 41.5% on the VYXEOS arm compared to 27.6% on the 7+3 arm. The percentage of patients alive 24 months after randomization was 31.1% on the VYXEOS arm compared to 12.3% on the 7+3 arm. Based on these results the company expects to submit a New Drug Application (NDA) for VYXEOS with the U.S. Food and Drug Administration (FDA) later this year and submit a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) in the first quarter of 2017. The study was conducted in partnership with The Leukemia & Lymphoma Society® (LLS) through its Therapy Acceleration Program® (TAP), which has supported the clinical development of VYXEOS beginning in Phase 2.
Valor Biotherapeutics, LLC announced that the first patient was dosed in a phase 1 clinical study of its lead product candidate, IGN002, a novel investigational treatment for non-Hodgkin lymphoma (NHL). Valor, a joint venture between ImmunGene and Caliber Biotherapeutics, has partnered with The Leukemia & Lymphoma Society (LLS) on the pre-clinical development, manufacturing, and initial proof-of-concept clinical study of IGN002. Data from pre-clinical studies of IGN002 were presented at the American Society of Hematology meeting in December 2015.
Clinical Trials in Partnership with LLS
Both TAP and LLS research grant fundings are critical in supporting many active clinical trials at any given time. The ClinicalTrials.gov website provides an updated listing of clinical trials where LLS is listed as a collaborator. ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. More information about the clinical trials in partnership with LLS TAP can also be found within each TAP division found below.
How TAP Works
The program comprises three divisions, each with designated strategies, to speed the development of blood cancer treatments, supportive care and diagnostics: