On June 25, 2024 Astrazeneca reported that high-level results from the ADJUVANT BR.31 Phase III trial, sponsored by the Canadian Cancer Trials Group (CCTG), showed Imfinzi (durvalumab) did not achieve statistical significance for the primary endpoint of disease-free survival (DFS) versus placebo in early-stage (IB-IIIA) non-small cell lung cancer (NSCLC) after complete tumour resection in patients whose tumours express PD-L1 on 25% or more tumour cells (Press release, AstraZeneca, JUN 25, 2024, View Source [SID1234644511]).

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​Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "We are disappointed in the ADJUVANT BR.31 results. Imfinzi has helped change the treatment landscape and achieved multiple positive Phase III trials for patients with earlier stages of lung cancer. We are committed to addressing the remaining unmet need in lung cancer through our broad development programme."

The safety profile for Imfinzi was consistent with its known safety profile, and no new safety concerns were reported. The data will be shared at a forthcoming medical meeting.

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.

Imfinzi is also being investigated as monotherapy and in combinations in several other early-stage lung cancer settings, including in medically inoperable or unresected Stage I-II NSCLC (PACIFIC-4) and unresectable, Stage III NSCLC (PACIFIC-5, 8 and 9).

Notes

Lung cancer
Each year, there are an estimated 2.4 million people diagnosed with lung cancer globally. Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1-2 Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), with 80-85% of patients diagnosed with NSCLC.3-4

The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.5-6 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.7-8

The majority of patients with resectable disease eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.9 Only around 58% of patients with Stage IB disease will survive for five years. This decreases to 36-46% for patients with Stage II and 24% for patients with Stage IIIA disease, reflecting a high unmet medical need.10

ADJUVANT BR.31
ADJUVANT BR.31 is a randomised, multi-centre, double-blind Phase III trial sponsored by CCTG evaluating Imfinzi in the adjuvant treatment of 1,415 patients with Stage IB (≥4cm), II or IIIA (Seventh Edition AJCC Cancer Staging Manual) NSCLC following complete tumour resection with or without adjuvant chemotherapy. AstraZeneca provided Imfinzi and support for the trial. Patients were randomised 2:1 to receive a 20mg/kg IV infusion of Imfinzi or placebo every four weeks for up to 48 weeks.

The trial is being conducted at 269 centres across 19 countries and regions including in Canada, the US, Australia, Europe and Asia. The primary endpoint is DFS in patients whose tumours express PD-L1 on 25% or more tumour cells and do not have known common EGFR mutations or ALK rearrangements. Key secondary endpoints include DFS in patients whose tumours express PD-L1 on 1% or more of cells and in patients regardless of PD-L1 tumour cell expression status, overall survival and safety. DFS is defined as time from randomisation to date of first recurrence, new cancer or death from any cause and is recognised as an important clinical measure by both physicians and patients.

Canadian Cancer Trials Group (CCTG)
CCTG is an academic cancer clinical trials research cooperative that runs Phase I-III trials to test anti-cancer and supportive therapies at over 85 hospitals and cancer centres across Canada. From the operations centre at Queen’s University, CCTG has supported more than 600 trials enrolling 100,000 patients from 40 countries on 6 continents through a global network of 20,000 investigators and clinical trial staff. CCTG is a national program of the Canadian Cancer Society, and their aim is to improve survival and quality of life for all people with cancer.

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 chemoradiation therapy. Imfinzi 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.

Imfinzi also demonstrated statistically significant and clinically meaningful event-free survival results in patients with resectable early-stage NSCLC based on the AEGEAN Phase III trial. Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery is approved for patients in Switzerland based on this trial.

In limited-stage SCLC, Imfinzi demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoints of OS and progression-free survival (PFS) 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, several gastrointestinal and gynaecologic cancers, and other solid tumours.

On June 25, 2024, a wholly-owned subsidiary of Kiniksa Pharmaceuticals, Ltd. (the "Company") reported to have entered into a Master Services Agreement (the "MSA") and Product Specific Agreement (the "PSA" and, together with the MSA, the "Agreement") with Samsung Biologics Co., Ltd. ("Samsung") pursuant to which Samsung will perform technology transfer, process performance qualification, manufacturing and supply services for the supply of the Company’s ARCALYST (rilonacept) drug substance (the "Product").

