A Phase I Open Label Clinical Trial Evaluating the Safety and Anti-Tumor Activity of Autologous T Cells Expressing Enhanced TCRs Specific for Alpha Fetoprotein (AFPᶜ³³²T) in HLA-A2 Positive Subjects With Advanced Hepatocellular Carcinoma (HCC) or Other AFP Expressing Tumor Types

This first time in human study is intended for men and women between 18 and 75 years of age who have advanced liver cancer which has grown or returned after being treated or another AFP expressing tumor. Those who did not tolerate or refused other therapies may also participate. The purpose of this study is to test the safety of genetically changed T cells that target alpha-fetoprotein (AFP) and find out what effects, if any, they have in subjects with liver cancer or other AFP expressing tumor types. This study is for subjects who have a blood test positive for appropriate HLA-A*02 P Group and have adequate AFP protein in blood or tumor, and whose noncancerous liver tissue has very little AFP protein (Liver only).
The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells.
The manufacturing of T cells takes about 1 month to complete. The T cells will be given back to the subject through an intravenous infusion after 3 days of chemotherapy. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose.
Subjects will be hospitalized for at least 1 week after receiving their T cells back and then seen frequently by the Study Physician for the next 6 months. After that, subjects will be seen every three months. If subjects have disease progression or withdraw from the study, they will then be entered into a long-term follow up for safety monitoring. In long-term follow up, subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion and annually for the next 10 years.

Start Date08 May 2017

Sponsor / Collaborator

Adaptimmune Ltd.

NCT01350401 / TerminatedPhase 1/2

Phase I/II Study to Assess the Safety and Activity of Enhanced TCR Transduced Autologous T Cells in Metastatic Melanoma

The purpose of this early (phase I/II) clinical trial is to assess the effects (both good and bad) of genetically modified T cells after chemotherapy on your cancer and general health.

Start Date01 Jun 2011

Sponsor / Collaborator

Adaptimmune Ltd.

100 Clinical Results associated with Alpha fetoprotein targeted T-cell therapy(Adaptimmune Ltd.)

100 Translational Medicine associated with Alpha fetoprotein targeted T-cell therapy(Adaptimmune Ltd.)

100 Patents (Medical) associated with Alpha fetoprotein targeted T-cell therapy(Adaptimmune Ltd.)

Literatures (Medical) associated with Alpha fetoprotein targeted T-cell therapy(Adaptimmune Ltd.)

01 Sep 2024·Oncology and Therapy

From Triple- to Penta-Exposed Multiple Myeloma: A Real-World Study in a Medicare Population

Article

Author: Delea, Thomas E ; Rodriguez Lorenc, Karen ; Ma, Qiufei ; Kroog, Glenn S ; Moynahan, Aaron ; Song, Xue ; Ge, Wenzhen ; Sabater Anaya, Natalia

INTRODUCTION:

Treatment of multiple myeloma (MM) has been transformed by novel therapies, including CD38 monoclonal antibodies (mAbs), immunomodulatory drugs (IMiDs), and proteasome inhibitors (PIs), resulting in increasing numbers of patients who are triple-class exposed (TCE; exposed to ≥ 1 drug in each class). Many patients are penta-exposed (PE; ≥ 2 IMiDs, ≥ 2 PIs, and a CD38 mAb), some are triple-class refractory (TCR), and some are PE and TCR (PE-TCR). Data on real-world outcomes in elderly patients with MM across this spectrum of exposure are limited.

METHODS:

Data from the Medicare Chronic Conditions Warehouse Database from November 2006-December 2020 were used to examine cohorts of TCE, TCR, PE, and PE-TCR patients. Outcomes were assessed from the start of the index line of therapy (LOT), defined as the first LOT after becoming TCE or PE.

