On December 11, 2017 Seattle Genetics, Inc. (NASDAQ:SGEN) and Bristol-Myers Squibb Company (NYSE:BMY) reported highlighted updated interim results from an ongoing phase 1/2 clinical trial evaluating the combination of ADCETRIS (brentuximab vedotin) and Opdivo (nivolumab) in relapsed or refractory classical Hodgkin lymphoma (HL) at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in Atlanta, Georgia, December 9-12, 2017 (Press release, Seattle Genetics, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322109 [SID1234522562]). The data were also simultaneously published online in the journal Blood. The data reported from 62 patients, including 60 evaluable for response, were featured in an oral presentation and selected to be included in the 2018 Highlights of ASH (Free ASH Whitepaper) post-meeting program. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL that plays a role in tumor growth and survival. Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to harness the body’s own immune system to help restore anti-tumor immune response. ADCETRIS and Opdivo are not approved in combination for the treatment of relapsed or refractory HL or for other indications.

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"The phase 1/2 study combining the antibody-drug conjugate ADCETRIS with the PD-1 immune checkpoint inhibitor Opdivo is a promising investigational approach as it combines a CD30-targeted therapy with a therapy designed to activate the immune system. The antitumor activity of the drugs may be enhanced when administered in combination," said Alex Herrera, M.D., lead trial investigator and assistant professor at the City of Hope Medical Center, Duarte, California. "The interim results evaluating the combination regimen in relapsed or refractory HL patients continue to look compelling, demonstrating both promising activity in addition to a manageable overall safety profile. These data support further exploration of this novel, chemotherapy-free investigational regimen in HL patients."

"We are evaluating ADCETRIS broadly as the foundation of care for CD30-expressing lymphomas, including combination strategies that have the potential to improve efficacy. At this year’s ASH (Free ASH Whitepaper) Annual Meeting, we are presenting significant clinical updates that support this goal, including results from the phase 3 ECHELON-1 clinical trial evaluating ADCETRIS in combination with chemotherapy in frontline HL as well as interim results from this phase 1/2 study evaluating ADCETRIS in combination with Opdivo in relapsed HL," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "Interim results from the trial evaluating ADCETRIS in combination with Opdivo as pre-transplant salvage therapy for classical HL patients continue to look promising, demonstrating an 83 percent objective response rate, with a 62 percent complete response rate and an acceptable safety profile. We look forward to further evaluation of this innovative combination regimen in other disease settings, including the ongoing pivotal phase 3 CHECKMATE 812 study in patients with relapsed HL, in partnership with Bristol-Myers Squibb."

"Our ongoing collaboration to evaluate Opdivo in combination with Seattle Genetics’ ADCETRIS reinforces Bristol-Myers Squibb’s commitment to addressing cancer from all angles for patients with high unmet needs," said Fouad Namouni, M.D., head of Oncology Development, Bristol-Myers Squibb. "We look forward to further evaluation of the ADCETRIS and Opdivo combination in Hodgkin lymphoma and other hematologic malignancies in several ongoing trials."

Interim Results from a Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #649, oral presentation at 10:30 a.m. ET)

Data were reported from 62 patients with relapsed or refractory HL who received the combination regimen of ADCETRIS plus Opdivo after failure of frontline therapy. Patients were treated once every three weeks, with up to four cycles of combination therapy in the outpatient setting. After completion of the fourth cycle of treatment, patients were eligible to undergo an autologous stem cell transplant (ASCT). The median age of patients was 36 years. The majority of patients (95 percent) were refractory or had relapsed after receiving the standard of care frontline treatment ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) or some variation of the standard of care (ABVE-PC, R-ABVD).

Key findings presented include:

Of 60 response-evaluable patients, 50 patients (83 percent) had an objective response, including 37 patients (62 percent) with a complete response and 13 patients (22 percent) with a partial response. Five patients (eight percent) had stable disease and five patients (eight percent) had progressive disease. Median follow-up time was eight months and median duration of response was not yet reached. The estimated six-month progression-free survival rate was 89 percent.
Of the 62 patients enrolled, 58 patients completed all four cycles of study treatment and four patients discontinued prior to the end of treatment. At the time of data analysis, 54 patients received an ASCT. Preliminary analysis shows no impact of combination treatment with ADCETRIS and Opdivo on stem cell mobilization or engraftment.
The most common adverse events (AEs) of any grade occurring prior to ASCT or subsequent salvage therapy in at least 20 percent of patients were nausea, fatigue, infusion-related reaction (IRR), pruritus, diarrhea, headache, cough, vomiting, dyspnea, nasal congestion, pyrexia and rash. Grade 3 or 4 adverse events occurred in 19 patients (31 percent), with 17 patients (28 percent) having Grade 3 AEs (fatigue, IRR, pruritus and diarrhea) and two patients (three percent) having Grade 4 AEs (thrombocytopenia and increased lipase).
Infusion-related reactions (IRRs) were observed in 44 percent of patients, of which the majority (41 percent) were Grade 1 or 2. No patients discontinued treatment due to an IRR.
Potential immune-related adverse events, excluding IRRs, occurred in 50 patients (82 percent), and five patients required treatment with systemic steroids, including patients with Grade 3 diarrhea and Grade 2 colitis, Grade 3 aspartate aminotransferase elevation, Grade 4 colitis and pneumonitis (after receiving additional salvage therapy), Grade 2 pneumonitis, and Grade 4 pneumonitis (after BEAM, as part of the conditioning regimen). No patients discontinued treatment due to an immune-related adverse event.
ADCETRIS and Opdivo are being evaluated as combination therapy in multiple ongoing clinical trials. In addition to the study presented at ASH (Free ASH Whitepaper), a trial titled "A Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas" is ongoing and enrolling patients with relapsed or refractory disease, including diffuse large B-cell lymphoma (DLBCL), and other rare subtypes of B-cell lymphoma, including mediastinal B-cell lymphoma and mediastinal gray zone lymphoma. The companies have also extended the clinical evaluation of ADCETRIS and Opdivo into a clinical trial evaluating the combination as frontline treatment for older HL patients. Lastly, the companies initiated a pivotal phase 3 clinical trial called CHECKMATE 812 trial evaluating ADCETRIS alone versus ADCETRIS in combination with Opdivo in relapsed/refractory HL patients.

About Classical Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system and is the most common type of blood cancer. There are two major categories of lymphoma: HL, also known as Hodgkin disease, and non-Hodgkin lymphoma. HL is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. The disease is most often diagnosed in early adulthood (ages 20-40) and late adulthood (older than 55 years of age). Classical Hodgkin lymphoma is the most common type of HL, accounting for 95% of cases. Classical HL is distinguished from other lymphomas by the characteristic presence of CD30-positive Reed-Sternberg cells.

According to the American Cancer Society, approximately 8,260 cases of Hodgkin lymphoma will be diagnosed in the United States during 2017 and more than 1,000 will die from the disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.

About ADCETRIS

ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 and is being evaluated broadly in more than 70 clinical trials, including three phase 3 studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma that supported the recent FDA Breakthrough Therapy Designation and submission of the supplemental Biologics License Application (BLA) for use in this setting, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for four indications: (1) regular approval for adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, (2) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (3) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (4) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-ASCT consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. The European Commission extended the current conditional marketing authorization of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.

ADCETRIS has received marketing authorization by regulatory authorities in 69 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo + Yervoy combination was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

On December 11, 2017 Verastem, Inc. (NASDAQ: VSTM), focused on discovering and developing drugs to improve the survival and quality of life of cancer patients, reported the presentation of new preclinical and Phase 1 clinical data from an investigator-sponsored study evaluating the safety and activity of oral duvelisib in combination with romidepsin (Istodax) or bortezomib (Velcade) in relapsed or refractory T-cell lymphomas (TCL) at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2017 Annual Meeting held December 9-12, 2017 in Atlanta (Press release, Verastem, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322203 [SID1234522563]). Duvelisib is a first-in-class oral dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma which is currently being developed for the treatment of relapsed or refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) and Follicular Lymphoma (FL). In addition, duvelisib is being studied in other hematologic malignancies including both peripheral and cutaneous T cell lymphoma (TCL).

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"The data presented today at ASH (Free ASH Whitepaper) demonstrate that oral duvelisib, combined with either romidepsin or bortezomib, has an acceptable safety profile in patients with relapsed or refractory TCL with response rates, while still preliminary, that appear promising when compared to those seen with currently approved therapies," said Steven Horwitz, MD, Memorial Sloan Kettering Cancer Center (MSKCC), co-principal investigator of the Phase 1 study, and lead author of the oral presentation. "We were especially pleased to see that these response rates were even higher in patients with peripheral TCL (PTCL), a rare and aggressive type of non-Hodgkin lymphoma. These clinical results were further bolstered by important preclinical findings showing duvelisib’s cell killing activity in vitro and its ability to promote beneficial changes within the in vivo tumor microenvironment."

"The preclinical and Phase 1 results reported today by the team at MSKCC are important because they provide further validation for our continued expansion of the duvelisib development program into T-cell malignancies including PTCL," said Diep Le, MD, PhD, Chief Medical Officer of Verastem. "Overall, our data presentations at ASH (Free ASH Whitepaper) this year continue to build upon the strong foundation of preclinical research and clinical investigation for Verastem’s product candidates, demonstrating their anti-cancer activity, either alone or in combination with other agents, across a wide variety of hematologic malignancies."

Phase 1 Safety and Activity Results
This multicenter, Phase I trial is comprised of parallel arms evaluating oral duvelisib in combination with romidepsin (arm A) or bortezomib (arm B) in patients with relapsed/refractory TCL, including PTCL and cutaneous T-cell lymphoma (CTCL). Oral duvelisib was dosed at 25mg, 50mg, or 75mg twice-daily (BID) on days 1-28. Romidepsin 10mg/m2 was dosed on Days 1, 8, and 15 (arm A) or bortezomib 1mg/m2 on Days 1, 4, 8, and 11 (arm B), both cohorts on 28-day cycles.

In arm A, there were 15 patients evaluable for efficacy (PTCL, n=11; CTCL, n=4). Of these, nine responded (4 complete responses (CR) and 5 partial responses (PR) for an overall response rate (ORR) of 60%. Seven of the 11 patients with PTCL responded (4 CR and 3 PR) for an ORR of 64%. Among the 9 patients evaluable for safety (25mg, n=3; 50mg, n=3; 75mg, n=3), there were no dose limiting toxicities (DLT), therefore oral duvelisib 75mg BID in combination with romidepsin 10mg/m2 IV was defined as the maximum tolerated dose (MTD). The most common Grade 1/2 adverse events were fatigue (n=9), nausea (n=8), altered taste (n=8) and diarrhea (n=6), rash (n=5), dysphagia (n=4) and anorexia (n=4). The most common Grade 3/4 adverse events were neutropenia (n=6), thrombocytopenia (n=1), lung infection (n=1), pleural effusion (n=1) and hyponatremia (n=1). There were two deaths (sepsis and diffuse alveolar hemorrhage following allogeneic stem cell transplant) that were both assessed as unrelated to study drug.

In arm B, there were 17 patients evaluable for efficacy (PTCL, n=10; CTCL, n=7). Of these, six responded (3 CRs and 3 PRs) for an ORR of 35%. Five of the 10 patients with PTCL responded (3 CRs and 2 PRs) for an ORR of 50%. Among the 14 patients evaluable for safety (25mg, n=6; 50mg, n=3; 75mg, n=5), there was one DLT (pneumonia) in the 25mg group. The MTD was determined to be oral duvelisib 25mg BID in combination with bortezomib 1mg/m2 IV. The most common Grade 1/2 adverse events were diarrhea/colitis (n=11), nausea/vomiting (n=4), chills (n=4) and fatigue (n=4). The most common Grade 3/4 adverse events were ALT and AST elevation (n=6), rash (n=2) and neutropenia (n=2). There was a case of Stevens-Johnson syndrome resulting in death which was assessed by the investigator as possibly related to bortezomib, duvelisib, and trimethoprim-sulfamethoxazole, a medication that was initiated at the start of the study.

A copy of this oral presentation will be available here following the conclusion of the session.

About the Tumor Microenvironment
The tumor microenvironment encompasses various cellular populations and extracellular matrices within the tumor or cancer niche that support cancer cell survival. This includes immunosuppressive cell populations such as regulatory T-cells, myeloid-derived suppressor cells, M2 TAMS, as well as tumor-associated fibroblasts and extracellular matrix proteins which can hamper the entry and therapeutic benefit of cytotoxic immune cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s compounds duvelisib and defactinib target the tumor microenvironment as a mechanism of action to potentially improve a patient’s response to therapy.

About Duvelisib
Duvelisib is a first-in-class investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B- and T-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage extension trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL),4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL).5 Both DUO and DYNAMO achieved their primary endpoints and Verastem intends to submit a New Drug Application (NDA) requesting the full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL, and accelerated approval for the treatment of patients with relapsed or refractory follicular lymphoma (FL). Duvelisib is also being developed by Verastem for the treatment of peripheral T-cell lymphoma (PTCL), and is being investigated in combination with other agents through investigator-sponsored studies.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov

About Focal Adhesion Kinase
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase encoded by the PTK-2 gene that is involved in cellular adhesion and, in cancer, metastatic capability. Defactinib (VS-6063) and VS-4718 are orally available compounds that are potent inhibitors of FAK. Defactinib and VS-4718 utilize a multi-faceted approach to treat cancer by reducing cancer stem cells, enhancing anti-tumor immunity, and modulating the local tumor microenvironment. Defactinib is currently being studied in multiple clinical trials for patients with cancer.

On December 11, 2017 Kite, a Gilead Company (Nasdaq: GILD), reported updated results from the ongoing Phase 1/2 ZUMA-3 study of KTE-C19, a CD19 chimeric antigen receptor T (CAR T) cell therapy, which is investigational for the treatment of adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) (Press release, Kite Pharma, DEC 11, 2017, View Source;p=irol-newsArticle&ID=2322221 [SID1234522565]). With a minimum of eight weeks of follow-up, 71 percent of ALL patients (n=17/24) who received a single infusion of KTE-C19 achieved complete tumor remission (complete remission (CR) or CR with incomplete hematological recovery). The ZUMA-3 study results were presented in an oral session at the Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta.

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This press release features multimedia. View the full release here: View Source

ALL is an aggressive type of blood cancer which can also involve the lymph nodes, spleen, liver, central nervous system and other organs.

"Approximately half of new ALL cases occur in adults age 20 or older and a majority of adult ALL patients relapse and have poor subsequent outcomes," said Bijal Shah, MD, ZUMA-3 investigator and medical oncologist, Moffitt Cancer Center, Tampa, Fla. "The deep remissions seen with these early study results offer promise that adults with this aggressive disease may benefit from personalized cell therapy with KTE-C19. Pending further clinical evaluation, this has the potential to be an advance for adults with no other treatment options."

ZUMA-3 is an ongoing multicenter Phase 1/2 study in patients with ALL whose disease is refractory to or has relapsed following standard chemotherapy or hematopoietic stem cell transplantation. The objectives of the study are to evaluate the safety and efficacy of KTE-C19 in this patient population.

At the time of data cutoff, 24 patients were evaluable for response. KTE-C19 demonstrated a 71 percent (n=17/24) rate of complete remission, with 100 percent of responders having no detectable minimal residual disease, including in those with high tumor burden and high risk genetic abnormalities.

In the safety analysis of 29 patients, adverse events were consistent with the known toxicities of CD19 CAR T treatment, including Grade 3 or higher cytokine release syndrome (CRS) and neurologic toxicities in 28 percent (n=8/29) and 52 percent of patients (n=15/29), respectively. Two patients receiving KTE-C19 died due to adverse events, including one patient with a cerebrovascular accident not related to KTE-C19 treatment approximately seven weeks after treatment and a previously reported patient who experienced fatal CRS.

"We believe personalized cell therapy has the potential to become a cornerstone of cancer treatment and are rapidly advancing CAR T studies in ALL and in other cancers," said David Chang, MD, PhD, Worldwide Head of Research and Development and Chief Medical Officer at Kite. "ZUMA-3 is reflective of our continued commitment to cell therapy cancer treatment and we are pleased to see these early results for people living with ALL."

KTE-C19 for ALL is investigational and has not been proven safe or efficacious.

On December 11, 2017 Gamida Cell, a leading cellular and immune therapeutics company, reported final results from the phase I/II trial evaluating NiCord, a product derived from cord blood stem cells, as a stand-alone graft to treat patients with high-risk hematologic malignancies (Press release, Gamida Cell, DEC 11, 2017, View Source [SID1234522566]). The study met its primary endpoint, demonstrating rapid neutrophil engraftment with manageable side effects. The company also presented preclinical data for the advancement of natural killer cells (NK cells) as an immunotherapeutic modality for patients with cancer. Both studies were presented today at the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta, GA.

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"We are enthusiastic about the data presented today at ASH (Free ASH Whitepaper), including the final results of our NiCord phase I/II study, which support the basis for our global phase III trial of NiCord versus standard unmanipulated cord blood transplantation (UCBT), currently enrolling patients with hematologic malignancies," said Julian Adams, Ph.D., chairman and chief executive officer of Gamida Cell. "We look forward to further evaluating the potential of NiCord to serve as the graft of choice for the thousands of patients with no matched donor in need of a transplant every year, as well as continuing to progress our other pipeline programs."

Final Data from Phase I/II Trial of NiCord.
The multicenter phase I/II study evaluated the safety and efficacy of NiCord as a stand-alone graft in 36 patients with high-risk hematologic malignancies, with a primary endpoint of time to neutrophil engraftment following transplantation. Despite varying blood cancer diagnoses and preparative conditioning regimens across patients across centers, improved results were seen in the majority of study participants treated with NiCord.

Final results of the study include the following:

Participants transplanted with NiCord had rapid and durable engraftment of neutrophils and platelets, as well as prompt immune reconstitution:
Median time to neutrophil engraftment was 11 days (95% CI: 9-13 days);
Median time to platelet engraftment was 34 days (95% CI: 32-42 days).
Results from the study participants were compared to a database of matched patients from the Center for International Blood and Marrow Transplant Research (CIBMTR). According to the CIBMTR data, patients who received UCBT had a median time to neutrophil engraftment of 21 days and a median time to platelet engraftment of 46 days.
NiCord demonstrated an acceptable safety profile, with moderate/severe chronic graft vs. host disease (cGvHD) in 9.8% of patients at one year following transplantation. By day 100, 20.2% of participants experienced grade 2-3 bacterial or grade 3 fungal infections.

"Historically, transplantation with cord blood has been limited due to slow engraftment time in patients. We are looking to address this gap, and this study demonstrated rapid and sustained engraftment in study participants by utilizing technology to expand the number of stem cord blood cells in a culture," said Mitchell Horwitz, M.D., principal investigator, co-study chair and professor of medicine at the Duke Cancer Institute. "These phase I/II data demonstrate the potential to make stem cell transplants accessible to a greater number of patients who do not have a matched donor."

Preclinical Data from NAM-NK Cell Program
Proof-of-concept data on the application of the company’s proprietary NAM technology to healthy donor natural killer cells (NK cells) as a potential immunotherapeutic approach to treating cancer were highlighted in an oral presentation.

"The use of NK cells as a modality for immunotherapy has been limited by impaired functionality of adoptively transferred NK cells in patients," said Ronit Simantov, M.D., chief medical officer at Gamida Cell. "We are encouraged by the study results, which demonstrated persistence and proliferation of NAM-NK cells in pre-clinical in vivo models and describe a reliable, scalable culture model for the expansion of functional donor NK cells aimed at clinical use."

The analysis, which combines data from multiple preclinical studies, validates the approach and is the basis for an investigator-sponsored, phase I clinical trial of NAM-NK Cells in patients with relapsed/refractory multiple myeloma or CD20-positive non-Hodgkin lymphoma.

About NiCord
NiCord, the company’s lead clinical program, is under development as a universal bone marrow transplant solution for patients with high-risk hematologic malignancies. NiCord has demonstrated improved efficacy over unmanipulated cord blood, including fewer bacterial and fungal infections and a reduction in duration of hospital stays. NiCord has been granted breakthrough status by the U.S. Food and Drug Administration, making it the first bone marrow transplant alternative to receive this designation. It has also received U.S. and EU orphan drug designation. The ongoing phase III study is evaluating NiCord as a curative treatment for patients with leukemia and lymphoma who have been indicated for an allogeneic stem cell transplant. For more information on NiCord clinical trials, please visit www.clinicaltrials.gov.

