Monthly Archives: June 2020

An area where stem cell biology and medicine are combining effectively is the establishment of new cell therapies. However, current therapies are limited to a narrow set of cell types that can be isolated or created and expanded in vitro. Dr Owen Rackham discusses how utilising computational approaches will further enhance applications of stem-cell-derived therapies in the future.

For decades (or perhaps centuries) the approach in cell biology has remained relatively unchanged. We isolate cells and with our confined knowledge of their endogenous conditions, begin to experiment until we can sustain them in vitro. Once established, we can conduct further investigation to assess a cells response to different conditions, changes over time or response to manipulation. This is especially true of stem cell biology, established from tireless efforts to incrementally improve culture conditions or differentiation protocols based on fragmented knowledge of developmental processes. Despite this, the promise of stem-cell therapies is already being realised in the clinic, but the breadth of cell types being used is still relatively narrow. Recent technological advances in the field have been focused on the safe and scalable manufacture of therapies. While these are revolutionary breakthroughs, the applications are largely limited to T cells, haematopoietic- and pluripotent-stem cells (HSCs and PSCs), a small fraction in the grand heterogeneity of cell types. Consequently, the lack of cell source diversity prevents cell therapy from fulfilling its clinical potential, pointing to the need for new means to isolate or generate source cells.

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Using big data approaches to develop cell therapies - Drug Target Review

Just a few months after GlaxoSmithKline penned a $50 million deal with biotech Immatics for its T-cell work, the executive running the Big Pharmas cancer cell therapy unit is upping sticks to join the U.S.-European startup.

Cedrik Britten, M.D., becomes the biotechs new chief medical officer to help run its adoptive cell therapy and T-cell receptor (TCR) bispecifics platform, which is focused on various solid tumors.

This platform has seen it pen a series of collaborations in recent years, leveraging its pool of around 200 targets to land deals with Amgen, Celgene and Genmab.

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One of the more recent partners has been GSK, Brittens former employer, where he had been vice president and head of the oncology cell therapy research unit for five years, joining the U.K. Big Pharma after serving at Germanys BioNTech.

Back in February, GSK struck a deal to access two of Immatics' TCR therapeutics, seeing it nab $50 million (46 million) upfront with $550 million in milestones for TCRs against two solid tumor targets identified by Immatics.

At the time, Immatics CEO Harpreet Singh told FierceBiotech that the way he sees it, the deals are testament to the potential for TCR therapies to expand the list of solid tumors that are amenable to treatment using immunotherapies.

The target space that we can tap into with our platforms and technologies is approximately three to four times bigger than the CAR-T space. What we can do with TCRs is tap into intracellular targets, which are not accessible to CAR-Ts and antibodies, Singh said.

Now, he has GSKs leading cell therapy exec to help push on in this space.

This change-up has caused some shuffles in the company and one exit. Carsten Reinhardt, M.D., Ph.D., the current CMO, will take on the newly created role of chief development officer to lead Immatics product development strategy.

Carsten will also continue to lead the TCR bispecifics platform and pipeline as well as the immunology and translational development functions at Immatics.

But this means there is no room for ex-Astellas exec Stephen Eck, M.D., Ph.D., who had been its CMO in Houston and will exit the biotech at the end of June but stay on for a few weeks to to support the transition. Eck left Fiercer 15 winner Aravive Biologics as its CEO in 2018 to take up the CMO role at Immatics.

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GSK's cell therapy R&D lead jumps ship to partner Immatics - FierceBiotech

Cell therapy manufacturing costs could be reduced dramatically using immobilized growth factors in culture according to research.

Industry interest in cell therapies has increased significantly in recent years. According to a report by US industry group PhRMA, there are 362 cell and gene therapies in clinical development, up from 289 in 2018.

The surge in cell therapies entering the clinic is the result of years of pioneering research by Americas biopharmaceutical research companies, according to PhRMA.

Image: iStock/Sviatlana Zyhmantovich

It also reflects the potential revenue cell therapies can generate. According to analysis by market research firm Bioinformant while prices vary, all cell therapies are expensive.

For example, cell therapies for wound care cost between $1,500 and $2,500 per administration, while those delivered via injection can cost up to $200,000 per shot. Cell-based gene therapies are valued in the $500,000 to $1 million range.

But revenue is not the only factor. The prices also reflect the high cost of goods sold (COGS) for a cell therapy according to Bioinformant.