RESULTS:

A total of 2830 TCE, 1371 TCR, 1121 PE, and 774 PE-TCR patients were identified. Pomalidomide was the most frequently used medication for the index LOT in all cohorts (32.6% [PE-TCR] to 43.3% [TCR]). The most frequently used regimens for the index LOT were pomalidomide plus daratumumab for TCE (17.2%) and PE (7.0%), pomalidomide plus carfilzomib for TCR (10.3%), and pomalidomide plus elotuzumab for PE-TCR (7.4%). Median time to discontinuation (TTD) ranged from 4.2 (PE-TCR) to 6.9 (TCE) months, and overall survival (OS) ranged from 13.0 (TCR) to 15.9 (PE) months. Healthcare resource utilization (HRU) was lowest for TCE and highest for PE-TCR patients. Mean monthly healthcare costs (HCC) ranged from $23,091 (TCE) to $24,412 (PE-TCR). MM medications represented 66.2% (PE-TCR) to 72.8% (TCE) of costs.

CONCLUSIONS:

In this study across a spectrum of Medicare TCE patients, there was heterogeneity in treatment regimens, suggesting no standard of care. TTD and OS were short, and HRU and HCC were high. These results underscore the potential for new therapies in this population.

01 Feb 2024·Pediatric transplantation

Comparison of tacrolimus vs. cyclosporine in pediatric hematopoietic stem cell transplantation for thalassemia

Article

Author: Yesilipek, Akif ; Uygun, Vedat ; Karaman, Irem ; Karasu, Gulsun ; Yalcin, Koray ; Daloglu, Hayriye ; Celen, Safiye Suna ; Ozturkmen, Seda ; Zhumatayev, Suleimen

Abstract:

Objectives:

Graft‐versus‐host disease (GvHD) is one of the leading causes of morbidity and mortality in patients undergoing allogeneic HSCT, and effective prevention of GvHD is critical for the success of the HSCT procedure. Calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. In this study, the efficacy and safety of Cyclosporine A (CsA) and tacrolimus (TCR) were compared in pediatric HSCT for thalassemia.

Materials and Methods:

This is a retrospective analysis of 129 pediatric patients who underwent HSCT with the diagnosis of thalassemia at Medicalpark Göztepe and Antalya Hospitals between January 2017 and December 2020.

Results:

Despite the GvHD prophylaxis, grade II–IV acute GvHD developed in 29 patients. Of these patients, 12 had only gut, 10 had only skin, 6 had combined gut and skin, and one had only liver GvHD. Fifteen of these 29 patients were in the CsA group, and 14 of them were in the TCR group. There was no significant difference between the groups in terms of acute GvHD occurrence, GvHD stage, or involvement sites. In terms of CNI‐related toxicity, neurotoxicity in 15 (CsA n = 9, TCR n = 6) and nephrotoxicity in 18 (CsA n = 4, TCR n = 14) patients were observed. While there was no difference between the two groups in terms of neurotoxicity, more nephrotoxicity developed in patients using TCR (p = .013). There was no significant difference between the groups in terms of engraftment syndrome, veno‐occlusive disease, CMV reactivation, PRES, or graft rejection.

Conclusion:

Regarding GvHD, there was no difference in efficacy between TCR and CsA usage. Patients taking TCR experienced noticeably higher nephrotoxicity in terms of adverse effects. This difference should be considered according to the patient's clinical situation while choosing a CNI.

04 Jan 2024·Journal of AOAC International

Development and Validation of Novel Quality Evaluation Methods to Differentiate Two Closely Related Species of Tinospora: A Rapid HPTLC- and HPLC-Based Assessment with MS/MS Characterization

Article

Author: Balasubramaniam, Arun Kumar ; Ghule, Chetana ; Hingorani, Lal ; Girme, Aboli ; Mulay, Vallabh ; Saste, Ganesh

Abstract:

Background:

The sympatric occurrence of the species that often resulted in different gatherings of plant material, ambiguous history on traditional use, and taxonomic flux due to similarities within the Tinospora (Menispermaceae) taxa are some of the reasons that triggered the necessity to develop robust analytical methods for efficient QC, especially to recognize dry and powder forms.

Objective:

To develop novel HPTLC-based fingerprinting of two closely resembling Tinospora species followed by HPTLC–MS analysis and identification of compounds differentiating Tinospora crispa (TCP) and Tinospora cordifolia (TCR) and a rapid and quantitative assessment by HPLC with a photodiode array detector (HPLC–PDA) with MS/MS characterization of specific TCP and TCR analytical markers.

Methods:

An HPTLC-based method was developed using chloroform–toluene–methanol–formic acid (7 + 4 + 2 + 0.2, by volume). The TCP compounds could be distinguished and isolated using successive column chromatography with complete characterization. Further these used in the reverse phase (RP)-HPLC–PDA coupled with LC–ESI (electrospray ionization)-MS/MS to quantify and confirmation in TCP and TCR.

Results:

The fingerprinting showed distinct bands in TCP stems, confirmed as clerodane- furanoditerpenoids with indirect profiling by the HPTLC–MS technique. Systematic isolation confirmed these compounds as borapetosides B and E. Thus, the RP-HPLC–PDA method was developed for these borapetosides B and E, with tinosporide to differentiate these two species. The quantitation method was well validated with good linearity (r2 >0.99) with sensitive LOD (0.49–3.71 mcg/mL) and LOQ (1.48–11.23 mcg/mL) with recoveries of 92.34–96.19%.

Conclusion:

A novel, validated HPLC–PDA method showed good resolution and reliability (up to 1% adulteration) in quantification for targeted major analytical markers from TCP to differentiate TCR. Thus, HPTLC and HPLC–PDA-based techniques are helpful with MS/MS-based characterization to identify and quantify these analytical markers from TCP (borapetoside B and E) and TCR (tinosporide) in dry and powder form.

Highlights:

This article reports on the systemic use of HPTLC–MS for separating and identifying analytical markers in Tinospora species, distinguishing TCR and TCP with quantitative HPLC–PDA and MS/MS assessment.

News (Medical) associated with Alpha fetoprotein targeted T-cell therapy(Adaptimmune Ltd.)

