On May 29, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the European Commission (EC) has approved Opdivo (nivolumab) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC) (Press release, Bristol-Myers Squibb, MAY 29, 2024, View Source [SID1234643780]). With this approval, Opdivo in combination with cisplatin and gemcitabine becomes the first concurrent immunotherapy-chemotherapy approved for the treatment of adult patients with unresectable or metastatic UC in the first-line setting in the European Union.

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"With today’s approval by the EC, we’re pleased to be able to offer Opdivo concurrently with chemotherapy to eligible patients with unresectable or metastatic UC," said Dana Walker, M.D., M.S.C.E., vice president and global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. "This is a major step forward for this patient population and reinforces our goal of advancing and delivering new options to patients with difficult-to-treat cancers. We extend our sincerest gratitude to the patients, their families, investigators and staff who contributed to this important research."

The EC’s decision is based on results from the CheckMate -901 trial studying Opdivo in combination with cisplatin and gemcitabine, which were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023. In CheckMate -901, Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy demonstrated statistically significant and clinically meaningful improvements in the primary efficacy endpoints of overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone, as assessed by Blinded Independent Central Review (BICR). The safety profile was consistent with the known safety profiles of the individual components of the regimen. No new safety concerns were identified.

"In the CheckMate -901 trial, the combination of Opdivo with cisplatin and gemcitabine improved overall survival, reduced the risk of disease progression or death by 28% versus chemo alone, and demonstrated deep and durable responses versus chemo alone," said Michiel Van der Heijden, M.D, Ph.D., medical oncologist and research group leader, Netherlands Cancer Institute. "These findings are significant and reinforce that concurrent Opdivo and chemotherapy should be considered as a new standard of care for the first line treatment of eligible patients with this difficult-to-treat cancer."

This approval by the EC for Opdivo in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic UC is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway.

This approval of Opdivo in combination with cisplatin and gemcitabine based on results of the CheckMate -901 trial, further supports the EU’s previous approval of Opdivo for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing radical resection. In addition to this approved indication in UC, Opdivo-based options are also approved for treatment of 10 different cancer types in the EU including: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma (EAC), esophageal or gastroesophageal junction (GEJ) cancer, colorectal cancer, mesothelioma, renal cell carcinoma, esophageal squamous cell carcinoma (ESCC) and squamous cell cancer of the head and neck.

CheckMate -901 Efficacy and Safety Results

With a median follow up of approximately 33 months of the CheckMate -901 trial, results showed:

OS (overall survival; primary endpoint): Opdivo in combination with cisplatin and gemcitabine reduced the risk of death in patients by 22%, demonstrating a median OS of 21.7 months versus 18.9 months with cisplatin-gemcitabine alone (HR (hazard ratio): 0.78; 95% CI (confidence interval): 0.63, 0.96; p=0.0171).
PFS (progression-free survival; primary endpoint): Risk of disease progression or death reduced by 28%, with a median PFS of 7.9 months compared to 7.6 months with cisplatin-gemcitabine alone (HR 0.72; 95% CI: 0.59, 0.88; p=0.0012).
ORR (overall response rate; secondary endpoint): Opdivo in combination with cisplatin and gemcitabine resulted in an ORR of 57.6% (n=175) (95% CI: 51.8, 63.2) versus 43.1% (n=131) (95% CI: 37.5, 48.9) with cisplatin-gemcitabine alone.
CR (complete response) rate and PR (partial response) rate (secondary endpoints): The CR rate and PR rate seen in patients treated with Opdivo in combination with cisplatin and gemcitabine was 22% (n=66) and 36% (n=109), respectively, versus 12% (n=36) and 31% (n=95) with cisplatin-gemcitabine alone.
About CheckMate -901

CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy (ipilimumab) or Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy compared to standard-of-care chemotherapy alone, in patients with untreated, unresectable or metastatic urothelial cancer.

In CheckMate -901, evaluating Opdivo with cisplatin and gemcitabine vs. standard-of-care chemotherapy alone, a total of 608 patients eligible for cisplatin-based chemotherapy were randomized to receive either Opdivo 360 mg in combination with cisplatin and gemcitabine every three weeks for up to six cycles followed by 480 mg/Q4 Opdivo monotherapy every 4 weeks until disease progression or death up to a maximum of two years, or cisplatin-gemcitabine alone every three weeks for up to six cycles. The primary endpoints of this study are overall survival (OS) and progression-free survival (PFS).

The OS and PFS outcomes for patients eligible for cisplatin-based chemotherapy are based on the final efficacy analyses of these endpoints.

The CheckMate -901 primary study, evaluating Opdivo plus Yervoy vs. standard-of-care cisplatin- or carboplatin-based chemotherapy in patients with untreated, unresectable or metastatic urothelial carcinoma remains ongoing.

Select Safety Profile from CheckMate -901

Serious adverse reactions occurred in 48% of patients receiving Opdivo with chemotherapy.1 The most frequent serious adverse reactions reported in ≥2% of patients who received Opdivo with chemotherapy were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decreased (2.3%).1 The most common adverse reactions (reported in ≥20% of patients) were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy.1 Fatal adverse reactions occurred in 3.6% patients who received Opdivo with chemotherapy; these included sepsis (1%).1 Opdivo and/or chemotherapy were discontinued in 30% of patients and were delayed in 67% of patients for an adverse reaction.

About Urothelial Carcinoma

Bladder cancer is the ninth most common cancer in the world, with more than 600,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but rates of recurrence and disease progression are high. Approximately 50% of patients who undergo radical surgery will experience disease recurrence, especially within the first two to three years after surgical removal of the bladder or kidney. For patients whose disease recurs as metastatic cancer, the prognosis is poor, with a median overall survival of approximately 12 to 14 months when treated with systemic therapy.

On May 29, 2024 bluebird bio, Inc. (Nasdaq: BLUE) reported that O. James Sterling, has been appointed chief financial officer (CFO), effective June 10, 2024. Mr. Sterling most recently served as chief financial officer of Renalytix plc, a diagnostics company focused on clinical management of kidney disease (Press release, bluebird bio, MAY 29, 2024, View Source [SID1234643779]).

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"We are thrilled to welcome James to bluebird bio. We are confident that his extensive experience in the healthcare sector and knowledge of the capital markets will position us well as we work to prove the commercial gene therapy model, and demonstrate progress on our path to profitability," said Andrew Obenshain, chief executive officer, bluebird bio.

"It is an honor to be joining bluebird bio, a company that has pioneered gene therapy development over the past decade, and today is at the forefront of gene therapy commercialization," said O. James Sterling. "I look forward to working alongside others in the flock to drive growth, realize value for shareholders, and most importantly, support bluebird in its mission to bring transformative gene therapies to patients and their families."

Mr. Sterling was previously managing partner at Renwick Capital LLC, and managing director at investment banks Brock Capital Group LLC and Aleutian Capital Group. He also serves as a board director for a fund managed by Star Mountain Capital. Mr. Sterling has experience as a management consultant at Booz Allen Hamilton. He received his B.A. from Boston University and an MBA from Columbia Business School.

Mr. Sterling succeeds Chris Krawtschuk, who joined bluebird bio as chief financial officer in 2022. The transition will be effective June 10, 2024.

"I’d like to thank Chris for his contributions to the company over the past two years. We are particularly appreciative of his leadership role in accelerating critical cash flow into the company, as well as the completion of two equity raises and a debt agreement, which significantly extended the Company’s cash runway and strengthened our financial position during his tenure," said Obenshain.

On March 26, 2024, bluebird announced that it will restate its consolidated financial statements for the first three quarters and full-year 2022, as well as the first three quarters of 2023. As a result, the Company’s Annual Report Form 10-K for 2023 and its Q1 2024 Form 10-Q have been delayed. The Company is continuing to work expeditiously to complete these filings. Consistent with previous updates, the restatement is not expected to impact the Company’s cash position or revenue. Mr. Sterling will transition to oversee the restatement process upon his start date.

On May 29, 2024 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, reported that its Chief Executive Officer, Mark Velleca, M.D., Ph.D., will participate in a fireside chat at the Jefferies Global Healthcare Conference taking place June 4-6, 2024, in New York, NY (Press release, Black Diamond Therapeutics, MAY 29, 2024, View Source [SID1234643778]).

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Presentation details are as follows:

7:30-7:55am ET on Wednesday, June 5
A live webcast of the event can be accessed by visiting the investors relations section of the Company’s website, www.blackdiamondtherapeutics.com. A replay of the webcast will also be available and archived for 90 days following the event.

On May 29, 2024 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, reported preclinical data supporting the potential of ATA3219, an allogeneic, anti-CD19 chimeric antigen receptor (CAR) T-cell therapy candidate for the treatment of B-cell driven autoimmune diseases (Press release, Atara Biotherapeutics, MAY 29, 2024, View Source [SID1234643775]). Findings demonstrate that ATA3219 maintains comparable cytotoxic function and potency while inducing lower levels of pro-inflammatory cytokines compared to autologous benchmark CD19 CAR T cells. The data will be presented in a poster session at the International Society for Cell & Gene Therapy (ISCT) 2024 Annual Meeting taking place May 29 to June 1, 2024, in Vancouver, Canada.

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ATA3219 consists of allogeneic CD19-directed CAR EBV T cells that have been optimized to offer a potential best-in-class profile and off-the-shelf availability. It incorporates multiple clinically validated technologies including a modified CD3ζ signaling domain (1XX) that sustains potent effector function while modulating activation and inflammation; a less differentiated phenotype for robust expansion and persistence; and no modification of the endogenous T-cell receptor (no gene editing) as a key T-cell survival signal.

