1stOncology™: Cancer Intelligence Service – Page 3358 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Novartis radioligand therapy Lutathera® FDA approved as first medicine specifically for pediatric patients with gastroenteropancreatic neuroendocrine tumors

On April 23, 2024 Novartis reported that the U.S. Food and Drug Administration (FDA) approved Lutathera (USAN: lutetium Lu 177 dotatate / INN: lutetium (177Lu) oxodotreotide) for the treatment of pediatric patients 12 years and older with somatostatin receptor-positive (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut NETs (Press release, Novartis, APR 23, 2024, View Source [SID1234642248]). This approval makes Lutathera the first therapy specifically reviewed and approved for use in pediatric patients with GEP-NETs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"Lutathera is now the very first therapy approved specifically for children with GEP-NETs, offering new hope to young patients living with this rare cancer," said Tina Deignan, Therapeutic Area Head, Oncology US. "Radioligand therapies have extraordinary potential to shape the future of cancer care. With this approval, we have taken another vital step toward fulfilling that vision, strengthening our commitment to researching and developing the RLT platform across multiple cancer types and treatment settings."

NETs are a type of cancer that originates in neuroendocrine cells throughout the body and are commonly considered slow-growing malignancies1. The diagnosis of NETs is often delayed due to the inactive nature of the disease, and approximately 10% to 20% of pediatric patients are diagnosed with metastatic disease2,3. Even though NETs are an orphan disease, their incidence has increased over the past several decades1,4-6.

"While GEP-NETs in children and adolescents are rare, the impact can be devastating. Today’s approval addresses a critical need for new treatment options for these vulnerable patients," said Dr. Theodore Laetsch, trial investigator and Director, Developmental Therapeutics Program, Children’s Hospital of Philadelphia (CHOP), a NETTER-P clinical trial site. "The introduction of radioligand therapy significantly advanced how we treat GEP-NETs, and I’m encouraged that younger patients now have the potential to benefit from this innovation."

The approval was based on the NETTER-P trial, which evaluated Lutathera in patients aged 12 to <18 years old with SSTR+ GEP-NETs7. The study reported a safety profile consistent with the adult population studied in NETTER-1, the pivotal trial for approval of Lutathera in adults. In addition, the estimated radiation absorbed dose in pediatric patients was within established organ thresholds for external beam radiation and comparable to that in adults for the approved dose.

About Lutathera
Lutathera (lutetium Lu 177 dotatate) is approved in the US for the treatment of adults and children 12 years and older with SSTR-positive GEP-NETs, including those in the foregut, midgut and hindgut, an indication which includes the populations studied in the randomized, controlled Phase III trials NETTER-1 and NETTER-2. Lutathera is also approved in Europe for unresectable or metastatic, progressive, well-differentiated (G1 and G2), SSTR-positive GEP-NETs in adults, and in Japan for SSTR-positive NETs

Defence’s Accutox Anti-Cancer Arm-002 Vaccine Exhibits Potent Antigen Presentation

On April 23, 2024 Defence Therapeutics Inc. ("Defence" or the "Company"), (CSE: DTC, OTCQB: DTCFF, FSE: DTC), a Canadian biopharmaceutical company developing novel immune-oncology therapeutics and drug delivery technologies, reported that its second-generation ARMTM anti-cancer vaccine using AccuTOX, called ARM-002TM, is therapeutically effective against pre-established melanoma when combined with the anti-PD-1 immune-checkpoint inhibitor (Press release, Defence Therapeutics, APR 23, 2024, View Source;utm_medium=rss&utm_campaign=defences-accutox-anti-cancer-arm-002-vaccine-exhibits-potent-antigen-presentation [SID1234642247]).

Defence’s application of reprogrammed mesenchymal stromal cells ("MSCs") represents a leading vaccination platform due to its ease in manufacturing and the therapeutic potency that this allogeneic off-the-shelf vaccine can provide. The use of AccuTOX to reprogram these MSCs relies mainly on the induction of protein aggregation. This process is known to induce the activation of the unfolded protein response, a cellular defense mechanism normally triggered to destroy any captured protein aggregates due to the toxicity and disturbance it causes to cell integrity.

"Defence’s AccuTOX was initially known for its ability to kill cancer cells. In addition, our team found that at specific doses, AccuTOX forms protein aggregates when mixed with tumor lysate, a process that pushes MSCs to degrade these intracellular complexes resulting in potent antigen presentation." says Mr. Plouffe, Chief Executive Officer of Defence Therapeutics.