The cost of manufacturing a cell product cannot be compared with small molecule products manufactured by pharmaceutical companies or biomolecules produced by biotechnology companies. Cell therapies are costlier to develop, with autologous cell products commanding the highest price tags.

In general, the manufacturing cost of autologous cell product is many times higher than that of an allogeneic product and this is reflected in the market pricing the authors wrote.

Growth factors as the name suggests are proteins that stimulate cell growth. They are one of the most costly components of the cell therapy manufacturing process according to a 2018 study published in Frontiers in Medicine.

The authors who looked at production strategies for allogenic therapies said Identifying mimetic-based alternatives to costly growth factors or leaner media alternatives would help to substantially reduce cost of goods.

Another approach is to immobilize growth factors used in cell culture according to the team behind a study due to be published in Frontiers in Bioengineering and Biotechnology.

Author Marion Brunck, associate professor at the Monterrey Institute of Technology and Higher Education (ITESM), told Bioprocess Insider Immobilizing growth factors is a good idea in general, as the process stabilizes the protein and prevents its degradation, internalization, i.e. bioactivity does not decrease at the same rate as with soluble proteins.

However, some growth factors must be internalized for the transduction cascade to occur appropriately, in these situations, a different approach may be sought out, for example immobilizing the growth factor by physical entrapment which allow a gradual release in culture media.

The take home message is that it may be a very good idea to decrease production cost but the biology of the growth factor (GF) and its signaling mechanistics must be well known.

Brunck added that, The impact of GF immobilization on cost will definitely vary depending on each individual process. In some cases, culture media accounts for more than half of the cost of goods, and within the cost of culture media, GF is again a big contributor.

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growth factors to cut cell therapy COGS - Bioprocess Insider - BioProcess Insider

Optimized tandem CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy induced potent and durable anti-tumor responses as treatment of patients with relapsed/refractory B cell non-Hodgkin lymphoma (B-NHL) with good control of cytokine release syndrome (CRS) and CAR T-related encephalopathy syndrome, according to a phase 1/2 clinical trial presented in a poster at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

After a median of 13.5 months of follow-up (IQR, 33.2-3.3), 84% of patients had an objective response, and 74% had a complete response (CR). The duration of overall response rate (ORR) at 6 months was 94% and 74% at 12 months.

Both the median progression-free and overall survivals had not been reached for patients at the time of data cut-off. At 6 months, the progression-free survival rate was 76%, and at 12 months, it was 59%.

Sixty-two patients experienced CRS (71%), which was grade 1 or 2 in 61% of patients and grade 3 or greater in 10%. The median time to the onset of CRS after infusion was 1 day (range, 1-5). The median duration of CRS was 6 days (range, 1-9). Investigators also noted that the median time to the onset of grade 3 CRS was 1 day (range, 1-2).

The most common adverse events within 1 month of the IV infusion were leukopenia, pyrexia, and anorexia. Only 2 patients (2%) experienced CAR T-cell-related encephalopathy syndrome of grade 3 severity.

Three treatment-related deaths occurred in the study, 2 due to pulmonary infection and 1 due to deposition of CAR T cells in pulmonary alveoli.

Ninety-nine patients were screened for the study, of which 87 received the infusion and 74 were followed for at least 3 months before the data cutoff date. Patients underwent leukapheresis and conditioning chemotherapy, which was followed by a single intravenous infusion of tandem CD19/20 CAR T cells on day 0 at a dose of 0.5x106x106 per kg of body weight.

The majority of patients in the study were under the age of 60 years (82%) and female (53%). Overall, 62% of patients had an ECOG performance status of 0 or 1 versus 38% who had a 2. Upon study entry, 85% had stage III or IV disease and 15% had stage I or II. Patients were diagnosed with either diffuse large B-cell lymphoma (66%), follicular lymphoma (15%), transformed follicular lymphoma (7%), primary mediastinal B-cell lymphoma (6%) or other (6%).

Fifty-six percent of patients had 3 to 5 prior lines of anti-neoplastic therapy, while 27% had 2 or less and 17% had 6 or more. The majority of patients had a lesion diameter less than 10 cm (78%) and had tumor burden SPD of 100 cm2 or more (55%). Eighty percent of the patients were refractory, 20% had relapsed to second-line or later therapy, 14% became refractory after stem cell transplant, and 10% had relapsed after a prior CD19 CAR-T cell therapy.