"Following exciting early clinical data with autologous CD19 CAR T in autoimmune patients, we believe there is an opportunity to further improve long-term efficacy, reduce toxicity and simplify treatment through our optimized allogeneic CD19 CAR T cells," said Cokey Nguyen, Ph.D., Executive Vice President, Chief Scientific & Technical Officer at Atara. "We are pleased to share promising preclinical data that shows ATA3219 mediates robust B-cell depletion against SLE and multiple sclerosis patient derived immune cells. Importantly, ATA3219 is an off-the-shelf option that shows a favorable inflammatory profile that may lead to less toxicity and improved tolerability in the clinic. We look forward to continued evaluation of ATA3219 for the treatment of non-Hodgkin’s lymphoma, lupus nephritis, and in a recently announced cohort expansion for severe SLE without lymphodepletion."

The ATA3219 preclinical data demonstrate potent CD19 antigen-specific cytotoxic activity against CD19+ targets in vitro and in vivo. Data highlights comparing ATA3219 to an autologous benchmark CD19 CAR T include:

More robust central memory cell population as a result of the 1XX co-stimulatory domain and optimized manufacturing process
Complete CAR-mediated B-cell depletion against SLE and MS patient peripheral blood mononuclear cells with comparable potency
Reduced inflammatory profile with decreased secretion of pro-inflammatory cytokines IFN-γ, TNF-α and IL-6, as well as T helper 2 (Th2) cytokines IL-4 and IL-5, while achieving comparable B-cell depletion
These preclinical results support advancing ATA3219 towards clinical evaluation in patients with B-cell driven autoimmune diseases.

ATA3219 is currently being investigated in a Phase 1 trial (NCT06256484) for the treatment of relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL) with initial clinical data expected in the fourth quarter 2024. Additionally, ATA3219 will be evaluated in a multi-center, Phase 1, open-label, single-arm, dose-escalation study for the treatment of LN with lymphodepletion and a separate cohort in severe SLE without lymphodepletion. Initial data for LN and severe SLE without lymphodepletion is anticipated in the first half and second half of 2025, respectively.

Poster Presentation Details:
Title: ATA3219: Allogeneic CD19 CAR EBV T Cells for the Treatment of B-Cell Driven Autoimmune Diseases
Presenting Author: Alfonso Brito, M.S., Preclinical & Translational Sciences, Atara Biotherapeutics, Inc., Thousand Oaks, CA
Date & Time: Wednesday, May 29, 2024, at 7:00 – 8:30 p.m. PDT
Poster Number: 1025
Session: Poster Networking Session 1
Location: Exhibit & Poster Hall, Vancouver Convention Centre, West Building

About ATA3219

ATA3219 combines the natural biology of unedited T cells with the benefits of an allogeneic therapy. It consists of allogeneic Epstein-Barr virus (EBV)-sensitized T cells that express a CD19 CAR construct for the treatment of CD19+ relapsed or refractory B-cell malignancies, including B-cell non-Hodgkin’s lymphoma and B-cell mediated autoimmune diseases including systemic lupus erythematosus (SLE) and lupus nephritis. ATA3219 has been optimized to offer a potential best-in-class profile, featuring off-the-shelf availability. It incorporates multiple clinically validated technologies including a modified CD3ζ signaling domain (1XX) that optimizes expansion and mitigates exhaustion, enrichment during manufacturing for a less differentiated phenotype for robust expansion and persistence and retains the endogenous T-cell receptor without gene editing as a key survival signal for T cells contributing to persistence.

Next-Generation Allogeneic CAR T Approach

Atara is focused on applying Epstein-Barr virus (EBV) T-cell biology, featuring experience in over 600 patients treated with allogeneic EBV T cells, and novel chimeric antigen receptor (CAR) technologies to meet the current limitations of autologous and allogeneic CAR therapies head-on by advancing a potential best-in-class CAR T pipeline in oncology and autoimmune disease. Unlike gene-edited approaches aimed at inactivating T-cell receptor (TCR) function to reduce the risk for graft-vs-host disease, Atara’s allogeneic platform maintains expression of the native EBV TCR that promote in vivo functional persistence while also demonstrating inherently low alloreactivity due to their recognition of defined viral antigens and partial human leukocyte antigen (HLA) matching. A molecular toolkit of clinically-validated technologies—including the 1XX costimulatory domain designed for better cell fitness and less exhaustion while maintaining stemness—offers a differentiated approach to addressing significant unmet need with the next generation CAR T.

On May 29, 2024 Arbutus Biopharma Corporation (Nasdaq: ABUS), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop a functional cure for people with chronic hepatitis B virus (cHBV) infection, reported that the Arbutus management team will present at and host one-on-one meetings at the following upcoming investor conference being held in New York (Press release, Arbutus Biopharma, MAY 29, 2024, View Source [SID1234643774]):

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Jefferies Global Healthcare Conference: Formal Presentation on June 5, 2024 at 9:30 am ET

To access the live webcast of the presentation, please visit: View Source An archived replay of the webcast will be available on the Arbutus website for a limited time after the event.