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Under the PSA, the Company committed to purchase process performance qualification and pre-approval inspection batches of the Product, which may be used for regulatory submissions and, pending regulatory approval, commercial sale. In addition, the Company is obligated to purchase additional batches of the Product in the five-year period of 2027 through 2031. The PSA will continue until the later of December 31, 2031 or the completion of the services thereunder, unless the PSA is terminated earlier. Prior to the expiration of the PSA, the parties have agreed to use commercially reasonable efforts to negotiate in good faith and enter into a new PSA that would govern future manufacturing and supply services for the Product.

The MSA will have an initial term of ten (10) years and shall automatically renew for terms of two (2) years each unless either party gives the other party written notice of termination at least eighteen (18) months prior to the end of the then-current MSA term, provided that the MSA will remain in effect for so long as any product specific agreement is in effect.

Either party may terminate the MSA or PSA in the event of a material breach by the other party that is not cured within 30 days’ written notice or in the event of insolvency. The parties may also terminate the PSA if a force majeure event continues for more than 180 consecutive days and the parties are unable to negotiate a mutually satisfactory solution.

The Agreement includes customary indemnification, intellectual property protection, limitation of liability, and confidentiality provisions.

The foregoing descriptions of the MSA and PSA are qualified in their entirety by reference to the MSA and PSA, redacted copies of which will be filed as exhibits to the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024.

On June 25, 2024 Astrazeneca reported positive high-level results from the NIAGARA Phase III trial showed AstraZeneca’s Imfinzi (durvalumab) in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS) and the key secondary endpoint of overall survival (OS) versus neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC) (Press release, AstraZeneca, JUN 25, 2024, View Source [SID1234644512]). Patients were treated with Imfinzi in combination with neoadjuvant chemotherapy before cystectomy (surgery to remove the bladder) followed by Imfinzi as adjuvant monotherapy.

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Approximately one in four patients with bladder cancer has evidence of the tumour invading the muscle wall of the bladder (without distant metastases), known as MIBC.1,2 In the MIBC setting, approximately 117,000 patients are treated with current standard of care.3 Standard treatment includes neoadjuvant chemotherapy and radical cystectomy.4 However, even after cystectomy, patients experience high rates of recurrence and a poor prognosis.4

Professor Thomas Powles, MD, Professor, Director of Barts Cancer Centre (QMUL), London, UK, and investigator in the trial, said: "Nearly half of patients with muscle-invasive bladder cancer who receive standard of care still experience disease recurrence or progression. These NIAGARA data show for the first time that adding durvalumab to chemotherapy before surgery followed by durvalumab extends patients’ lives."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The NIAGARA results support our strategy to move immunotherapy to the early stages of cancer treatment. This perioperative regimen with Imfinzi improved survival and reduced the rate at which patients experience disease recurrence or progression. We are eager to bring this regimen with the potential to transform the standard of care to patients as soon as possible."

Imfinzi was generally well-tolerated and no new safety concerns were observed in either the neoadjuvant or adjuvant setting. The safety profile of Imfinzi and neoadjuvant chemotherapy was consistent with the known profile of the individual medicines. The addition of Imfinzi did not increase the discontinuation rate due to adverse events and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

Notes

Muscle-invasive bladder cancer
Bladder cancer is the 9th most common cancer in the world, with more than 614,000 patients diagnosed each year.5 The most common type of bladder cancer is urothelial carcinoma, which begins in the urothelial cells of the urinary tract.6

Muscle-invasive bladder cancer, named for its growth into the muscle wall of the bladder, accounts for about a quarter of all bladder cancer cases.1,2 Approximately 50% of patients who undergo bladder removal surgery experience disease recurrence.4 Treatment options that prevent disease recurrence after surgery are critically needed.

NIAGARA
NIAGARA is a randomised, open-label, multi-centre, global Phase III trial evaluating Imfinzi as treatment for patients with MIBC before and after radical cystectomy. In the trial, 1063 patients were randomised to receive Imfinzi plus chemotherapy or chemotherapy alone prior to cystectomy, followed by Imfinzi or no further treatment after surgery.

The trial is being conducted at 192 centres across 22 countries and regions including in North America, South America, Europe, Australia and Asia. Its dual primary endpoints are EFS, defined as the time from treatment randomisation to an event like tumour recurrence or progression and pathologic complete response. Key secondary endpoints are OS and safety.

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 non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage small cell lung cancer (SCLC) and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC.

Imfinzi in combination with neoadjuvant platinum-containing chemotherapy before surgery and as adjuvant monotherapy after surgery has been approved in Switzerland for the treatment of adult patients with resectable NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

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, several gastrointestinal and gynaecologic cancers, and other solid tumours.

