On February 25, 2019 EORTC reported that resulted phase II 62043 and phase III 62072 published in Clinical Cancer Research, showed that in patients with soft tissue sarcoma, the concomitant use of gastric acid suppressant (GAS) therapy and the anticancer therapeutic pazopanib was associated with significantly reduced progression-free survival and overall survival.

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It is estimated that up to 50 percent of those undergoing cancer treatment utilize Gastric Acid Suppressant (GAS) therapy. Common GAS drugs include proton pump inhibitors, such as omeprazole and esomeprazole magnesium, or histamine H2-receptor blockers, such as ranitidine.

The absorption of pazopanib, a multi-kinase inhibitor used in the treatment of renal cell carcinoma and soft tissue sarcoma, is pH-dependent, noted Mir. "We know that pazopanib tablets taken orally need to go into an acidic environment, namely the stomach, in order to dissolve," he explained. "As the primary function of GAS therapy is to reduce the acidity in the stomach, these drugs can reduce the absorption of pazopanib," Mir continued.

Previous work has shown that GAS therapy reduced the absorption of pazopanib as measured in plasma in patients with solid tumors, noted Mir. "We wanted to determine if the use of GAS drugs had an effect on survival outcomes in sarcoma patients taking pazopanib," he said.

Mir and colleagues analyzed data from the completed EORTC phase II 62043 and phase III 62072 clinical trials of patients with advanced soft-tissue sarcoma treated with pazopanib. The researchers first compared the outcome of patients treated with pazopanib with or without gastric acid suppressive agents for ≥ 80% of treatment duration, and subsequently using various thresholds. 333 patients treated with pazopanib were eligible for analysis; of these, 117 (35.1 percent) received GAS drugs at least once during pazopanib treatment, 59 (17.7 percent) utilized GAS therapy concomitantly for more than 80 percent of pazopanib treatment duration, and 19 (5.7 percent) were already utilizing GAS drugs at the time of trial registration.

Following multivariable analysis, compared to patients who did not use GAS therapy during pazopanib treatment, those who concomitantly utilized GAS for at least 80 percent of treatment duration had significantly reduced progression-free survival (median of 4.6 months compared to 2.8 months, respectively). Concomitant use of GAS also significantly reduced overall survival; those who utilized GAS therapy for at least 80 percent of treatment duration had shorter median overall survival (8 months) compared to those who did not use GAS therapy (12.6 months).

Among the 110 placebo-treated patients from the phase III trial who were eligible for analysis, there were no associations between concomitant GAS use and progression-free survival or overall survival. "This suggests that the drug-drug interaction between GAS and pazopanib directly affected the survival outcomes of sarcoma patients," Mir said.

Mir and colleagues also found that GAS therapy did not reduce the frequency of pazopanib-related toxicities. "I think that our results are practice-changing, and I would discourage oncologists against prescribing gastric acid suppressants when patients are treated with pazopanib, unless it is the only option for the patient," Mir said.

"Patients often utilize GAS therapy for abdominal pain, which is not always related to stomach acidity," said Mir. "I would predict that the majority of patients taking GAS drugs could utilize a different therapy to aid in their abdominal discomfort. Moreover, it is important for patients to inform their oncologists of all the medications that they are taking during cancer so that potential drug-drug interactions can be identified and avoided."

Limitations of this research include its retrospective nature. The analysis was based on the reported use of GAS therapy in the course of the trial, a relatively small sample size and a lack of pharmacokinetic data, which are not routinely collected in late-phase trials.

This study was sponsored by Fonds Cancer (FOCA) from Belgium.

On February 25, 2019 Hummingbird Bioscience reported it has been awarded a product development grant totalling $13.1 million from the Cancer Prevention and Research Institute of Texas (CPRIT) (Press release, Hummingbird Bioscience, FEB 25, 2019, View Source [SID1234554020]).

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The grant will support the Phase IA/B clinical trials of the company’s first-in-class anti-VISTA therapeutic antibody for the treatment of VISTA mediated suppression of anti-tumor immunity in solid tumors and lymphomas that are unresponsive to existing therapies. Hummingbird Bioscience is a systems-biology enabled biotech company focused on the discovery and development of novel cancer therapeutics.

The CPRIT review for this grant included an in-depth evaluation of HMBD-002, an antibody that uniquely neutralizes VISTA function, by a panel of scientific, medical, and industry experts. The evaluation included rigorous review of the pre-clinical data, as well as regulatory, research and development, and intellectual property due diligence.

The grant will support the Phase IA/B clinical study and preparatory steps including GMP manufacturing and Investigational New Drug (IND) submission for the HMBD-002 program. The grant will also support the relocation of the company’s U.S. headquarters to Texas. Clinical trials for HMBD-002 are anticipated to begin in 2020. Hummingbird Bioscience was the only successful application of its type for this grant cycle.

The award follows the recent announcement of Nobel Laureate James P. Allison, Ph.D. and Padmanee Sharma, M.D., Ph.D. joining Hummingbird’s Scientific Advisory Board.

"We are delighted to be awarded this highly-selective grant from CPRIT and to start building our operations in Texas," said Piers Ingram, Ph.D., CEO of Hummingbird Bioscience. "Our company applies systems biology approaches to generate uniquely differentiated therapeutic antibodies. We are thrilled CPRIT’s panel of experts agrees that developing this anti-VISTA immuno-oncology program has the potential to significantly benefit patients."

On February 25, 2019 Marker Therapeutics, Inc. (NASDAQ:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported updated data from four clinical trials using the Company’s multi-antigen targeted T cell (MultiTAA) therapies (Press release, Marker Therapeutics, FEB 25, 2019, View Source;utm_medium=email&utm_campaign=investor_alerts&utm_content=Marker+Therapeutics+Announces+Clinical+Update+at+the+Transplantation+%26+Cellular+Therapy+Meetings+of+ASBMT+and+CIBMTR+2019 [SID1234533634]). The data was reviewed in oral and poster presentations at the Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR 2019 which took place in Houston, TX from February 20-24. Among the highlights, were results from an ongoing study including patients with acute myeloid leukemia (AML), which were reviewed in an oral presentation by Dr. Premal Lulla, M.B.B.S., Assistant Professor of Medicine, Baylor College of Medicine.

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"We continue to be highly encouraged by the clinical results we’ve seen to date with our MultiTAA therapies. In AML, we believe we are seeing increasing evidence of meaningful therapeutic benefit for patients with limited treatment alternatives. Our MultiTAA therapy appears to be safe and well-tolerated with the potential to mediate a meaningful anti-tumor effect, in addition to demonstrating a compelling correlation between therapeutic responses, with superior in vivo expansion of our T cells," said Peter L. Hoang, President & CEO of Marker Therapeutics. "Similarly, the studies ongoing in acute lymphoblastic leukemia, or ALL, lymphoma and multiple myeloma continue to demonstrate positive results, and are supportive of the data we presented at ASH (Free ASH Whitepaper) in December, importantly with no additional disease relapses. Overall, this data update and our update at ASH (Free ASH Whitepaper) 2018 in December collectively have increased our total reported number of patients to 78 as compared to the 57 patients we had reported as of November."

AML Study Results

In Arm A of the AML study, 13 patients at Baylor College of Medicine were dosed with MultiTAA T cells as a maintenance therapy after receiving allogeneic stem cell transplant. Results demonstrated:

11 out of 13 patients remain alive, ranging from 6 weeks to 2.5 years post-infusion. Nine of these patients have never relapsed after MultiTAA therapy and continue to remain in complete remission (CR), durable between 6 weeks to 2.5 years;
Two patients saw local relapse in the central nervous system, but in both cases these patients were successfully treated with local therapy alone;
One patient saw extramedullary relapse and was subsequently treated in the active disease arm (Arm B) of the trial, generating a CR that was durable for 13 months; and
One patient relapsed 8 months after receiving MultiTAA T cells but following a second allogeneic stem cell transplant this patient remains alive in relapse 1.5 years following his initial T cell infusion.
In Arm B of the AML study, 6 patients suffering from active disease with relapsed/refractory (r/r) AML have been treated, with 1 patient having been treated twice for active disease with MultiTAA T cells;

2 patients were non-responsive to MultiTAA therapy and progressed with r/r disease;
1 patient developed a complete response (CR), which was durable for 13 months; and
1 patient developed a partial response (PR) that enabled that patient to receive a second allogeneic stem cell transplant;
The patient who developed a partial response saw significant tumor debulking, with circulating blasts reduced from over 50% to 15%.
2 additional patients who did not meet partial response criteria experienced disease stabilization enabling a 2-month delay to next-line therapy
Of these patients with disease stability, one patient was sufficiently stabilized to enable that patient to receive a second allogeneic stem cell transplant. The second transplant eliminated the patient’s MultiTAA T cells. This patient was given a second dose of MultiTAA T cells after initial disease relapse after the second transplant, but progressed to another line of therapy prior to any evaluable response assessment to the subsequent dose of MultiTAA T cells;
The other patient who had disease stability saw significant reduction in tumor burden, with a reduction in circulating blasts from 70% prior to infusion of MultiTAA T cells, to approximately 45% circulating blasts after MultiTAA therapy.
For patients in Arm B, overall survival ranged from 4 to 21 months after T cell infusions.
ALL Results

In addition to data from ongoing lymphoma and multiple myeloma trials, also presented in an oral presentation at the meeting were updated results from an ongoing study in ALL. Updates from this trial included:

Patients are now up to 28 months in CCR (Continued Complete Remission);
The only patient who has experienced relapse was a patient who displayed mixed donor/recipient chimerism after transplant, but remained in CCR for 6 months prior to relapse;
Patients that remain in CCR have been durable for between 4 to 28 months, with a median duration of 16 months.
"We are very excited about the results we are seeing in our early clinical trials. For patients with r/r AML, we believe that MultiTAA therapies may produce meaningful improvements in overall survival of patients who historically have had a dire prognostic outlook," stated Mythili Koneru, Senior Vice President of Clinical Development at Marker Therapeutics. "In adjuvant settings for patients currently in remission, I believe our early clinical results suggest that we may be providing significant additional protection against relapse and disease recurrence."

On February 25, 2019 Cellaria, LLC, a scientific innovator that develops revolutionary new models for cancer and other diseases, reported a new distribution partnership with Rockland Immunochemicals, Inc. (Rockland), a life science supplier and manufacturer that specializes in antibodies and antibody-based tools for research applications and assay development (Press release, Rockland, FEB 25, 2019, View Source [SID1234553932]). The agreement gives Rockland the rights to market and sell Cellaria’s high-quality next generation in-vitro disease models and cell culture media worldwide.

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With Rockland, Cellaria adds to its growing list of strategic distribution partners, expanding its global market presence and reach. Cellaria’s novel cell culture media and cancer cell models add to Rockland’s arsenal of products targeting cancer research and drug screening.

Cellaria’s cell models express different biomarkers that are directly correlated to the patient specimens used to create the models. The diversity of biomarker expression within similar categories of patients enables researchers to generate drug response and disease progression data that is highly relevant to those individual patients.

"We allow drug and cancer researchers to make much more informed decisions about which populations of patients are more likely to respond effectively to drugs that are under investigation," said David Deems, CEO of Cellaria. "Rockland’s scientific knowledge and their ability to sell cutting-edge and custom products make them a great fit to represent the innovation that we bring to market."

James Fendrick, CEO of Rockland stated, "Cellaria’s offerings will nicely complement Rockland’s existing line of cell culture products including human melanoma cell lines, fetal bovine serum, lysates and collagens. We are honored that Cellaria chose Rockland to serve as their distribution partner."

On February 23, 2019 Gamida Cell Ltd. (Nasdaq: GMDA), a leading cellular and immune therapeutics company, reported that translational data from the completed Phase 1/2 clinical study of NiCord were reported in an oral presentation at the 2019 Transplantation & Cellular Therapy (TCT) Meetings of American Society for Blood and Marrow Transplantation (ASBMT) and Center for International Blood and Marrow Transplant Research (CIBMTR) in Houston, Texas (Press release, Gamida Cell, FEB 23, 2019, View Source [SID1234533609]). The data demonstrated that treatment with NiCord, an investigational advanced cell therapy designed to enhance and expand the life-saving benefits of bone marrow transplant for patients with hematologic malignancies, resulted in rapid and robust immune reconstitution. NiCord is currently being evaluated in an international, randomized Phase 3 study in patients with hematologic malignancies.1