About NAM-NK Cells
Gamida Cell expanded the capabilities of its NAM technology to utilize NK cells to create an immunotherapy to treat patients with refractor blood cancers and solid tumors. Through expansion of highly functional NK cells using NAM technology, NAM-NK Cells can be used to harness the immune system to attack cancer. NAM-NK Cell is under phase I development (NCT03019666) in patients with relapsed or refractory B-cell lymphoma and multiple myeloma.

On December 11, 2017 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported new efficacy and safety data from the ongoing Phase 1 dose-escalation and expansion study evaluating oral ivosidenib (AG-120) in patients with relapsed or refractory acute myeloid leukemia (R/R AML) and an isocitrate dehydrogenase-1 (IDH1) mutation (Press release, Agios Pharmaceuticals, DEC 11, 2017, View Source [SID1234522571]). Ivosidenib is an investigational, first-in-class, oral, targeted inhibitor of the mutant IDH1 enzyme. Data in an oral session at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition demonstrated a complete response (CR) and CR with partial hematologic recovery (CRh) rate of 30.4% and an overall response rate (ORR) of 41.6% in the primary analysis set of 125 patients with R/R AML who received ivosidenib at 500 mg once daily and received their first dose at least 6 months prior to the May 12, 2017 analysis cutoff date. The CR+CRh rate is the primary endpoint of the study.

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"New ivosidenib data from the expansion phase of the Phase 1 study is compelling and demonstrates impressive single-agent efficacy with durable responses in these high-risk relapsed or refractory AML patients," said Courtney DiNardo, M.D., lead investigator and assistant professor, department of leukemia at the University of Texas MD Anderson Cancer Center. "Important measures of clinical benefit for patients treated with ivosidenib were also observed and include increases in transfusion independence and a decrease in the frequency of comorbidities such as febrile neutropenia and infections in responding patients."

A total of 258 patients with advanced hematologic malignances and an IDH1 mutation were treated on the Phase 1 study, which included 78 patients in the dose-escalation portion and 180 patients from four dose-expansion Arms. Enrollment to the study is closed. This is the first presentation of data from the dose-expansion portion of the study. Safety data reported include all treated patients, and includes those who received ivosidenib at total daily doses ranging from 200 mg to 1200 mg in dose-escalation and 500 mg daily in dose expansion. A maximum tolerated dose was not reached in the dose-escalation portion of the trial. The primary analysis set is comprised of 125 R/R AML patients (92 patients from Arm 1 of the expansion and 33 patients from the dose-escalation who met the eligibility criteria for Arm 1 and received ivosidenib at 500 mg once daily) who were enrolled at least 6 months prior to the primary analysis cutoff date of May 12, 2017. The median age of these patients is 67 (ranging from 18-87), and the median number of prior regimens is two (ranging from one to six).

"These data form the core of the efficacy analysis for our ivosidenib NDA submission, which is on track for the end of the year," said Chris Bowden, M.D., chief medical officer of Agios. "We believe that these data validate the potential for ivosidenib to be a first-in-class therapy for patients with R/R AML and an IDH1 mutation."

Safety Data
A safety analysis conducted for all 258 treated patients as of the data cut-off showed that ivosidenib continues to demonstrate a favorable safety profile. The most common adverse events (AEs) regardless of causality were diarrhea (33.3%), leukocytosis (30.2%), nausea (29.5%), fatigue (28.7%) and febrile neutropenia (25.2%).

Among the 125 R/R AML patients from the primary analysis set, adverse events of interest were the following:

8% reported Grade ≥3 leukocytosis, which was managed with hydroxyurea. No cases were fatal.
8% reported Grade 3 QT prolongation. Ivosidenib was reduced in one patient and held in five patients (for any grade of QT prolongation), and no cases were Grade 4 or fatal.
9.6% reported IDH-differentiation syndrome (IDH-DS), which was managed with corticosteroids and diuretics. None were Grade 4 or fatal.
Efficacy Data
Data from 125 R/R AML patients from the primary analysis set demonstrated a combined CR+CRh rate of 30.4% [95% CI 22.5, 39.3], which is the primary endpoint of the study. The CR rate was 21.6% (27 of 125 patients) [95% CI 14.7, 29.8] and the CRh rate was 8.8% (11 of 125 patients). CRh (complete remission with partial hematological recovery) is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).

