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 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 AstraZeneca reported that Tagrisso (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy has been approved in Japan for the 1st-line treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose tumours have exon 19 deletions or exon 21 (L858R) mutations (Press release, AstraZeneca, JUN 25, 2024, View Source [SID1234644510]).

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The approval by the Japanese Pharmaceuticals and Medical Device Agency (PMDA) was based on the results from the FLAURA2 Phase III trial, which were also published in The New England Journal of Medicine.

Results showed Tagrisso with the addition of chemotherapy reduced the risk of disease progression or death by 38% by investigator assessment compared to Tagrisso monotherapy, which is the 1st-line global standard of care (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). Median progression-free survival (PFS) was 25.5 months for patients treated with Tagrisso plus chemotherapy, an 8.8-month improvement versus Tagrisso monotherapy (16.7 months).

PFS results by blinded independent central review were consistent with results by investigator assessment, showing 29.4 months median PFS with Tagrisso plus chemotherapy, a 9.5-month improvement over Tagrisso monotherapy (19.9 months) (HR 0.62; 95% CI 0.48-0.80; p=0.0002).

While the overall survival (OS) remained immature at the second interim analysis (41% maturity), an encouraging trend towards an OS benefit was observed with Tagrisso plus chemotherapy versus Tagrisso alone (HR 0.75; 95% CI 0.57-0.97), presented at the 2024 European Lung Cancer Congress (ELCC) in Prague, Czech Republic (abstract #4O). The trial continues to assess OS as a key secondary endpoint.

Lung cancer is the most common cause of cancer-related deaths both globally and in Japan.1-2 Lung cancer is the second most prevalent cancer type in Japan with more than 135,000 patients diagnosed each year.2 Among those with NSCLC, the most common form of lung cancer, approximately 36% of patients in Japan have tumours with an EGFR mutation.3 Additionally, the majority of patients with NSCLC are diagnosed with advanced disease.4

Kunihiko Kobayashi, MD, PhD, Professor at Saitama Medical University International Medical Center and a principal investigator in the trial, said: "The FLAURA2 results showed osimertinib with the addition of chemotherapy provided a nearly nine-month improvement in progression-free survival versus osimertinib monotherapy. This approval brings an important new treatment option for this aggressive form of lung cancer, the leading cause of cancer death in Japan."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "Today’s approval in Japan solidifies Tagrisso as the backbone therapy for patients with EGFR-mutated lung cancer either in combination with chemotherapy or as monotherapy, now providing two effective first-line treatment options. The opportunity to combine Tagrisso with chemotherapy is especially important for those patients with a poorer prognosis, such as those whose disease has spread to the brain or those with L858R mutations."

The safety profile of Tagrisso plus chemotherapy was consistent with the established profiles of the individual medicines. Adverse event (AE) rates were higher in the Tagrisso plus chemotherapy arm, driven by well-characterised chemotherapy-related AEs. Discontinuation rates of Tagrisso due to AEs were 11% for Tagrisso plus chemotherapy and 6% for monotherapy.

Tagrisso is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage EGFRm NSCLC. Tagrisso with the addition of chemotherapy is also approved in the US and several other countries for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

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 Lung cancer is broadly split into NSCLC and small cell lung cancer.1 Each year there are an estimated 2.4 million people diagnosed with lung cancer globally, with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.4-6

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.7-9 Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.10

FLAURA2
FLAURA2 is a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso 80mg once-daily oral tablets with the addition of chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks.

The trial enrolled 557 patients in more than 150 centres across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.

There is an extensive body of evidence supporting the use of Tagrisso in EGFRm NSCLC. Tagrisso is the only targeted therapy to improve patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA Phase III trial and FLAURA2 Phase III trial.

As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the neoadjuvant setting in the NeoADAURA Phase III trial with results expected later this year and in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

The Company is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test Tagrisso plus savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.

On June 24, 2024 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE), reported that the Company has entered into a commercial and revenue sharing agreement with leading global cancer center (Press release, OSE Immunotherapeutics, JUN 24, 2024, View Source [SID1234646936]).

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This exclusive and worldwide agreement with Memorial Sloan Kettering Cancer Center (MSK) covers OSE Immunotherapeutics’ patent rights and jointly owned OSE/MSK patent rights in the field of Chimeric Antigen Receptor (CAR) cell therapy for the treatment of Interleukin-7 Receptor (IL-7R) expressing cancers, in particular hematological tumors such as Acute Lymphoblastic Leukemia. As part of this agreement, MSK will lead the research, development, and commercialization efforts, and subsequently share potential future revenues with OSE Immunotherapeutics.

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, said: "We are very pleased to reinforce our collaboration with one of the world’s most renowned US cancer hospitals in oncology and in particular in the field of CAR-T cell therapies. Based on their pioneering expertise in this area, we look forward to the clinical exploration of a potential breakthrough therapy option for IL-7R expressing cancer patients".

"I am excited for the next steps in translation of IL-7R targeted CARs to clinical trials treating IL-7R expressing tumor bearing patients at MSK," said Prasad S. Adusumilli, MD, FACS, Deputy Chief and Attending, Thoracic Service, and Vice Chair for Translational Research, Department of Surgery, at MSK. Dr. Adusumilli holds the Min H. & Yu-Fan C. Kao Chair in Thoracic Cancer at MSK. His laboratory team investigated and developed therapeutic strategies using IL-7R CAR T cells.

This new agreement is based on the initial multi-year research collaboration between MSK and OSE Immunotherapeutics to explore the preclinical potential of a non-antagonist IL-7R monoclonal antibody directed against the alpha chain of IL-7R used either as a therapeutic antibody or for the design of innovative CAR-T cells for cancer indications expressing high level of IL-7R.

On June 24, 2024 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE), reported that the Company has entered into a commercial and revenue sharing agreement with leading global cancer center (Press release, OSE Immunotherapeutics, JUN 24, 2024, View Source [SID1234646936]).

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This exclusive and worldwide agreement with Memorial Sloan Kettering Cancer Center (MSK) covers OSE Immunotherapeutics’ patent rights and jointly owned OSE/MSK patent rights in the field of Chimeric Antigen Receptor (CAR) cell therapy for the treatment of Interleukin-7 Receptor (IL-7R) expressing cancers, in particular hematological tumors such as Acute Lymphoblastic Leukemia. As part of this agreement, MSK will lead the research, development, and commercialization efforts, and subsequently share potential future revenues with OSE Immunotherapeutics.

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, said: "We are very pleased to reinforce our collaboration with one of the world’s most renowned US cancer hospitals in oncology and in particular in the field of CAR-T cell therapies. Based on their pioneering expertise in this area, we look forward to the clinical exploration of a potential breakthrough therapy option for IL-7R expressing cancer patients".

"I am excited for the next steps in translation of IL-7R targeted CARs to clinical trials treating IL-7R expressing tumor bearing patients at MSK," said Prasad S. Adusumilli, MD, FACS, Deputy Chief and Attending, Thoracic Service, and Vice Chair for Translational Research, Department of Surgery, at MSK. Dr. Adusumilli holds the Min H. & Yu-Fan C. Kao Chair in Thoracic Cancer at MSK. His laboratory team investigated and developed therapeutic strategies using IL-7R CAR T cells.

This new agreement is based on the initial multi-year research collaboration between MSK and OSE Immunotherapeutics to explore the preclinical potential of a non-antagonist IL-7R monoclonal antibody directed against the alpha chain of IL-7R used either as a therapeutic antibody or for the design of innovative CAR-T cells for cancer indications expressing high level of IL-7R.