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"Reconstitution of a patient’s bone marrow and immune system is a crucial factor in recovery following allogeneic hematopoietic stem cell transplant," said Jaap-Jan Boelens, M.D., Ph.D., Chief, Pediatric Stem Cell Transplantation and Cellular Therapies Service, Memorial Sloan Kettering Cancer Center. "We were particularly encouraged by the finding that reconstitution of CD4+ T cells with NiCord treatment was at least as fast as transplant with unmanipulated cord blood and unrelated bone marrow in adolescents and young adults, who typically achieve more rapid recovery than adults."

Despite the curative potential of bone marrow transplants, it is estimated that more than 40 percent of eligible patients in the U.S. do not receive one for various reasons, including finding a matched donor.2 Even for patients who do receive a transplant, treatment is not always effective and can lead to serious complications that can dramatically affect quality of life.3 NiCord is intended to address the current limitations of bone marrow transplant by providing a therapeutic dose of cells while preserving the cells’ functional therapeutic characteristics.

Data Presented at TCT Annual Meeting

The oral presentation, "Rapid and Robust CD4+ and CD8+ T-, NK-, B-Cell, Dendritic Cell, and Monocyte Reconstitution after Nicotinamide-Expanded Cord Blood Transplantation" (Abstract 69), described in-depth immune reconstitution data from the completed Phase 1/2, multi-center clinical study of NiCord as a stand-alone graft after myeloablative therapy in patients with high-risk hematologic malignancies.4 Immune reconstitution for 27 patients receiving NiCord was compared to retrospective cohorts of adolescent and young adults with hematologic malignancies receiving unmanipulated cord blood transplantation (unCBT, n=27) or unrelated bone marrow transplantation (BMT, n=20). The primary endpoint was the probability of achieving CD4+ immune reconstitution (>50×106/L) within the first 100 days. Secondary endpoints included the recovery of B cells, CD4+ T cells and natural killer (NK) cells during the first year after transplantation. Analyses were performed at the University Medical Centre Utrecht, Laboratory of Translational Immunology.

The analysis showed that 91 percent of patients receiving NiCord achieved successful immune reconstitution of CD4+ T cells at 100 days after transplantation. Reconstitution of T cells in the NiCord group (median age 41.5 years) was similar to the unCBT and BMT cohorts (median age 15.4 and 14.3 years, respectively), despite the younger age of the cohorts, who would be expected to reconstitute faster. In addition, reconstitution of a number of cell types, including B cells (p = 0.02) and NK cells (p < 0.001), was significantly faster after transplantation with NiCord compared to the cohorts, and suggests that NiCord reconstitutes diverse functions of the immune system. These findings may be explained by the higher stem cell dose and proliferative capacity of NiCord.

"Our goal is to bring a potentially transformative new treatment option to patients in need of bone marrow transplant, and these data further reinforce our belief in the clinical potential of NiCord," stated Ronit Simantov, M.D., chief medical officer at Gamida Cell. "We are continuing to enroll patients in our ongoing Phase 3 study and expect to complete patient enrollment in the second half of 2019, followed by an anticipated topline data readout in the first half of 2020."

During the TCT Annual Meeting, new data were also presented from Gamida Cell’s NAM-NK clinical program, as well as initial data from a Phase 1/2 study of NiCord in patients with severe aplastic anemia. More information on those presentations can be found here.

About NiCord

NiCord, the company’s lead clinical program, is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with hematologic malignancies (blood cancers). NiCord is the first bone marrow transplant product to receive Breakthrough Therapy Designation from the U.S. Food and Drug Administration and has also received Orphan Drug Designation in the U.S. and EU. In a Phase 1/2 clinical study, NiCord demonstrated rapid and durable time to engraftment and was generally well-tolerated.5 A Phase 3 study evaluating NiCord in patients with leukemia and lymphoma is ongoing in the U.S., Europe and Asia.1 NiCord is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia.6 The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as NiCord. For more information on clinical trials of NiCord, please visit www.clinicaltrials.gov.

NAM-NK and NiCord are investigational therapies, and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.