To be eligible for the study, patients had to be between the ages of 16 and 70 years, and they could not have received prior anti-CD20 monoclonal antibody and anthracycline treatment. Patients had to have an ECOG performance status of 0 to 2 with a life expectancy greater than 3 months and adequate organ function to enroll in the study. Patients also had to have measurable disease according to the IWG Response Criteria for Malignant Lymphoma.

Patients who had a CR with no evidence of disease were ineligible to enroll. If they had definite involvement of the gastrointestinal tract, negative tumor puncture detection in both CD19 and CD20, or had serious uncontrolled medical disorders or active infections, they also could not enroll. Patients were also excluded from the study if they were deemed unsuitable for the trial based on clinical judgement or were pregnant or lactating.

CD19-targeted CAR T cells have been highly effective in the treatment landscape of hematologic malignancies, but the recurrence rate appears high, which is a major obstacle to durable remissions with this therapy. This study aimed to evaluate the safety and tolerability of intravenous tandem CD19/20 CAR T cells among patients with relapsed/refractory NHL.

Secondary objectives of this study also included assessment of efficacy of the study treatment defined by ORR and evaluation of the duration of overall response, progression-free and overall survival. An exploratory objective of the study was to determine in vivo expansion and persistence of the Tandem CD19/CD20 CAR T cells.

The rationale for this study was to address the high recurrence rate observed with CAR T-cell therapy, which often prevents durable remission after treatment. Overall the optimized tandem CAR T treatment appeared feasible in patients with B-NHL. Although many of the patients in the study had heavy tumor burden, were in poor physical condition, or had highly aggressive characteristics, they were still able to achieve a satisfactory ORR and CR rate with the tandem CD19/CD20 CAR-engineered T-cell therapy.

Reference

Ja-Jing Z, Yao W, Zhi-Qiang Wu, et al. Safety and Efficacy of Optimized Tandem CD19/CD20 CAR-Engineered T Cells in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma. J Clin Oncol. 38: 2020 (suppl; abstr 3034). doi: 10.1200/JCO.2020.38.15_suppl.3034

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Optimized Tandem CAR T-Cell Therapy Targeted CD19/CD20 Appears Feasible in B-NHL - Targeted Oncology

Cell and gene therapies must scale up on an industrial level if they are to deliver their full potential to patients worldwide, according to speakers at the International Society of Cell Therapy meeting, ISCT Paris 2020 Virtual, May 29.

As the industry moves from clinical to commercial, we are reaching an inflection point and face key challenges, Alberto Santagastino, VP, head of the cell and gene technologies business unit at Lonza, said. Chief among them are improving process development and addressing the manufacturing pressures of technology, timeline, and costs. We need to look at the practicalities of how to make therapies available.

Traditional therapies experience a rapid increase in demand and then plateau. Curative cell and gene therapies, however, will have a steep adoption curve and an almost equally steep decline as the prevalence peak is treated. Afterward, only new incidences remain.

During the life of the therapy, the cost will decline, if history is to be trusted. He cited monoclonal antibodies as an example. Initially, they cost $30,000 per gram. Now they cost hundreds of dollars, or less. Cell and gene therapy developers should assume a similar curve.

When Santagastino talks about the need to industrialize, he really means mass customization rather than the type of industrialization associated with blockbuster drugs. Using a mass customization model, the industry will produce a single, customized product with the same efficacy as a standard, mass-produced product.

Embracing that model means focusing early on platforms.

A major paradigm shift must occur, he told the ISCT audience, to move cell therapy from what can be done at a clinical center to mass customization. For example, manufacturers need to think about moving to 3D bioreactor manufacturing and away from using viral vectors.

Process development is the foundation for successful therapy commercialization, Santagastino continued. He advised thinking very early about how to bring the process to the clinic. This includes determining not only which materials are best for therapeutic development, but also which are readily available in large quantities. Additionally, processes should be designed to they can be completed during one work shift. Allowing a process to extend over multiple work shifts creates difficulties, he said.

Take CAR-T therapies, for example. Autologous therapies differ batch to batch, so standardization is difficult. Developers must deal with the challenges of ensuring T-cell quality, patient health (or death while waiting for the therapy to be developed), commercial viability, scale-up, harvesting and manufacturing failures as well as supply chain issues. At the end of it all, Santagastino said, Wide batch-to-batch variability indicates youre not in control, and that distresses regulators. Lonza is addressing that challenge with an automatic, scalable, single-used system, dubbed Cocoon, for improved process control.