Overall response rate (ORR) was 41.6% (52 of 125 patients).
Median duration of response was 9.3 months [95% CI 5.6, 18.3] for patients who achieved a CR, 8.2 months [95% CI 5.5, 12.0] for patients who achieved a CR/CRh and 6.5 months [95% CI 4.6, 9.3] for all patients who responded.
Median time to first response was 1.9 months (0.8-4.7) for all patients who responded, median time to CR was 2.8 months (0.9-8.3) for patients who achieved a CR, and median time to CR/CRh was 2.7 months (0.9-5.6) for patients who achieved a CR/CRh.
At the time of the data cut-off, median overall survival (OS) as observed in the study has not yet been reached for patients who achieved a CR/CRh. OS was 9.3 months [95% CI 3.7, 10.8] for non-CR/CRh responders, 3.9 months [95% CI 2.8, 5.8] for non-responders, and 8.8 months [95% CI 6.7, 10.2] overall.
Of the patients who were transfusion dependent at baseline and achieved a CR, 100% became independent of platelet transfusions and 84.6% became independent of red blood cell (RBC) transfusions during any 56-day post baseline period.
Of the patients who were transfusion dependent at baseline and achieved a CRh, 71.4% became independent of platelet transfusions and 75.0% became independent of RBC transfusions during any 56-day post baseline period. Transfusion independence was also seen among non-CR/CRh responders and non-responders. Non-CR/CRh responders include patients with CR with incomplete hematologic recovery (CRi), CR with incomplete platelet recovery (CRp) and morphologic leukemia-free state (MLFS) who are not CRh.
Response in Untreated AML and MDS
An efficacy analysis was also presented for 34 untreated AML patients not eligible for standard of care therapies in expansion Arm 2 and from dose escalation whose starting dose was 500 mg daily and 12 myelodysplastic syndrome (MDS) patients in expansion Arm 3 and from dose escalation whose starting dose was 500 mg daily.

Data from 34 untreated AML patients demonstrated a 55.9% ORR and a CR rate of 20.6%. The median duration of response was 9.2 months [95% CI 1.9, NE], and median duration of CR has not yet been reached.
Data from 12 MDS patients demonstrated a 91.7% ORR and a CR rate of 41.7%.
Clinical Development in AML
Ivosidenib continues to be studied in the following ongoing clinical trials in AML:

Phase 3 AGILE study evaluating the safety and efficacy of ivosidenib + azacitidine vs. placebo + azacitidine in adults with previously untreated IDH1m AML who are considered appropriate candidates for non-intensive therapy
Phase 1b study of either ivosidenib or enasidenib in combination with standard induction and consolidation chemotherapy in newly diagnosed AML
Phase 1/2 study of either ivosidenib or enasidenib in combination with azacitidine in newly diagnosed AML
Agios is on track to file a New Drug Application (NDA) for ivosidenib with the U.S. Food and Drug Administration by the end of 2017.

About the Phase 1 Trial for Ivosidenib in Advanced Hematologic Malignancies
Ivosidenib (AG-120) is being evaluated in an ongoing Phase 1 trial that includes a dose-escalation phase and four expansion arms, including:

Arm 1: IDH1 mutant positive AML patients who relapsed after bone marrow transplantation, are in second or later relapse, refractory to initial induction or reinduction treatment, or who relapse within one year of initial treatment, excluding patients with favorable-risk status
Arm 2: untreated IDH1 mutant positive AML patients who are not candidates for standard-of-care chemotherapy
Arm 3: patients with other non-AML IDH1 mutant, relapsed or refractory advanced hematologic malignancies
Arm 4: patients with relapsed IDH1 mutant positive AML not eligible for arm 1 who have failed or are unable to receive standard of care
About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to the American Cancer Society, the median age of onset is 66. The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.

Investor Event and Webcast Information
Agios will host an investor event on Monday, December 11, 2017 beginning at 8:00 p.m. ET in Atlanta to review data presented at ASH (Free ASH Whitepaper). The event will be webcast live and can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com.