On September 18, 2020 Alkermes plc (Nasdaq: ALKS) reported that new clinical data from ARTISTRY-1, an ongoing phase 1/2 study evaluating Alkermes’ investigational engineered interleukin-2 (IL-2) variant immunotherapy, ALKS 4230, administered intravenously as monotherapy and in combination with the PD-1 inhibitor pembrolizumab (KEYTRUDA) in patients with refractory solid tumors (Press release, Alkermes, SEP 18, 2020, View Source [SID1234565340]). Data from the ongoing ARTISTRY-1 study showed encouraging single-agent activity of ALKS 4230 in melanoma and durable responses in multiple tumor types in combination with pembrolizumab. The most frequently observed treatment-emergent adverse events (AEs) in both the monotherapy and combination cohorts were transient fever and chills, consistent with anticipated effects of immunotherapy. These data are being presented in a mini oral presentation at the 2020 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress, held Sept. 18-21. The company also announced today the expansion of the ARTISTRY-1 monotherapy melanoma cohort based on achievement of protocol-defined efficacy response criteria.

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"New treatment options are needed to improve clinical outcomes in many cancer types. Current immunotherapies are not an option for all cancer types and only a portion of eligible patients respond to them," said Ulka N. Vaishampayan, M.D., Lead Investigator and Professor, Internal Medicine, Division of Hematology/Oncology, University of Michigan. "The monotherapy anti-tumor efficacy and the durable responses in the combination cohorts in multiple tumor types, including heavily pretreated platinum-resistant ovarian cancer, triple-negative breast cancer and esophageal cancer, provide additional insights into ALKS 4230’s potential as a treatment option for patients with advanced tumors that may not respond to the current standard of care."

Data highlights include:

ALKS 4230 Monotherapy
The monotherapy expansion stage of ARTISTRY-1 is evaluating the recommended phase 2 dose of ALKS 4230 (6 µg/kg/day) administered intravenously in patients with refractory melanoma or refractory renal cell carcinoma (RCC). A total of 15 patients across both monotherapy cohorts were treated, with responses observed in melanoma. (Data as of July 24, 2020 unless otherwise noted.)

Melanoma cohort
Of the 5 evaluable melanoma patients (>1 scan), one had a confirmed partial response (PR) and two had stable disease on at least two consecutive scans.
The PR was achieved in a patient with metastatic urethral melanoma by week 20 of treatment, and a deepening of response was observed through week 39 of treatment. This patient’s serum lactate dehydrogenase (LDH) levels, a known marker for treatment response in melanoma, normalized at week 5 of treatment and remained within the normal range throughout the treatment period. As of July 27, 2020, the patient had experienced a total tumor shrinkage of 39% and was continuing monotherapy treatment.
Since the July 24, 2020 data cut, one additional melanoma patient achieved a PR, awaiting a confirmatory scan. As of Sept. 1, 2020, this additional patient had experienced a total tumor shrinkage of 39% and was continuing monotherapy treatment.
With the observance of two PRs among the first 6 evaluable patients in the monotherapy melanoma cohort, the protocol-defined response criteria for expansion of this cohort was achieved, and the cohort will now enroll up to 20 additional patients for a total of up to 41 patients.
ALKS 4230 in Combination with Pembrolizumab
Data presented at ESMO (Free ESMO Whitepaper) from the combination stage of ARTISTRY-1 included data from patients in the PD-1/L1-approved, PD-1/L1-unapproved and monotherapy rollover cohorts (n=67 total). Patients representing more than 10 tumor types received ALKS 4230 3 µg/kg/day in combination with pembrolizumab. Responses were observed across multiple tumor types. (Data as of Aug. 7, 2020.)

Refractory ovarian cancer
Of the 13 evaluable patients (≥1 scan) with progressive, refractory ovarian cancer, 9 demonstrated stable disease on their first scan. Six of these 9 patients received a second scan by the data cutoff date, and 5 had stable disease or better. All 5 of these ovarian cancer patients were heavily pretreated and platinum-resistant, and each experienced tumor burden reduction with the combination of ALKS 4230 and pembrolizumab. Of these 5 patients:
One patient with platinum-resistant ovarian cancer achieved a complete response (CR) by week 45 of treatment, and a deepening of response was observed through week 81 of treatment. As of the data cut, this patient had a durable, confirmed CR and had remained on treatment for more than 18 months.
Two other patients with platinum-resistant ovarian cancer achieved PRs, one confirmed and one unconfirmed. As of the data cut, the patient with the confirmed PR demonstrated a deepening of response and had remained on treatment for more than 5 months.
Other tumor types
Additional PRs were achieved in multiple other tumor types across the PD-1/L1 approved and unapproved cohorts, including one patient with triple-negative breast cancer and two patients with esophageal cancer (one of which is awaiting confirmation). As of the data cut, these three patients had sustained PRs and continued on treatment.
Safety and Tolerability
(Data as of July 24, 2020 unless otherwise noted.)

The safety profile of ALKS 4230 in combination with pembrolizumab was generally consistent with the monotherapy profile. Based on the data available, ALKS 4230 in combination with pembrolizumab did not demonstrate any additive toxicity to that already established with pembrolizumab alone.
The most frequently observed treatment-emergent AEs in both the monotherapy and combination groups were transient fever and chills, all grade 1 or 2 in severity, which are consistent with anticipated effects of cytokine therapy. One patient in the monotherapy cohort had a grade 3 transient hypotension that was managed with fluids. There were no reports of vascular leak syndrome, which is a known AE associated with high-dose IL-2 treatment.
There were no deaths due to treatment-related AEs in the monotherapy cohorts. One death of a pancreatic cancer patient in the combination cohort, which occurred after the data cutoff, was due to inanition (starvation) and assessed as related to both study drugs.
"The data presented at ESMO (Free ESMO Whitepaper) include early evidence of ALKS 4230’s single-agent activity and its potential to deliver clinical benefit in multiple tumor types as a combination therapy," said Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President of Research & Development at Alkermes. "We’re seeing increased momentum in enrollment trends across the broader ARTISTRY clinical development program, and we look forward to presenting our accumulating data for ALKS 4230 at future medical meetings."

The mini oral presentation (#1027) titled, "ALKS 4230 Monotherapy and in Combination With Pembrolizumab in Patients With Refractory Solid Tumors (ARTISTRY-1)," is available on the ESMO (Free ESMO Whitepaper) website at www.esmo.org/meetings/esmo-virtual-congress-2020.

Conference Call and Webcast
Alkermes will host a webcast presentation and conference call with accompanying slides for analysts and investors on Friday, Sept. 18, 2020, at 8:30 a.m. ET (1:30 p.m. BST) to discuss the latest data from the ARTISTRY-1 clinical trial. The webcast will feature the lead study investigator, Dr. Ulka N. Vaishampayan, Professor of Internal Medicine, Division of Hematology/Oncology, at the University of Michigan, and members of Alkermes’ management team. The webcast player may be accessed on the Investors section of Alkermes’ website at www.alkermes.com. To participate in the question and answer session, please also dial in to the conference call, which may be accessed by dialing +1 877-407-2988 for U.S. callers and +1 201-389-0923 for international callers. In addition, a replay of the conference call may be accessed by visiting Alkermes’ website or by dialing +1 877-660-6853 for U.S. callers and +1 201-612-7415 for international callers, using replay access code 13708824. The conference call replay will be available from 11:30 a.m. ET (4:30 p.m. BST) on Friday, Sept. 18, 2020 through Friday, Sept. 25, 2020.

About ALKS 4230
ALKS 4230 is an investigational, novel, engineered fusion protein comprised of modified interleukin-2 (IL-2) and the high affinity IL-2 alpha receptor chain, designed to selectively expand tumor-killing immune cells while avoiding the activation of immunosuppressive cells by preferentially binding to the intermediate-affinity IL-2 receptor complex. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while mitigating certain limitations.

About the ARTISTRY Clinical Development Program
ARTISTRY is an Alkermes-sponsored clinical development program evaluating ALKS 4230 in patients with advanced solid tumors.

ARTISTRY-1 and ARTISTRY-2 are phase 1/2 studies evaluating the safety, tolerability, efficacy and pharmacokinetic and pharmacodynamic effects of ALKS 4230 in patients with refractory advanced solid tumors, in both monotherapy and combination settings with the PD-1 inhibitor pembrolizumab (KEYTRUDA). In ARTISTRY-1, ALKS 4230 is administered as an intravenous infusion daily for five consecutive days. In ARTISTRY-2, ALKS 4230 is administered subcutaneously and is being evaluated with once-weekly and once-every-three-week dosing schedules.

ARTISTRY-3 is a phase 2 study evaluating the clinical and immunologic effects of ALKS 4230 monotherapy administered intravenously on the tumor microenvironment of a variety of advanced, malignant solid tumors.

On September 18, 2020 AstraZeneca and MSD’s Lynparza (olaparib) demonstrated a long-term progression-free survival (PFS) benefit versus placebo as a 1st-line maintenance treatment in patients with newly diagnosed, advanced BRCA-mutated (BRCAm) ovarian cancer who had a complete or partial response following platinum-based chemotherapy (Press release, AstraZeneca, SEP 18, 2020, View Source [SID1234565339]).

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Ovarian cancer is the eighth most common cause of cancer death in women worldwide and in 2018, there were nearly 300,000 new patients diagnosed and around 185,000 deaths globally.1 Approximately 22% of patients with ovarian cancer have a BRCA1/2 mutation.2

Five-year follow-up data from the SOLO-1 Phase III trial showed Lynparza reduced the risk of disease progression or death by 67% (based on a hazard ratio [HR] of 0.33; 95% confidence interval [CI] 0.25-0.43) and improved PFS to a median of 56.0 months versus 13.8 months for placebo. At five years, 48.3% of patients treated with Lynparza remained free from disease progression versus 20.5% on placebo. The median duration of treatment with Lynparza was 24.6 months versus 13.9 months with placebo.

Susana Banerjee, one of the investigators from the SOLO-1 trial and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Reader at The Institute of Cancer Research, London, said: "For patients with newly-diagnosed BRCA-mutated advanced ovarian cancer, the benefit derived from two years of maintenance treatment with Lynparza continued long after treatment ended. After five years, almost half of women were free of cancer progression. These results represent a significant step forward in the treatment of BRCA-mutated advanced ovarian cancer."

José Baselga, Executive Vice President, Oncology R&D, said: "Once a patient’s ovarian cancer recurs, it historically has been incurable. Even at an advanced stage, we have shown that maintenance treatment with Lynparza can help patients achieve sustained remission. Today’s results further underline the critical importance of identifying a patient’s biomarker status at the time of diagnosis to offer a treatment that may help delay disease progression."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "This is the first trial of a PARP inhibitor to read out a five year follow up and showed Lynparza improved progression-free survival to over four and half years versus 13.8 months with placebo following response to 1st-line platinum-based chemotherapy. This latest data represents a major and significant milestone in a disease which has historically had such a poor prognosis."

Summary of results

summary of results
The safety profile of Lynparza was consistent with previous observations. The most common adverse events (AEs) ≥20% were nausea (77%), fatigue/asthenia (63%), vomiting (40%), anaemia (39%) and diarrhoea (34%). The most common ≥ grade 3 AEs were anaemia (22%) and neutropenia (9%). 12% of patients on Lynparza discontinued treatment due to an AE.

The results were presented on Friday 18 September during the 2020 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) virtual congress.

The SOLO-1 Phase III trial met the primary endpoint of PFS in June 2018, which formed the basis of approvals in the US, the EU, Japan, China, and several other countries.

Ovarian cancer

For newly diagnosed patients with advanced ovarian cancer, the primary aim of first-line treatment is to delay progression of the disease for as long as possible and maintain the patient’s quality of life with the intent of achieving complete remission.3-6

About SOLO-1

SOLO-1 was a Phase III, randomised, double-blinded, placebo-controlled, multi-centre trial to evaluate the efficacy and safety of Lynparza tablets (300mg twice daily) as a maintenance monotherapy compared with placebo in patients with newly-diagnosed BRCAm advanced ovarian cancer following first-line platinum-based chemotherapy. The trial randomised 391 patients with a deleterious or suspected deleterious germline or somatic BRCA1 or BRCA2 mutation who were in clinical complete or partial response following platinum-based chemotherapy.
Patients were randomised (2:1) to receive Lynparza or placebo for up to two years or until disease progression. Patients who had a partial response at two years were permitted to stay on therapy at the investigator’s discretion. The primary endpoint was PFS and key secondary endpoints included time to second disease progression or death, time to first subsequent treatment and overall survival.

Lynparza

Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in a number of countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China, and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in the US as a 1st-line maintenance treatment with bevacizumab for patients with homologous recombination deficiency (HRD)-positive advanced ovarian cancer. Lynparza is approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer. It is also approved in the US and several other countries for the treatment of germline BRCA-mutated metastatic pancreatic cancer. Lynparza is approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer. Regulatory reviews are underway in several countries for ovarian, breast, pancreatic and prostate cancers.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 30,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

The AstraZeneca and MSD strategic oncology collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and Koselugo (selumetinib), a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

On September 18, 2020 AstraZeneca reported that Updated results from the PACIFIC Phase III trial showed Imfinzi (durvalumab) demonstrated a sustained, clinically meaningful overall survival (OS) and progression-free survival (PFS) benefit in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who had not progressed following concurrent chemoradiation therapy (CRT) (Press release, AstraZeneca, SEP 18, 2020, View Source [SID1234565338]).

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One in three patients with NSCLC are diagnosed at Stage III, where the majority of tumours are unresectable (cannot be removed with surgery).1,2 Prior to the approval of Imfinzi in this setting, no new treatments beyond CRT had been available to these patients for decades.3,4,5

The results from the updated post-hoc analyses showed an estimated four-year overall survival rate of 49.6% for Imfinzi versus 36.3% for placebo after CRT. Median OS was 47.5 months for Imfinzi versus 29.1 for placebo. With a maximum treatment course of one year, an estimated 35.3% of patients treated with Imfinzi had not progressed four years after enrolment versus 19.5% for placebo. These data build on The New England Journal of Medicine publication from 2018 demonstrating a significant benefit for Imfinzi in the OS primary endpoint.6

Corinne Faivre-Finn, Professor at The University of Manchester and The Christie NHS Foundation Trust, and a lead investigator in the PACIFIC Phase III trial, said: "Previously, only 15 to 30 per cent of patients with unresectable, Stage III non-small cell lung cancer survived five years, and the majority eventually progressed to metastatic disease. These data show about half of patients treated with Imfinzi survived four years, and an estimated 35 per cent had not progressed, a remarkable advance in this curative-intent setting."

José Baselga, Executive Vice President, Oncology R&D, said: "These unprecedented four-year results reinforce Imfinzi as the established standard of care in unresectable, Stage III non-small cell lung cancer and set a new survival benchmark in a setting where cure is the treatment goal. With data also at ESMO (Free ESMO Whitepaper) for CASPIAN in small cell lung cancer patients, Imfinzi continues to deliver impressive long-term benefits across different types of lung cancer."