An alternative solution to autologous challenges is to develop allogeneic therapies. They have challenges, too, in the form of multiplex gene editing, scale-up and manufacturing, large-volume downstream processes, purification, quality and GMP tissue sourcing.

For allogeneic therapies, Lonza is addressing the donor variability issue with a pool of what it calls well-characterized super donors. Its also developing a scalable closed bioreactor system to address many but not all of the remaining issues, both upstream and down.

Whichever approach is used to develop cell therapies, Santagastino recommended taking a holistic approach that includes developing an automated quality system, addresses manufacturing variability and considers the entire supply chain.

When Novartis developed Kymriah (tisagenlecleucel), its CAR-T therapy for oncology, it took a comprehensive approach early on. With such a complex and innovative type of therapy, it understood the value of involving multiple stakeholders early on. Therefore, the company worked closely with its scientific partners, regulators, payers and the physicians in clinical trials throughout the development process, Emanuele Ostuni, Ph.D., head of cell & gene therapies Europe at Novartis Oncology, pointed out in a following presentation.

The delivery of autologous therapies is very different from traditional drug development. It creates a host of issues and a need to do things pharma hasnt done before, like providing full customer support, he said at the ISCT meeting.

Dr. Ostuni, therefore, called for a seamless, integrated approach to delivering autologous therapies, similar to the white glove services available for consumer products. This means providing full-circle customer support with live customer service in multiple languages, a secure and user-friendly web portal and a trusted chain of identity as cells are drawn from patients, shipped to manufacturers, reprogrammed and expanded, shipped to caregivers and re-infused into patients.

The global access to this autologous therapy expands the demands, but also adds value to the product. Broad global access helps ensure the value of our therapies is recognized, Dr. Ostuni explained. In launching globally, Novartis remained flexible, working with payers who each have slightly different needs and approaches to ensure the therapy was reimbursed.

From a payers perspective, cell therapy is unlike traditional drugs. Traditionally, payers collect one-year, budgetary data on a drug, but data from cell therapies should be analyzed over multiple years. Thats why some payers balk at therapies that are initially expensive but are cost-effective in the long-term.

That difference creates the need for a lot of innovation to ensure the value of the therapy is recognized and that a sustainable commercial arrangement is developed, Dr. Ostuni said. This isnt how most diseases are managed, and payers arent used to it.

Innovation must happen on multiple fronts, he emphasized. For CAR-T therapy at Novartis, this meant addressing immunogenicity by using humanized constructs, safety by ensuring early anticytokine activity, resistance by targeting the tumor microenvironment and relapse by combining two CAR-T products for better targeting.

Along the way, manufacturing had to be improved to ensure scalability for this allogeneic off-the-shelf product. Scaleup is critical, Dr. Ostuni said. We invested the effort and capital to ensure a broad manufacturing network to supply regions of the world and thus simplify logistics. We have a multi-source environment, so an emergency at one facility wont negatively affect supplies. Two European facilities are coming on line in a few months, and more will be online later.

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Why Cell and Gene Therapies Need a Paradigm Shift to Enable Commercial Scale-up - BioSpace

WASHINGTON, June 3, 2020 /PRNewswire/ --A new systematic review and meta-analysis of clinical studies using mesenchymal stromal cells (MSCs) led by a team at the Mayo Clinic, and including researchers from Emory, Duke, Case-Western, and the University of Miami, shows a trend toward improved outcomes and reduced mortality for patients with acute respiratory distress syndrome (ARDS), a major complication for patients with COVID-19. This studyand several othersalso have shown that MSCs are safe for patients.

Based on these findings, the authors call for the rapid commencement of large-scale, confirmatory clinical trials to build on the existing evidence base, which shows a trend toward improved pulmonary function and reduced severe lung inflammation for patients with ARDS, paving the way toward another treatment option for seriously ill patients with COVID-19.

To date, nearly two million Americans have tested positive for COVID-19 and more than 100,000 Americans have died. In its most severe form, COVID-19 leads to ARDSa life-threatening lung injury that allows fluid to leak into the lungs and makes it difficult for patients to breathe. More than 40 percent of individuals hospitalized for severe and critical COVID-19 develop ARDS, and 22 percent to 62 percent of those who are diagnosed and become critically ill, die from the disease. There is no effective treatment for ARDS today; MSCs potentially offer a unique therapeutic option to help patients in need.