The original ARMTM vaccine was potent against melanoma. The ARM-002TM vaccine is even more potent, as it actually requires 10x less protein. This was confirmed both in vitro (using antigen cross-presentation assay) and in vivo where ARM-002TM pulsed with 0.05 mg/ml of tumor lysate resulted in similar outcomes compared to ARM-002TM generated using a dose of 0.5 mg/ml. In addition, the potency of the ARM-002TM vaccine was comparable in both male and female mice, with no noticeable side effects detected in vaccinated animals. Defence is currently testing the ARM-002TM vaccine on "hard-to-treat" cancers such as pancreatic, colon and ovarian cancers. These results will set the target indication for the Phase I trials, and it also shows how versatile and adaptable the ARM-002TM anti-cancer vaccine is.

Curium Enrolls First Prostate Cancer Patients in its Phase 3 SOLAR Trials

On April 23, 2024 Curium, a world leader in nuclear medicine, reported that it has successfully enrolled and scanned patients in its SOLAR clinical trials (Press release, Curium, APR 23, 2024, View Source [SID1234642246]):

The first trial is SOLAR-STAGE: a Phase 3, multicenter, open-label study to evaluate the diagnostic performance of copper Cu 64 PSMA I&T PET/CT in staging of men with newly diagnosed unfavorable intermediate-risk, high-risk or very-high-risk prostate cancer electing to undergo radical prostatectomy with pelvic lymph node dissection.
The second study, SOLAR-RECUR: a Phase 3, multicenter, open-label study to evaluate the diagnostic performance of copper Cu 64 PSMA I&T PET/CT in men with suspected biochemical recurrence of prostate cancer after radical prostatectomy or radiation therapy.
These clinical trials are currently enrolling patients at sites across the U.S. and will be opening clinical trial sites in Europe later this year.

Sakir Mutevelic, MD, Curium’s Chief Medical Officer said: "The successful start of patient enrollment is a significant step forward for Curium’s Phase 3 SOLAR-STAGE and SOLAR-RECUR clinical trials. As we continue Curium’s journey to redefine the experience of cancer through our trusted legacy in nuclear medicine, we look forward to building on our well-established and successful 64-Cu diagnostic imaging platform."

Amy Bartalotta, Vice President of Clinical Operations added: "To ensure that the SOLAR clinical trials recruit a diverse set of patients – including minority groups that are often more affected by and less likely to be screened for prostate cancer – we have 50 sites in the U.S. and over 30 sites in Europe participating in these trials. We are pleased to announce the first patients enrolled and scanned were at XCancer under the direction of Dr. Luke Nordquist. We look forward to additional trial sites scanning patients across the U.S. and Europe in the coming months."

For more information about the SOLAR-STAGE (NCT06235151) and SOLAR-RECUR (NCT06235099) studies visit www.solarclinicaltrials.com or contact Curium’s Clinical Trial team directly at [email protected] with questions or to locate a clinical trial site near you.

BeiGene Receives European Commission Approval for Tislelizumab as Treatment for Non-Small Cell Lung Cancer

On April 23, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported that the European Commission (EC) has approved tislelizumab as a treatment for non-small cell lung cancer (NSCLC) across three indications, including first- and second-line use (Press release, BeiGene, APR 23, 2024, View Source [SID1234642245]).

"Tislelizumab is foundational for BeiGene’s solid tumor portfolio and has demonstrated its potential across multiple tumor types, including NSCLC, in which there remains a significant unmet need at all stages of the disease," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "Today’s EC authorization marks the second in the region for tislelizumab, with both NSCLC and locally advanced or metastatic esophageal squamous cell carcinoma now approved in the European Union. Second-line use in ESCC was also approved just weeks ago by the U.S. Food and Drug Administration, putting us well on our way to fulfilling our commitment to bring this innovative therapy to many more patients around the world."

The approved indications for tislelizumab are:

In combination with carboplatin and either paclitaxel or nab-paclitaxel for the first-line treatment of adult patients with squamous NSCLC who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.
In combination with pemetrexed and platinum-containing chemotherapy for the first-line treatment of adult patients with non-squamous NSCLC whose tumors have PD-L1 expression on ≥50% of tumor cells with no EGFR or ALK positive mutations and who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.
As monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC after prior platinum-based therapy. Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before receiving tislelizumab.
"Non-small cell lung cancer remains one of the most common and deadly cancers in Europe, with 50% of patients diagnosed already progressed to advanced stages, making it difficult to treat," said Luis Paz-Ares, M.D., Ph.D., Head of the Medical Oncology Service at the Hospital Universitario 12 de Octubre, Madrid. "Across three Phase 3 studies, tislelizumab has been shown to improve outcomes for patients with certain types of NSCLC, providing a new option for those facing the disease."

Tislelizumab was approved for these NSCLC indications under the brand name TIZVENI. BeiGene plans to combine the NSCLC indications with the second-line ESCC indication under the brand name TEVIMBRA, which will launch in the first EU countries later in 2024. TEVIMBRA is approved in the U.S. and EU for advanced or metastatic ESCC after prior chemotherapy and is under review by the European Medicines Agency and the U.S. Food and Drug Administration as a first-line treatment for patients with unresectable, recurrent, locally advanced or metastatic ESCC and for first-line gastric or gastroesophageal junction cancers.

The EC approval is based on the results from three Phase 3 studies in the RATIONALE program that enrolled 1,499 patients:

RATIONALE 307 (NCT03594747) is an open-label, randomized Phase 3 trial that enrolled 360 patients with advanced squamous NSCLC. The study met its primary endpoint, with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in progression free survival (PFS), as well as higher objective response rates and a manageable safety/tolerability profile, regardless of PD-L1 expression. The most common grade ≥3 treatment emergent adverse events (TEAEs) were decreased neutrophil levels, neutropenia and leukopenia. See full study results published in JAMA Oncology.
RATIONALE 304 (NCT03663205) is an open-label, randomized Phase 3 trial that enrolled 334 patients with locally advanced or metastatic non-squamous NSCLC. The study met its primary endpoint, with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in PFS compared to chemotherapy (HR: 0.65 [95% CI: 0.47-0.91]; P=0.0054) along with higher response rates and longer response duration. The most common grade ≥3 TEAEs were associated with chemotherapy and included neutropenia and leukopenia. See full study results published in the Journal of Thoracic Oncology.
RATIONALE 303 (NCT03358875) is an open-label, randomized Phase 3 trial with tislelizumab versus docetaxel that enrolled 805 patients with advanced NSCLC who progressed on prior platinum-based chemotherapy. The study met its primary endpoint, with second- or third-line tislelizumab resulting in statistically significant and clinically meaningful improvement in overall survival compared with docetaxel in the intent-to-treat population (HR: 0.66 [95% CI: 0.56-0.79]; P<0.0001), regardless of PD-L1 expression. The most commonly reported grade ≥3 TEAEs were pneumonia, anemia and dyspnea. See full study results published in the Journal of Thoracic Oncology.
BeiGene has launched more than 17 potentially registration-enabling trials with tislelizumab, of which 11 Phase 3 randomized trials and four Phase 2 trials have already had positive readouts. Through these trials, tislelizumab has demonstrated its potential to deliver clinically meaningful improvements in survival benefits and quality of life for hundreds of thousands of cancer patients across a range of tumor types – in many cases, regardless of PD-(L)1 status – both as monotherapy and in combination with other regimens. More than 900,000 patients have been prescribed tislelizumab globally to date.

About NSCLC

Lung cancer is the second most common type of cancer and the leading cause of cancer-related death worldwide.1 Lung cancer is the third most common cancer in Europe; NSCLC represents 85–90% of all lung cancers.2 In 2020, the number of new cases of lung cancer diagnosed in Europe was estimated at 477,534.3

About Tislelizumab

Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.

Important Safety Information

The full European Summary of Product Characteristics (SmPC) for the NSCLC indications for tislelizumab, which includes safety data for NSCLC and ESCC, is available from the European Medicines Agency.

Be Biopharma to Present at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting

On April 23, 2024 Be Biopharma, Inc. ("Be Bio"), a company pioneering the development of engineered B Cell Medicines (BCMs), reported that it will present at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 27th Annual Meeting being held May 7-11, 2024, in Baltimore, MD (Press release, Be Biopharma, APR 23, 2024, View Source [SID1234642243]).

Details regarding the Be Biopharma presentation at the conference are as follows:

Title: CRISPR/Cas9-based precision B cell gene engineering coupled with artificial intelligence-guided protein design produces active and sustained levels of tissue nonspecific alkaline phosphatase for the treatment of Hypophosphatasia

Presenter: Monika Musial-Siwek, Ph.D., Director, Protein Sciences, Be Biopharma

Date: May 10, 2024

Time: 12:00 PM ET

Session Title: Friday Posters: Musculo-Skeletal Diseases
Session Room: Exhibit Hall
Final Abstract Number: 1649

The abstract highlights Be Bio’s novel approach using engineered B-cell Medicines (BCMs) as a potential new treatment for Hypophosphatasia (HPP), a genetic disorder characterized by loss-of-function mutations in the ALPL gene which impairs the mineralization of bones. Researchers used CRISPR/Cas9 precision gene engineering and artificial intelligence-guided protein design to modify primary human B cells to produce tissue nonspecific alkaline phosphatase (ALP), an enzyme deficient in people living with HPP. The nonclinical data demonstrates the engineered BCM successfully produces active ALP , highlighting the therapeutic potential of the BCM platform as a novel treatment modality for HPP. BCMs have key attributes of plasma cells, including natural longevity, high levels of protein secretion, the ability to engraft without host preconditioning, and the ability to be re-dosed, making them an attractive platform for sustained supply of biologics.

For more information, please visit the conference website View Source

About Engineered B Cell Medicines – A New Class of Cellular Medicines

The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas.