Imfinzi approved in the US for the treatment of resectable non-small cell lung cancer before and after surgery

On August 16, 2024 AstraZeneca reported that Imfinzi (durvalumab) in combination with chemotherapy has been approved in the US for the treatment of adult patients with resectable early-stage (IIA-IIIB) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements (Press release, AstraZeneca, AUG 16, 2024, View Source [SID1234645947]). In this regimen, patients are treated with Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery.

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The approval by the Food and Drug Administration (FDA) was based on positive results from the pivotal AEGEAN trial, which were published in The New England Journal of Medicine in October 2023. Results from a planned interim analysis of event-free survival (EFS) showed a statistically significant and clinically meaningful 32% reduction in the risk of recurrence, progression events or death versus chemotherapy alone in patients treated with the Imfinzi-based regimen before and after surgery (32% data maturity; EFS hazard ratio of 0.68; 95% confidence interval [CI] 0.53-0.88; p=0.003902).

In a final analysis of pathologic complete response (pCR), treatment with Imfinzi plus neoadjuvant chemotherapy before surgery resulted in a pCR rate of 17.2% versus 4.3% for patients treated with neoadjuvant chemotherapy alone (difference in pCR 13.0%; 95% CI 8.7-17.6).

Each year, there are an estimated 2.4 million people diagnosed with lung cancer globally, with approximately 235,000 new diagnoses expected in the US in 2024.1-2 Around 25-30% of all patients with NSCLC, the most common form of lung cancer, are diagnosed early enough to have surgery with curative intent.3-4 However, the majority of patients with resectable disease will develop recurrence and only 36-46% of patients with Stage II disease will survive for five years.5-6 This decreases to 24% for patients with Stage IIIA disease and 9% for patients with Stage IIIB disease, reflecting a high unmet medical need.6

John V. Heymach, MD, PhD, Professor and Chair Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center in Houston, Texas, said: "This approval brings an important new treatment option that should become a backbone combination approach for patients with resectable non-small cell lung cancer, who have historically faced high rates of recurrence even after chemotherapy and surgery. When added both before and after surgery, durvalumab delivered a significant and meaningful improvement in outcomes in this curative-intent setting."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "Today’s approval of Imfinzi in resectable early-stage lung cancer builds on its strong foundation of changing clinical practice in unresectable Stage III disease. We remain committed to bringing novel approaches like AEGEAN to early lung cancer settings where cure is the goal of treatment."

Imfinzi was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery versus chemotherapy alone.

Imfinzi is also approved in the UK, Switzerland and Taiwan (China) in this setting based on the AEGEAN results. Regulatory applications are also currently under review in the EU, China and several other countries in this indication.

Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy based on the PACIFIC Phase III trial.

Notes

Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1,7 Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), with 80-85% of patients diagnosed with NSCLC.8-9

Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.10-11 The majority of patients with resectable disease eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.5

AEGEAN
AEGEAN is a randomised, double-blind, multi-centre, placebo-controlled global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage IIA-IIIB (Eighth Edition AJCC Cancer Staging Manual) NSCLC, irrespective of PD-L1 expression. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 802 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles prior to surgery, followed by Imfinzi or placebo every four weeks (for up to 12 cycles) after surgery. Patients with known EGFR or ALK genomic tumour aberrations were excluded from the primary efficacy analyses.

In the AEGEAN trial, the primary endpoints were pCR, defined as no viable tumour in the resection specimen (including lymph nodes) following neoadjuvant therapy, and EFS, defined as the time from randomisation to an event like tumour recurrence, progression precluding definitive surgery, or death. Key secondary endpoints were major pathologic response, defined as residual viable tumour of less than or equal to 10% in the resected primary tumour following neoadjuvant therapy, disease-free survival, overall survival (OS), safety and quality of life. The final pathologic response analyses were performed after all patients had the opportunity for surgery and pathology assessment per the trial protocol. The trial enrolled participants from 264 centres in more than 25 countries including in the US, Canada, Europe, South America and Asia.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy. Imfinzi in combination with chemotherapy (etoposide and either carboplatin or cisplatin) is also approved for the treatment of extensive-stage SCLC and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC.

In limited-stage SCLC, Imfinzi demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoints of OS and progression-free survival compared to placebo in patients who had not progressed following standard-of-care concurrent chemoradiotherapy in the ADRIATIC Phase III trial.

In addition to its indications in lung cancers, Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU and in combination with chemotherapy (carboplatin plus paclitaxel) followed by Imfinzi monotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient in the US.

Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, breast cancer, bladder cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours. 

Pathos Expands Pipeline With Worldwide License of Phase 2-ready Brain-penetrant, PRMT5 Inhibitor

On August 15, 2024 Pathos AI, Inc. (www.pathos.com), a biotechnology company focused on revolutionizing precision medicine in cancer by harnessing the power of machine learning to transform drug development, reported the world-wide license of PRT811, a potent, selective, and orally bioavailable brain penetrant SAM-competitive PRMT5 inhibitor from Prelude Therapeutics (Press release, Pathos AI, AUG 15, 2024, View Source [SID1234653830]).

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PRT811 (renamed P-500) was developed by Prelude Therapeutics and completed a Phase 1 trial in March 2023. The trial enrolled patients with solid tumors including high-grade glioma and uveal melanoma and has potential application in other indications with high unmet need. Out of 16 patients with high-grade glioma with isocitrate dehydrogenase mutations (IDH+) in the Phase 1 trial, two confirmed complete responses (CR) were observed. At last follow-up, 1 response is ongoing and has lasted 31.0 months while the duration of response for the second CR patient was 7.5 months. Additionally, 1 patient achieved an unconfirmed partial response (PR).