13 Sep 2021

·www.globenewswire.com

Adaptimmune Announces Clinical Responses across Five Solid

- Confirmed complete response in ovarian cancer, and confirmed partial responses in ovarian, head and neck, esophagogastric junction, bladder, and synovial sarcoma cancers - - Majority of patients experienced antitumor activity with a disease control rate of 86% - - ADP-A2M4CD8 cell therapy shows improved tumor cell killing and engagement of the broader immune system to fight cancer - PHILADELPHIA and OXFORD, U.K., Sept. 13, 2021 (GLOBE NEWSWIRE) -- Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in cell therapy to treat cancer, announced updated data from its Phase 1 SURPASS trial in multiple solid tumors to be presented in a digital poster at the upcoming European Society for Medical Oncology (ESMO) annual meeting. The poster will be displayed on the ESMO congress web site on Thursday, September 16th. The Company has also released a video of Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer (CEO), and Elliot Norry, Adaptimmune’s Chief Medical Officer, describing these data in more detail that can be accessed here: . “It is no longer a question of whether our SPEAR T-cells are effective against a range of MAGE-A4 expressing tumors — they undoubtedly are. Now, our focus is on turning them into approved therapies. This begins with ongoing recruitment in this SURPASS trial for people with lung, bladder, gastroesophageal, head and neck, and now ovarian cancer, and continues with the recently initiated SURPASS 2 trial in esophageal and EGJ cancers,” said Adrian Rawcliffe, Adaptimmune’s CEO. “These data bring us closer to identifying further indications to take into late-stage development and confirm our expertise in developing and enhancing cell therapies. ADP-A2M4CD8 does exactly what we designed it to do — kill cancer cells and more effectively engage the broader immune system to deliver improved potency and clinical benefit.” Dr. David Hong, Professor, Deputy Chairman in the Department of Investigational Cancer Therapeutics (Phase I Program) at The University of Texas MD Anderson Cancer Center said, “We are encouraged by these promising early data from the SURPASS trial. Having previously seen strong responses with afami-cel, this next-generation cell therapy appears safe and demonstrated antitumor activity for a majority of patients across many cancer indications.” Topline results from the Phase 1 SURPASS trial (data cut-off August 2, 2021)Emerging efficacy and durability data are promising with responses in five solid tumor indications * Of 25 patients who received ADP-A2M4CD8, 3 were not evaluable at the time of data cut-off: 2 patients (ovarian or esophageal cancers) did not have post-baseline scans; 1 patient (EGJ) had a post-baseline scan that did not meet the ≥4-week duration for evaluation of stable disease** One PR in head and neck cancer and one PR in EGJ cancer were reported previously at SITC 2020 ADP-A2M4CD8 demonstrated an acceptable safety profile ADP-A2M4CD8 was designed to be more potent than the first-generation product Initial translational data confirm that ADP-A2M4D8 is more potent and better engages the immune system, compared to the first-generation product Conclusions from the Phase 1 SURPASS Trial Data at ESMO Overview of Phase 1 SURPASS trial design About AdaptimmuneAdaptimmune is a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapy products for people with cancer. The Company’s unique SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell platform enables the engineering of T-cells to target and destroy cancer across multiple solid tumors. Forward-Looking StatementsThis release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA). These forward-looking statements involve certain risks and uncertainties. Such risks and uncertainties could cause our actual results to differ materially from those indicated by such forward-looking statements, and include, without limitation: the success, cost and timing of our product development activities and clinical trials and our ability to successfully advance our TCR therapeutic candidates through the regulatory and commercialization processes. For a further description of the risks and uncertainties that could cause our actual results to differ materially from those expressed in these forward-looking statements, as well as risks relating to our business in general, we refer you to our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 9, 2021 and our other SEC filings. The forward-looking statements contained in this press release speak only as of the date the statements were made and we do not undertake any obligation to update such forward-looking statements to reflect subsequent events or circumstances. Adaptimmune Contacts: Media Relations: Sébastien Desprez — VP, Corporate Affairs and CommunicationsT: +44 1235 430 583M: +44 7718 453 176Sebastien.Desprez@adaptimmune.com Investor Relations: Juli P. Miller, Ph.D. — VP, Investor RelationsT: +1 215 825 9310M: +1 215 460 8920Juli.Miller@adaptimmune.com

Cell TherapyImmunotherapy

13 Sep 2021

·endpts.com

German radiopharma forms another China joint venture; Urovant's Gemtesa passes blood pressure study

German biotech ITM is forming a joint venture with Chinese radiopharma player Chengdu Gaotong Isotope. This venture follows a strategic partnership between ITM and the China Isotope and Radiation Corporation (CIRC) which was initially formed in 2010 and further extended in November 2019 . The newly formed company is scheduled to start operations by the end of the year and will be located in Chengdu, China. This will be ITM’s second location in China after opening its first subsidiary in Shanghai earlier this year. “We are committed to further expanding our successful, long-term partnership with CIRC and are looking forward to increasing our global footprint in China,” said ITM CEO Steffen Schuster. Further details of the agreement were not disclosed. — Paul Schloesser California biotech Urovant’s Gemtesa has no clinically relevant effect on blood pressure and heart rate, according to the biotech . Urovant showed data from an outpatient study at the yearly meeting of the American Urological Association showing blood pressure and heart rate being similar between two groups of patients: one with a placebo for 28 days, and the other on daily Gemtesa. “We are delighted to present these important additional data confirming the efficacy and safety profile of Gemtesa,” said Urovant CMO Cornelia Haag-Molkenteller in a statement. According to the study, systolic blood pressure, diastolic blood pressure, and heart rate were generally similar between the two groups. There were no statistically significant or clinically relevant differences in mean daytime or mean 24-hour ambulatory systolic blood pressure, diastolic blood pressure, or heart rate after 28 days of treatment with Gemtesa compared with placebo. Part of Vivek Ramaswamy’s family of companies, the biotech’s overactive bladder drug Gemtesa hit the market late last year as Urovant’s first approved product. — Paul Schloesser Georgia regenerative medicine biotech MiMedx has results from two late-stage clinical trials on its treatment (micronized dehydrated Human Amnion Chorion Membrane, or mdHACM) for knee osteoarthritis and plantar fasciitis. The trials, in Phases IIb and III, respectively, did not hit the primary endpoints in either study. The osteoarthritis study did reveal varied efficacy signals between patients evaluated pre- and post-study, which will lead MiMedx to attempt confirmatory studies. As for the study on plantar fasciitis, MiMedx will not pursue a BLA with the FDA. “We look forward to further discussions with the FDA under the Regenerative Medicine Advanced Therapy process, and reviewing our next steps for continued clinical study of Purion processed mdHACM as a platform for regenerative medicine,” said MiMedx CEO Timothy Wright in a statement. MiMedx was in hot water late last year after the CEO and the COO at the time were respectively convicted of securities fraud and conspiracy. This happened after the FBI alleged that the company was fraudulently boosting its sales. — Paul Schloesser Fresh off a $3 billion deal with Roche to develop off-the-shelf T cell therapies, Adaptimmune is capitalizing on the momentum with a new data release it expects to present at #ESMO21 this weekend. In a Phase I study looking at 22 evaluable patients with MAGE-A4+ tumors “in the context of HLA-A*02,” Adaptimmune saw seven partial responses and one complete response, good for an overall response rate of 36.4%. The responses spanned five different indications including ovarian, head and neck, esophagogastric junction and bladder cancers, as well as synovial sarcoma. “It is no longer a question of whether our SPEAR T-cells are effective against a range of MAGE-A4 expressing tumors — they undoubtedly are,” CEO Adrian Rawcliffe said in a statement. “Now, our focus is on turning them into approved therapies.” Another 11 patients saw their disease stabilized on the therapy, while three saw disease progression. Adaptimmune reported that the data cutoff was August 2, saying 25 total patients had received the therapy at that point while 22 of the 25 made up Monday’s data readout. The biotech also noted it was encouraged by the initial durability results. Of the eight responders, five remain progression-free after a minimum of 24 weeks. — Max Gelman

Cell TherapyCollaborate

100 Deals associated with Alpha fetoprotein targeted T-cell therapy(Adaptimmune Ltd.)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Hepatocellular Carcinoma	Phase 1	US	Adaptimmune Ltd.	08 May 2017
Advanced Hepatocellular Carcinoma	Phase 1	FR	Adaptimmune Ltd.	08 May 2017
Advanced Hepatocellular Carcinoma	Phase 1	ES	Adaptimmune Ltd.	08 May 2017
Advanced Hepatocellular Carcinoma	Phase 1	GB	Adaptimmune Ltd.	08 May 2017
AFP expressing solid tumors	Phase 1	US	Adaptimmune Ltd.	08 May 2017
AFP expressing solid tumors	Phase 1	FR	Adaptimmune Ltd.	08 May 2017
AFP expressing solid tumors	Phase 1	ES	Adaptimmune Ltd.	08 May 2017
AFP expressing solid tumors	Phase 1	GB	Adaptimmune Ltd.	08 May 2017

Clinical Result

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Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03132792 (Corporate Publications) Manual	Phase 1	Liver Cancer	9	ADP-A2AFP	hmywzrikwy(qdmatkqpoh) = czqjpxivnu vkbtdczmaz (vucllnazdk ) View more	Positive	28 Aug 2020

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