In the primary OS analysis of the PACIFIC Phase III trial, the most common adverse events (AE) (greater than or equal to 20%) among patients treated with Imfinzi versus placebo were cough (35.2% versus 25.2%), fatigue (24.0% versus 20.5%), dyspnoea (22.3% versus 23.9%) and radiation pneumonitis (20.2% versus 15.8%). A grade 3 or 4 AE was experienced by 30.5% of patients treated with Imfinzi versus 26.1% for placebo, and 15.4% of patients discontinued treatment due to AEs with Imfinzi versus 9.8% for placebo.

CASPIAN Phase III trial exploratory subgroup analyses in extensive-stage small cell lung cancer (ES-SCLC) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020

New exploratory subgroup analyses from the CASPIAN Phase III trial of Imfinzi were conducted to characterise patients deriving long-term benefit. More than three times as many patients treated with Imfinzi plus chemotherapy were alive and progression free for one year or more (PFS ≥12 months) versus chemotherapy alone (17% versus 4.5%). Across all treatment arms, the subgroup of patients who were progression free at one year had a 75% chance of being alive at two years. In comparison, the subgroup of patients whose disease had progressed within one year (PFS <12 months) had a 10% chance of being alive at two years. Clinical characteristics did not appear to identify patients who derived long-term benefit.

Patients with PFS ≥12 months received more cycles of Imfinzi treatment compared to patients with PFS <12 months (median of 25 cycles versus 7). Although patients with greater exposure to Imfinzi had numerically higher rates of immune-mediated AEs, the two subgroups had similar rates of severe AEs, serious AEs and AEs leading to discontinuation.

The CASPIAN trial met the primary endpoint of OS in 2019, reducing the risk of death by 27% in patients with ES-SCLC treated with Imfinzi plus a choice of chemotherapy versus chemotherapy alone. The safety and tolerability of Imfinzi plus chemotherapy were consistent with the known safety profiles of these medicines. These results were published in The Lancet in 2019 and formed the basis of regulatory approvals around the world.7

Results from the PACIFIC and CASPIAN Phase III trials were presented during the ESMO (Free ESMO Whitepaper) Virtual Congress 2020, 19 to 21 September.

Lung cancer

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one fifth of all cancer deaths.8 Lung cancer is broadly split into NSCLC and SCLC, with about 85% classified as NSCLC and 15% classified as SCLC.9

Stage III NSCLC (locally advanced) is commonly divided into three sub-categories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery.10 Stage III disease is different from Stage IV disease, when the cancer has spread (metastasised), as the majority of Stage III patients are treated with curative intent.10,11 In 2015, Stage III NSCLC was estimated to affect nearly 200,000 patients in the following eight key countries: China, France, Germany, Italy, Japan, Spain, UK, and the US, with approximately 43,000 cases in the US alone.2

SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly, despite initial response to chemotherapy.12,13 About two thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body.14 Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.14

PACIFIC

The PACIFIC trial was a Phase III, randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in ‘all-comer’ patients (regardless of PD-L1 status) with unresectable, Stage III NSCLC whose disease had not progressed following concurrent platinum-based CRT.

The trial was conducted at 235 centres across 26 countries involving 713 patients. The primary endpoints of the trial were PFS and OS, and secondary endpoints included landmark PFS and OS, objective response rate and duration of response.

CASPIAN

CASPIAN was a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC. The trial compared Imfinzi in combination with etoposide and either carboplatin or cisplatin chemotherapy, or Imfinzi and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone. In the experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation.

The trial was conducted in more than 200 centres across 23 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms. In June 2019, AstraZeneca announced the CASPIAN trial had met one primary endpoint of demonstrating OS for Imfinzi plus chemotherapy at a planned interim analysis. In March 2020, it was announced that the second experimental arm with tremelimumab did not meet its primary endpoint of OS.

Imfinzi

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

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on the PACIFIC Phase III trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and several other countries. Additionally, it is approved in the US, the EU, Japan and other countries for ES-SCLC.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combinations including with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer, endometrial cancer and other solid tumours.

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

An extensive Immuno-Oncology development programme focuses on lung cancer patients without a targetable genetic mutation which represent up to three-quarters of all patients with lung cancer.15 Imfinzi, an anti-PDL1 antibody, is in development for patients with advanced disease (POSEIDON and PEARL Phase III trials) and for patients in earlier stages of disease including potentially curative settings (MERMAID-1, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC Phase III trials) both as monotherapy and in combination with tremelimumab and/or chemotherapy.

Imfinzi is also in development in the NeoCOAST, COAST and HUDSON Phase II trials in combination with potential new medicines from the early-stage pipeline including Enhertu.

AstraZeneca’s approach to Immuno-Oncology

Immuno-oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZeneca’s Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

On September 18, 2020 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported that CEO Richard Godfrey will be presenting at the Sachs Annual Biotech in Europe Forum (Press release, BerGenBio, SEP 18, 2020, View Source [SID1234565337]).

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Date and time: Wednesday 23 September at 1pm CET.

Register for the event here: View Source

The presentation will be made available on the Company website in the Presentations section on the day.

www.bergenbio.com/investors/presentations/

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL expression defines a very poor prognosis subgroup in most cancers. AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.

On September 18, 2020 Ipsen (Euronext: IPN; ADR: IPSEY) reported the release of first efficacy and safety data from the CLARINET FORTE study, with the abstract to be presented as a mini-oral presentation at the 2020 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place virtually from 19-21 September 2020 (Press release, Ipsen, SEP 18, 2020, View Source [SID1234565336]). The prospective single-arm, open-label, exploratory, international Phase II study investigated the efficacy and safety of increasing the dose frequency of Somatuline Autogel (lanreotide) in patients with pancreatic or midgut NETs with centrally-assessed progression within the last two years while on a standard lanreotide regimen for ≥24 weeks. An extension of progression-free survival (PFS) rates and encouraging disease-control rates (DCR) were recorded in both tumor types, with no new safety signals.

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"These results support a clinically meaningful benefit to a population of patients with high unmet medical need by potentially delaying escalation to more toxic treatments. This means patients with progressive NETs are able to remain on a more tolerable first-line standard of care for longer," said Professor Marianne Pavel, Friedrich-Alexander University of Erlangen, Germany, Senior Physician and Chair of Endocrinology, and lead investigator of the study.

Lanreotide is a synthetic form of a natural hormone called somatostatin and is used to control and treat the growth of some advanced tumors of the midgut and the pancreas called gastroenteropancreatic NETs or GEP-NETs. Previous studies have shown efficacy in tumor control for the 28-day regimen of lanreotide 120 mg, and positive effects on relief of clinical symptoms.2

Currently, patients with progressive disease after treatment with lanreotide (120 mg every 28 days) have limited treatment options and receive less well-tolerated systemic chemotherapy or molecular targeted therapies. As lanreotide has a favorable tolerability profile, an increased dosing frequency might delay the need for such therapies and could potentially maintain patients’ quality of life for longer.

The CLARINET FORTE study found that increasing the dose frequency of lanreotide from a first line standard dose of 120 mg every 28 days, to an increased dose of 120 mg every 14 days, a median PFS of 8.3 months (95% confidence interval [CI]: 5.5–8.3) was achieved in patients with progressive midgut NETs (n=51) and 5.6 months (95% CI: 5.5–8.3) in patients with progressive pancreatic NETs (n=48). Post-hoc subgroup analysis in the pancreatic NETs cohort showed median PFS of 8.0 months (95% CI: 5.6–8.3) in patients with Ki67 ≤10% (n=43).

"The CLARINET FORTE study is another example of Ipsen’s commitment to delivering scientific and medical advances that translate into patient outcomes. Progressive pancreatic or midgut NETs are among the fastest growing class of cancers worldwide, so we are delighted that these data presented at ESMO (Free ESMO Whitepaper) may mean that for these patients, the need for aggressive second-line therapies could be delayed for longer whilst also benefitting from continued progression-free survival," said Professor Steven Hildemann, Executive Vice President, Chief Medical Officer, Head of Global Medical Affairs and Patient Safety, Ipsen.

The study found no new safety signals associated with this increased dose regimen. The increased lanreotide dosing frequency was well-tolerated, with treatment-related adverse events (TRAEs) remaining consistent with previous clinical studies and occurring in 37.5% and 51.0% of patients in the pancreatic NETs and midgut NETs cohorts, respectively; only one TRAE was Grade ≥3 (pancreatic NETs: fatigue [n=1], Grade 3). The most common (≥10%) classes of TRAEs were gastrointestinal disorders (pancreatic NETs, 25.0%; midgut NETs, 37.3%) and general disorders/administration-site conditions (midgut NETs, 13.7%).

Together, these efficacy and safety results may represent an important therapeutic approach for patients living with pancreatic or midgut NETs. The full data will be presented as an on-demand mini-oral presentation on Friday 18 September at the ESMO (Free ESMO Whitepaper) Virtual Congress 2020.

To complement the format of the ESMO (Free ESMO Whitepaper) Virtual Congress 2020, Ipsen’s new virtual congress platform includes a virtual press office View Source to support media in accessing further information. Highlights include insights around our data and contributions to the ESMO (Free ESMO Whitepaper) 2020 scientific program, our mission to advance oncology research and our commitment to address patients’ unmet needs. Registration for a digital media briefing for selected ESMO (Free ESMO Whitepaper) data is available here.

Follow Ipsen on Twitter via @IpsenGroup and keep up to date with ESMO (Free ESMO Whitepaper) Virtual Congress 2020 news and updates by using the hashtag #ESMO20.

About NETs

Neuroendocrine tumors, or NETs, are a group of uncommon tumors that develop in the cells of the neuroendocrine system, throughout the body.3,4 NETs occur in both men and women, in general aged 50 to 60 years old, although they can affect anyone of any age.1

The three main areas where NETs are found in the body are the gastrointestinal tract, the pancreas and the lungs.3,5

Gastrointestinal NETs are found in the gastrointestinal tract or digestive system and are the most common type of NETs.5
Pancreatic NETs are formed in the islet cells of the pancreas and include several uncommon types of NETs.5
Lung NETs are less common, accounting for about one quarter of NETs.5
The symptoms of NETs are often not distinct and difficult to identify, and can take between five to seven years to fully diagnose.6 The number of people being newly diagnosed with NETs overall is believed to be rising.1 This is mainly due to increased awareness of the condition and diagnostic testing.1 NETs are now among the fastest growing class of cancers worldwide, accounting for around 2% of all cancers.1

About CLARINET FORTE

CLARINET FORTE is a prospective single-arm, open-label, exploratory, international Phase II study to explore the efficacy and safety of an increased Somatuline Autogel (lanreotide) dosing interval (120 mg every 14 days) in patients with metastatic or locally advanced unresectable pancreatic NETs or midgut NETs, with centrally-accessed progression within the last two years while on a standard lanreotide regimen (120 mg every 28 days) for more than 24 weeks.7
About Somatuline (lanreotide)

Somatuline Autogel/Depot is made of the active substance lanreotide, which is a long-acting somatostatin analogue that inhibits the secretion of growth hormone and certain hormones secreted by the digestive system. The main indications of lanreotide are: 8

The treatment of individuals with acromegaly when the circulating levels of Growth Hormone (GH) and/or Insulin-like Growth Factor-1 (IGF-1) remain abnormal after surgery and/or radiotherapy, or in patients who otherwise require medical treatment.
The treatment of grade 1 and a subset of grade 2 (Ki-67 index up to 10%) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) of midgut, pancreatic or unknown origin where hindgut sites of origin have been excluded, in adult patients with unresectable locally advanced or metastatic disease.
The treatment of symptoms associated with neuroendocrine (particularly carcinoid) tumors.
The detailed recommendations for the use of lanreotide are described in the Summary of Product Characteristics (SmPC), available here.