In addition, out of 23 uveal melanoma patients (10 patients with splicing factor 3B subunit 1 (SF3B1) splicing mutations and 13 without an SF3B1 mutation), one confirmed PR (duration of response of 10 months) and a second unconfirmed PR were observed, both in patients SF3B1 mutations.

In the entire safety population (N=86), the most common adverse events of any grade, with an incidence of >20% were nausea (60.5%), vomiting (46.5%) fatigue (36.0%), constipation (29.1%), and thrombocytopenia (24.4%), and were predominantly grade 1-2. The most common adverse events (grade ≥3), occurring >5% were thrombocytopenia (9.3%), anemia (9.3%), and fatigue (5.8%).

"These results from Prelude’s Phase 1 study are promising news for high-grade glioma patients and clinicians, who still have limited treatment options with chemotherapy and radiation that hasn’t changed in decades. With our AI Platform, we aim to increase the already encouraging response rate of P-500 through a novel biomarker-driven strategy, ultimately bringing this medicine to patients as efficiently as possible," said Ryan Fukushima, Pathos CEO.

"Prelude’s discovery engine has delivered a number of first- or best-in-class precision medicines including PRT811, a molecule that has shown early promise in the treatment of high-grade glioma. We are confident that Pathos AI, sharing our passion for precision medicine and commitment to serving cancer patients with high unmet need, is an ideal company to drive the development of this molecule forward for patients." said Sean Brusky, Prelude CBO. "The resources from this transaction will support advancing Prelude’s pipeline."

About P-500
P-500 (previously PRT811) is a selective, brain-penetrant small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5) that has the potential to provide clinical benefit for patients with advanced solid tumors, including high-grade glioma and uveal melanoma.

PRMT5 is an enzyme that adds methyl groups to proteins in cells using a molecule called S-adenosylmethionine (SAM) which regulates protein function and interactions. Several processes that support cancer cell growth and spread depend on PRMT5, making P-500 relevant not only to advanced high-grade glioma and uveal melanoma (in which objective responses to P-500 were observed in the Phase 1 clinical trial) but also to a number of other cancer indications. Preclinical studies have demonstrated PRMT5 inhibition can sensitize cancer cells to other treatments, expanding the application of P-500 to combination therapy in additional indications.

STADA Interim Report on the First Half of 2024

On August 15, 2024 Stada reported Interim Report on the First Half of 2024 (Presentation, Stada, AUG 15, 2024, View Source [SID1234647165]).

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LIXTE Biotechnology Holdings to Present at Two Investor Conferences

On August 15, 2024 LIXTE Biotechnology Holdings, Inc. ("LIXTE" or the "Company") (Nasdaq: LIXT and LIXTW), a clinical stage pharmaceutical company, reported it will be presenting at two investor conferences (Press release, Lixte Biotechnology, AUG 15, 2024, View Source [SID1234645984]):

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■ The Investor Summit Summer 2024 Virtual Conference Tuesday, August 20, 2024, at 2 p.m. EDT/11 a.m. PDT. To access the presentation, visit LIXTE’s investor relations website at View Source

■ The H.C. Wainwright 26th Annual Global Investor Conference, on demand starting at 7 a.m. EDT/4 a.m. PDT, September 9-11, 2024. To access the virtual presentation, register for the conference at www.hcwevents.com/annualconference.

Bas van der Baan, CEO of LIXTE, will present an overview of the Company’s clinical trials with LB-100, its proprietary compound focused on enhancing chemotherapy and immunotherapy treatments as cancer therapies. Proof-of-concept clinical trials are currently in progress for colorectal, ovarian and sarcoma cancers, including trials funded by GSK and Roche.

Nuntius Therapeutics Announces Collaboration with Taiho Pharmaceutical to Develop Next-Generation mRNA Therapies Using Nuntius’ Proprietary Cell-Specific Delivery Technology

On August 15, 2024 Nuntius Therapeutics ("Nuntius"), a biotech company developing transformative mRNA therapies through their advanced delivery technology, reported that they have entered into a collaboration agreement with Taiho Pharmaceutical Co., Ltd. ("Taiho"), a leading company in Japan for developing innovative medicines for the treatment of cancer (Press release, Nuntius Therapeutics, AUG 15, 2024, View Source [SID1234645957]). Taiho will use Nuntius’ cell-specific peptide dendrimer- and lipid-based nanocarriers to develop novel mRNA cancer immunotherapies.

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The collaboration agreement follows a successful feasibility study which evaluated Nuntius’ delivery capabilities.

"We are thrilled to embark on this collaboration with Taiho to improve treatments for cancer patients. Taiho is an excellent partner for us given their strong oncology focused research and commercial capabilities," said Benita Nagel, CEO & Co-Founder of Nuntius.

"Delivery remains a major challenge for mRNA therapies. This agreement validates our nanocarriers as an exceptionally effective cell-specific delivery technology for genetic medicines," added Albert Kwok, PhD, CSO & Co-Founder of Nuntius.

The financial terms of the collaboration agreement were not disclosed.

Nuntius’ programmable and scalable nanocarriers can effectively and safely target cell types beyond the liver and outperform leading delivery technologies. The company recently published its machine learning approach to discovering high-performing mRNA nanocarriers in the journal Advanced Science. Nuntius’ high-throughput, in silico screening of delivery vehicle candidates significantly reduces the time and cost required to bring mRNA therapies to the clinic.