Combination of Encorafenib Plus Cetuximab in a Neoadjuvant Setting in Patients With Braf v600e-mutates Localised Colon or Upper Rectum Cancer (Neoraf Study)
This is a pilot trial which aims to assess the concept of anti-BRAF neoadjuvant treatment (encorafenib) in combination with cetuximab in patients with colon cancer or rT3/T4 supra-peritoneal upper rectal cancer based on a pre-operative CT-scan. About 10% of patients will have a mutated BRAF V600E tumour and the objective is to include 30 patients with this mutation. If the tumour is not confirmed as a carrier of the BRAF V600E mutation or has an RAS mutation according to centralised assessment, treatment will be discontinued in this patient and cancer surgery will be organised as soon as possible. The patient will be excluded from the statistical analysis and will be replaced by a new patient in order to obtain 30 patients with confirmed BRAF V600E mutation and RAS wild type . It should be noted that less than a 3% discrepancy between the numbers of local laboratory results and central analysis results, has been reported in over 600 BRAF V600E mutated colon cancers in the BEACON CRC study. Based on these figures, there should be 0 or 1 patient with discrepant results in the study presented here. Furthermore, in the hypothetical case of a patient who is an early permanent discontinuation of the study prior to surgery, this patient will be replaced in order to obtain a total of 30 patients who underwent surgery after neoadjuvant treatment.
A Randomized Phase II Study to Evaluate the Incidence of Discontinuations Due to Diarrhoea at 3 Cycles in Patients With Early-stage HER2-positive (HER2+), Hormone Receptor-positive (HR+) Breast Cancer Treated With Neratinib Plus Loperamide Prophylaxis Versus Neratinib With Initial Dose Escalation Plus PRN Loperamide Prophylaxis Versus Neratinib Plus Loperamide Plus Colesevelam Prophylaxis "DIANER Study"
A Randomized Phase II Study to Evaluate the Incidence of Discontinuations due to Diarrhoea at 3 Cycles in patients with Early-stage HER2-positive (HER2+), Hormone Receptor-positive (HR+) Breast Cancer treated with Neratinib plus Loperamide prophylaxis versus Neratinib with Initial Dose Escalation plus PRN Loperamide prophylaxis versus Neratinib plus Loperamide plus Colesevelam prophylaxis.
A PHASE 1, RANDOMIZED, OPEN-LABEL STUDY IN HEALTHY PARTICIPANTS TO ESTIMATE THE BIOAVAILABILITY OF TWO NEW ENCORAFENIB FORMULATIONS RELATIVE TO THE CURRENT FORMULATION AND TO EVALUATE THE EFFECT OF A PROTON-PUMP INHIBITOR ON ENCORAFENIB PLASMA PHARMACOKINETICS
Relative bioavailability study to evaluate the pharmacokinetics of two new encorafenib formulations
THOUSAND OAKS, Calif.--(BUSINESS WIRE)-- Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, today announced the closing of the expanded global partnership with Pierre Fabre Laboratories for tabelecleucel (tab-cel® or EBVALLOTM). Building on the earlier partnership announced in October 2021 to commercialize tab-cel in Europe, this transaction provides Pierre Fabre Laboratories with the development, manufacturing, and commercialization rights for tab-cel in the United States and all remaining markets.
“We are pleased to announce the closing of the transaction with Pierre Fabre Laboratories who are committed to expanding the reach of tab-cel to patients in the U.S. and across the globe,” said Pascal Touchon, President and Chief Executive Officer of Atara. “Atara’s priority is to now submit the tab-cel BLA filing package, while initiating our first clinical study with ATA3219, a potential best-in-class allogeneic off-the-shelf CD19 CAR T with unique features.”
With the closing of the transaction, Atara will receive approximately USD 27 million in cash upfront and initial inventory purchase. Under the agreement, Atara has the potential to receive up to a total of USD 640 million and significant double-digit tiered royalties on net sales, including up to USD 100 million in potential regulatory milestones through BLA approval. In addition, Pierre Fabre Laboratories will reimburse Atara for expected tab-cel global development costs through the Biologics License Application (BLA) transfer, and purchase future tab-cel inventory through the manufacturing transfer date.
Substantially all tab-cel manufacturing, clinical, and regulatory activities are planned to transition from Atara to Pierre Fabre Laboratories at the time of BLA transfer.
Atara plans to submit the BLA to the U.S. Food and Drug Administration (FDA) for tab-cel for the treatment of post-transplant lymphoproliferative disease (PTLD) in the second quarter of 2024.
About Atara Biotherapeutics, Inc.
Atara is harnessing the natural power of the immune system to develop off-the-shelf cell therapies for difficult-to-treat cancers and autoimmune conditions, that can be rapidly delivered to patients within days. With cutting-edge science and differentiated approach, Atara is the first company in the world to receive regulatory approval of an allogeneic T-cell immunotherapy. Our advanced and versatile Epstein-Barr virus (EBV) T-cell platform does not require T-cell receptor or HLA gene editing and forms the basis of a diverse portfolio of investigational therapies that target EBV, the root cause of certain diseases, in addition to next-generation AlloCAR-Ts designed for best-in-class opportunities across a broad range of non-EBV-associated liquid and solid tumors. Atara is headquartered in Southern California. For more information, visit atarabio.com and follow @Atarabio on X (formerly known as Twitter) and LinkedIn.