Imfinzi is being tested across early- and late-stage bladder cancer in various treatment combinations, including in non-muscle invasive disease (POTOMAC), patients with MIBC who are cisplatin-ineligible or refusing cisplatin (VOLGA) and locally advanced or metastatic disease (NILE).

On June 25, 2024 Manhattan BioSolutions, Inc. (MABS), an emerging biotech company developing new classes of precision biologics for the treatment of advanced cancers, and the Institute of Chemical Biology & Drug Discovery (ICB&DD) at Stony Brook University, led by University Distinguished Professor Iwao Ojima, reported to have signed a Letter of Intent (LOI) to establish a collaboration to develop next-generation antibody-drug conjugate (ADC) therapeutics for the treatment of solid tumors with high unmet medical need (Press release, Manhattan BioSolutions, JUN 25, 2024, View Source [SID1234644530]).

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The joint research program leverages the ICB&DD’s cutting-edge medicinal chemistry platforms, including novel fluorine-containing taxoid payloads with superior potency against drug-resistant cancers and a versatile tumor-targeting drug delivery system utilizing a triazine-based tripod linker. These innovative technologies, protected by patent applications filed by The Research Foundation of the State University of New York, have the potential to enhance the efficacy and selectivity of ADCs. MABS seeks to evaluate these technologies for potential use in its proprietary ADC program targeting a novel tumor-associated glycoprotein that is highly expressed across multiple aggressive solid tumor types while showing limited expression in healthy tissues.

"We are excited to collaborate with the ICB&DD to explore the potential of their innovative technologies in the context of ADC therapy," said Dr. Borys Shor, CEO of Manhattan BioSolutions. "This partnership brings together our deep experience in ADC development with the innovative taxoid platforms pioneered by Professor Ojima, creating an opportunity to address the limitations of current ADC therapies."

The MABS and ICB&DD teams will work together to design and evaluate novel ADC candidates with the goal of identifying a promising lead for advancement to preclinical development.

On June 25, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune diseases, reported a License Agreement with Cardiff University granting the Company exclusive rights to develop and commercialise anti-LAG-3 small molecules (Press release, Immutep, JUN 25, 2024, View Source [SID1234644513]).

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A number of promising compounds that block LAG-3, an immune checkpoint known to reduce the immune system’s response to fight cancer, have been identified under Immutep’s collaboration with the world-leading scientists at Cardiff University. Led by Professor Andrew Godkin of Cardiff University, Professor Andrea Brancale (now of the University of Chemistry and Technology, Prague), and Dr Frédéric Triebel, Immutep CSO, the compounds were identified by chemical library screening, molecular modelling (virtual screening) and synthetic chemistry.

Professor Andrew Godkin of Cardiff University said: "Our collaboration with Immutep has been exciting and fruitful, resulting in a number of small molecules with the potential to fight cancer by blocking the interaction between LAG-3 on T cells and MHC Class II on antigen-presenting cells. Small molecules represent the next generation of anti-LAG-3 therapies and hold tremendous promise, as they can be given to cancer patients as a convenient oral pill."

To date, over a dozen companies have initiated clinical trials investigating antagonist or "blocking" LAG-3 antibodies including Bristol Myers Squibb’s relatlimab, which was approved by the FDA in 2022 as part of a fixed dose combination with nivolumab for the treatment of metastatic melanoma. This new combination, known as Opdualag, achieved commercial sales of US$252 million and US$627 million in 2022 and 2023, respectively. Immutep’s program aims to develop an orally-available small molecule anti-LAG-3 treatment for cancer patients at a lower cost compared with the anti-LAG-3 monoclonal and bi-specific antibodies that are commercially available or under clinical development today.

Dr. Frédéric Triebel, Immutep CSO, said: "With our first-in-class MHC Class II agonist, eftilagimod alfa, entering late-stage clinical trials in oncology and IMP761, the world’s first LAG-3 agonist antibody targeting the root cause of autoimmune diseases scheduled to enter the clinic by mid-year, the team at Immutep continues to build on its pioneering leadership position in the LAG-3 therapeutic landscape with this novel program. This License Agreement harnesses many years of collaborative work with the expert team at Cardiff University and enables us to advance the most promising preclinical compounds towards the next stage of development."

A joint patent application has been filed by Immutep S.A.S. and University College Cardiff Consultants Limited (a Cardiff University affiliate) to protect the new intellectual property. The License Agreement builds on Immutep’s collaboration with Cardiff University which commenced in 2019. University College Cardiff Consultants Limited will receive an upfront payment of £25,000 and a milestone payment upon first commercial sale of a licensed product, and is eligible to receive low single-digit sales based royalties.