"The analysis shows a positive trend in outcomes when treating ARDS patients with MSC therapy and represents the potential to save thousands of patients with COVID-19 induced ARDS," said Wenchun Qu, MD, PhD of the Mayo Clinic and first author of the paper. "The potential benefitcombined with the demonstrated safety of these therapiessupports the need for rapid commencement of more clinical trials."

"Acute respiratory distress syndrome is a rapidly progressive disease that can occur in critically ill patients," said Anthony Atala, MD, Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "Having additional potential therapies, such as MSCs, could be highly beneficial to patients with COVID-19."

To date, the FDA has approved more than a dozen investigational new drug applications for the use of MSCs for COVID-19-related conditions. The National Institutes of Health (NIH) has also supported the use of MSCs and other regenerative cell therapies to help patients with other conditions. The bipartisan 21st Century Cures Act provided $30 million in funding to the NIH over three years for clinical research for such therapies. However, these limited investments expire in fiscal year 2020.

The Alliance for Cell Therapy Now and the Regenerative Medicine Foundation support the recommendation of the authors, who urge funding for larger studies that build on the results to date. Collaboration and funding are also needed to collect and analyze the evidence from multiple ongoing and new studies, to better evaluate outcomes and potential benefits of MSC therapy for COVID-19 patients in need. A portion of the more than $10 billion in funding directed by Congress to the Biomedical Advanced Research and Development Authority (BARDA) and the NIH for COVID-19 should be used to support these goals.

About the Alliance for Cell Therapy Now

Alliance for Cell Therapy Now (ACT Now) is an independent, non-profit organization devoted to advancing the availability of and access to safe and effective cell therapies for patients in need. ACT Now convenes experts and stakeholders to develop and advance sound policies that will improve the development, manufacturing, delivery, and improvement of regenerative cell therapies. See http://allianceforcelltherapynow.org/

About the Regenerative Medicine Foundation

The non-profit Regenerative Medicine Foundation (RMF) fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF pursues its mission by producing its flagship World Stem Cell Summit, honoring leaders through the Stem Cell and Regenerative Medicine Action Awards, and promoting educational initiatives. STEM CELLS Translational Medicine is RMF's official journal partner. See https://www.regmedfoundation.org/

SOURCE Alliance for Cell Therapy Now

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MSC Therapy for Acute Respiratory Distress Syndrome; It's Time to Accelerate Clinical Trials for COVID-19 Patients in Need - PRNewswire

GC027,the first humanized chimeric antigen receptor (CAR)-T cell therapy for relapsed/refractoryT-cell acute lymphoblastic leukemia (T-ALL) in adults, appears to be botheffective and have a manageable safety profile, according to research presentedduring the ASCO20 Virtual Scientific Program.

Mortalityrates are high in relapsed/refractory T-ALL, necessitating novel treatments toimprove survival. CD7, a T-cell antigen expressed in more than 95% of diseasesamples, represents a plausible target in this setting. GC027, which targetsCD7 and was developed using using lentivirus and CRISPR/Cas9, showed promise inmurine models for treating T-ALL.

For this single-arm, open-label study, researchers evaluated the safety and efficacy of GC027 in relapsed/refractory T-ALL. All included patients were between 18 and 70 years old, had a projected survival of more than 3 months, and had a performance status of 0 to 2. Patients with extramedullary disease or central nervous system involvement were not eligible to participate.

Fivemen (median age, 24 years) were enrolled in the trial. The median number ofprior lines of therapy was 5, no patients had undergone prior stem celltransplantation, and the median baseline bone marrow tumor burden was 38.2%.

All5 patients had a complete response or complete response with incomplete hematologicrecovery, and 4 of the 5 patients were minimal residual diseasenegative.

Allpatients also experienced grade 3 (4 patients) or 4 (1 patients) cytokinerelease syndrome; no grade 5 events of any kind were reported.

Witha single infusion of GC027, 80% of the patients had robust CAR-T cell expansionand achieved persistent [minimal residual diseasenegative complete response]without using any biologics as part of the preconditioning therapy or bridgingto [hematopoietic stem cell transplantation], the authors wrote.

Wang X, Li S, Gao L, et al. Safety and efficacy results of GC027: The first-in-human, universal CAR-T cell therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl): abstr 3013.