This press release contains or may imply "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. For example, forward-looking statements include statements regarding: (1) the development, timing and progress of tab-cel®, including a potential BLA, the potential characteristics and benefits of tab-cel®, and the progress and results of, prospects for, and closing of the expanded global partnership with Pierre Fabre Laboratories involving tab-cel®, and the potential financial benefits to Atara as a result of the expanded global partnership with Pierre Fabre Laboratories; (2) the development, timing and progress of Atara’s AlloCAR-T programs, including ATA3219; (3) Atara’s cash runway; and (4) Pierre Fabre Laboratories’ activities relating to tab-cel and the timing thereof. Because such statements deal with future events and are based on Atara’s current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Atara could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, risks and uncertainties associated with the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success; the COVID-19 pandemic and the wars in Ukraine and the Middle East, which may significantly impact (i) our business, research, clinical development plans and operations, including our operations in Southern California and Denver and at our clinical trial sites, as well as the business or operations of our third-party manufacturer, contract research organizations or other third parties with whom we conduct business, (ii) our ability to access capital, and (iii) the value of our common stock; the sufficiency of Atara’s cash resources and need for additional capital; and other risks and uncertainties affecting Atara’s and its development programs, including those discussed in Atara’s filings with the Securities and Exchange Commission , including in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of the Company’s most recently filed periodic reports on Form 10-K and Form 10-Q and subsequent filings and in the documents incorporated by reference therein. Except as otherwise required by law, Atara disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.
The partnership intends to develop the FoundationOne CDx and FoundationOne Liquid CDx genomic tests as companion diagnostics for treatment of patients with non-small cell lung cancer
Foundation Medicine and Pierre Fabre Laboratories to develop companion diagnostics for NSCLC treatment. (Credit: Testalize.me on Unsplash)
US-based Foundation Medicine and Pierre Fabre Laboratories have agreed to partner on developing companion diagnostics for new targeted therapies for the treatment of patients with non-small cell lung cancer (NSCLC).
The partnership intends to develop the FoundationOne CDx and FoundationOne Liquid CDx genomic tests as companion diagnostics for NSCLC treatment.
Together, the companies will apply for regulatory approval for Foundation Medicine’s assays that detect mutations, such as BRAFV600E.
Patients will be identified for potential treatment in the European Union using Pierre Fabre’s BRAF/MEK inhibitor combination regimen, which includes BRAFTOVI (encorafenib) and MEKTOVI (binimetinib).
This combination therapy was assessed in a clinical trial supported by France-based Pierre Fabre and sponsored by Pfizer.
It is currently being examined by the European Medicines Agency for patients with advanced NSCLC that has a BRAFV600 mutation.
Pierre Fabre medical and patient consumer department head Núria Perez-Cullell said: “Today, as the number of indications and approvals in oncology grow rapidly, companion diagnostics provide information that is critical for the safe and effective use of targeted therapies. And that’s why we are excited to work with Foundation Medicine.
“Thanks to those companion diagnostics, physicians will have comprehensive, reliable information about what is driving a patient’s cancer, such as BRAFV600E mutations, so they can make personalised treatment decisions.”
The US Food and Drug Administration (FDA) has approved FoundationOne CDx and FoundationOne Liquid CDx as in-vitro diagnostic tools for the detection of potentially targetable mutations in solid tumour samples derived from blood and tissue.
Foundation Medicine is said to have the only FDA-approved portfolio of complete genomic profiling tests.
The range offers doctors both blood- and tissue-based testing options to identify genomic alterations such as BRAFV600E to help guide individualised therapy decisions.
The company has shown initial success in navigating the new In Vitro Diagnostics Regulation (IVDR) in Europe via several global trials or using patient samples from European Union member states.
Foundation Medicine chief biopharma business officer Troy Schurr said: “High-quality companion diagnostics play a crucial role in helping physicians match their patients with targeted treatment options.
“We are excited to support Pierre Fabre Laboratories in offering more treatment options for cancer patients, and to increase access to precision therapies in the European Union.”
Atara Biotherapeutics will scale back investment in ATA188 after the investigational off-the-shelf, allogeneic T-cell immunotherapy failed to meet the primary endpoint of a Phase II study in non-active progressive multiple sclerosis. "We are surprised and deeply disappointed with the results,” remarked CEO Pascal Touchon, which sent the company’s shares down as much as 45%.The EMBOLD trial included 103 adults with progressive multiple sclerosis who received two cycles of treatment with ATA188 or placebo and followed for 12 months. The study’s main goal was confirmed disability improvement (CDI) by expanded disability status scale (EDSS) at 12 months.According to Atara, ATA188 was associated with a 6% disability improvement in EMBOLD, while the improvement for placebo was 16%. The company noted that it is reviewing the data, given the “substantially greater than expected” result for placebo and a 33% disability improvement seen in an earlier Phase I study of ATA188. “We are further evaluating the EMBOLD data…however we anticipate stopping the study as no treatment benefit was observed,” Touchon added.Atara said that it will significantly reduce its expenses on ATA188 and instead focus resources on advancing its allogeneic CAR-T pipeline. Earlier this month, the company announced an expanded partnership with Pierre Fabre Laboratories for tabelecleucel (tab-cel), which is under investigation for Epstein-Barr virus-associated post-transplant lymphoproliferative disease.At the time of disclosing the Pierre Fabre deal, Atara indicated that it will cut its workforce by around 30% as part of a strategic restructuring. “Following anticipated additional payments and significant double-digit royalties from the recently expanded tab-cel partnership with Pierre Fabre, we are currently well positioned with a cash runway well beyond upcoming milestones,” Touchon said.