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GC027 Shows Promise as Therapy for Adult Relapsed, Refractory T-Cell ALL - Hematology Advisor

ALLO-501, an allogeneic CAR T-cell therapy, paired with ALLO-647, a monoclonal antibody, yielded high response rates and a manageable safety profile in patients with relapsed/refractory diffuse large B-cell or follicular lymphoma, according to a first-in-human study presented at the 2020 ASCO Virtual Scientific Program.

The 2 treatments were used sequentially in the open-label, phase I ALPHA study that occurred at 6 U.S. sites, demonstrating an overall response rate (ORR) of 63%, including a 37% complete response rate in 19 evaluable, previously treated adults.

Researchers believe that allogeneic CAR T therapy, made from healthy donor T cells, can provide the benefits of autologous CAR T therapy while increasing patient access, the studys lead author, Sattva S. Neelapu, MD, of The University of Texas MD Anderson Cancer Center in Houston, explained. He added that providing an off-the-shelf version of CAR T-cell therapy makes it available to patients more quickly, including on occasions when repeat dosing is necessary.

ALL0-501 is a genetically modified anti-CD19 CAR T-cell product in which the protein TCR alpha is disrupted to reduce the risk of graft-versus-host disease (GvHD). To support the effectiveness of the 2-pronged approach, the protein CD52 has been knocked out in ALLO-501 so that its partner therapy, the anti-CD52 monoclonal antibody ALLO-647, can be used successfully in lymphodepletion.

ALPHAs primary endpoint was the safety and dose-limiting toxicity of ALL0-647 followed by ALLO-501. A secondary endpoint was ORR.

Eligible participants had advanced disease, an ECOG status of 0 or 1 and had been treated with at least 2 previous lines of therapy. Prior treatment with an anti-CD20 monoclonal antibody or with autologous CAR T therapy was permitted, as long as the patients tumor remained CD19-positive.

A total of 22 patients, whose median age was 63 years, were treated. Approximately two-thirds had diffuse large B-cell lymphoma and the rest had follicular lymphoma. Approximately half had high-risk disease. Their median number of previous treatments was 4.

Patients underwent lymphodepletion that included fludarabine, cyclophosphamide and ALLO-647; 3 regimens of varying doses were tested, which included ALLO-647 doses of 39 mg and 90 mg. This was followed by infusion of ALLO-501 at CAR-T cell doses of 40 million, 120 million, or 360 million, Neelapu said.

All the medication in the trial was made from the T cells of a single healthy donor, he said.

At a median follow-up of 3.8 months, 63% of patients (n = 12) demonstrated a response to treatment (95% CI, 38%-84%), including 37% (n = 7) who had complete responses (95% CI, 16%-62%). Most patients experienced tumor shrinkage, Neelapu said. The median time until response was 1 month, and 9 patients continue to respond. One patient achieved a complete response after a second infusion of ALLO-501, Neelapu reported.

He noted that 10 of 16 patients evaluated to date showed evidence of CAR-T cell expansion, which was associated with better response.

No dose-limiting toxicity or GvHD was observed in any of the patients treated. The most common adverse events of grade 3 or higher were neutropenia (55.6%), leukopenia (33.3%), and anemia (22.2%). Seven patients developed cytokine release syndrome, 2 of them at grade 1, 4 at grade 2 and 1 at grade 3, all reversible without steroids or tocilizumab (Actemra), according to the researchers. About half the patients had infusion reactions, most grade 2 or lower. Eleven infections reported were grade 3 and lower, mostly asymptomatic and diagnosed during weekly monitoring, Neelapu said. Finally, 1 patient developed a grade 1 neurotoxicity that resolved without treatment.

Neelapu said the safety of the 2 drugs appears comparable to that of autologous CAR T products currently approved for use.

Researchers noted that higher doses of ALLO-647 could have a potential association with deeper responses, as a larger proportion of patients on the greater dose saw a complete response. Follow-up is ongoing as researchers seek to enroll more patients to test for further response.

Reference:

Neelapu SS, Munoz J, Locke FL, et. al. First-in-human data of ALLO-501 and ALLO-647 in relapsed/refractory large B-cell or follicular lymphoma: ALPHA study. Presented at: 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 8002.

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Off-the-Shelf CAR T-Cell Therapy Shows Promise in Relapsed/Refractory B-Cell Lymphomas - Cancer Network