On November 14, 2023 Astrazeneca reported that PACIFIC-2 Phase III trial for Imfinzi (durvalumab) concurrently administered with chemoradiotherapy (CRT) did not achieve statistical significance for the primary endpoint of progression-free survival (PFS) versus CRT alone for the treatment of patients with unresectable, Stage III non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, NOV 14, 2023, View Source [SID1234637578]).

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Imfinzi sequentially administered after platinum-based CRT is the established, global standard of care for the treatment of unresectable, Stage III NSCLC based on the results of the PACIFIC Phase III trial. The PACIFIC-2 trial was initiated to evaluate concurrent Imfinzi administration with CRT, with the aim of addressing patients who progress or discontinue treatment during CRT and are therefore ineligible for the PACIFIC regimen.

Initial analysis of the safety and tolerability for Imfinzi and CRT in this patient population showed that the profiles were broadly consistent with the known profiles of these treatments, although there was an increased rate of infection observed during the concurrent treatment period in the experimental arm.

Jeffrey D. Bradley, MD, Vice Chair of Proton Therapy & Technology Development, Penn Medicine, Philadelphia and principal investigator for the trial said: "While the PACIFIC-2 trial results did not show what we hoped, the PACIFIC regimen remains the standard of care for patients with unresectable, Stage III non-small cell lung cancer. As a community, we will take insights from these results to advance future research."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Our goal with the PACIFIC-2 trial was to address a remaining unmet need for patients in this setting by introducing immunotherapy even earlier and concurrently administering Imfinzi with chemoradiotherapy. While today’s results did not reach statistical significance, we will learn from this trial and we remain committed to improving patient outcomes by expanding the benefit of immunotherapy to lung cancer patients across treatment settings."

AstraZeneca has several ongoing registrational trials focused on testing Imfinzi in early stages of lung cancer, including in resectable NSCLC (ADJUVANT BR.31), medically inoperable or unresected Stage I-II NSCLC (PACIFIC-4) and unresectable, Stage III NSCLC (PACIFIC-5, 8 and 9), and in limited-stage small-cell lung cancer (SCLC) (ADRIATIC).

Notes:

Stage III NSCLC
Each year, an estimated 2.2 million people are diagnosed with lung cancer globally.1 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 SCLC, with 80-85% classified as NSCLC, making it the most common form of lung cancer.2-3 Approximately one in three patients with NSCLC are diagnosed at Stage III (locally advanced), where the majority of tumours are unresectable (cannot be removed with surgery).4-5

Stage III NSCLC is divided into three subcategories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally.6 In contrast to Stage IV, when cancer has spread to other parts of the body (metastasised), the majority of Stage III patients are currently treated with curative intent.3,6

PACIFIC-2
The PACIFIC-2 trial was a Phase III, randomised, double-blind, placebo-controlled, multi-centre international study of Imfinzi concurrently administered with platinum-based CRT in patients with unresectable, Stage III NSCLC. In the trial, patients were randomised 2:1 to receive a 1,500mg fixed dose of Imfinzi or placebo every four weeks starting at the beginning of definitive CRT. Patients continued to receive Imfinzi or placebo as consolidation treatment after CRT until disease progression.

The trial was conducted at 88 centres across more than 20 countries involving 328 patients. The primary endpoint was PFS, and key secondary endpoints included overall survival, objective response rate and duration of response.

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 based on the PACIFIC Phase III trial results which have been confirmed in the real-world setting in the PACIFIC-R study.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial. Additionally, Imfinzi is approved in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON 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 in the US, EU, Japan and several other countries based on the TOPAZ-1 and HIMALAYA Phase III trials, respectively. Imfinzi is also approved in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 200,000 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, bladder cancer, several gastrointestinal cancers and other solid tumours.

In 2023, AstraZeneca announced positive results for several Phase III trials evaluating Imfinzi in various combinations, including in ovarian (DUO-O) and endometrial (DUO-E) cancers with Lynparza (olaparib), gastric and gastroesophageal cancer (MATTERHORN) and resectable NSCLC (AEGEAN).

On November 14, 2023 Astrazeneca reported that Imfinzi (durvalumab) has been approved in China for the 1st-line treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine and cisplatin) (Press release, AstraZeneca, NOV 14, 2023, View Source [SID1234637577]).

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The approval by China’s National Medical Products Administration (NMPA) was based on the primary results from the TOPAZ-1 Phase III trial published in the New England Journal of Medicine Evidence, as well as a prespecified exploratory analysis of an additional cohort of patients in China.

BTC is a group of rare and aggressive cancers that occur in the bile ducts (cholangiocarcinoma) and gallbladder.1,2 An estimated 211,000 new patients are diagnosed with gallbladder and biliary tract cancer each year, and nearly one in five patients diagnosed is in China.3,4 These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.5

Shukui Qin, MD, President of Nanjing Tianyinshan Hospital of China Pharmaceutical University and national leading principal investigator of the trial in China, said: "Over the past decade, there has been little progress in the treatment of advanced biliary tract cancer. However, the successful results of the TOPAZ-1 trial confirmed that durvalumab plus routine chemotherapy has statistically significant and clinically meaningful overall survival and progression-free survival benefits for these patients. This approval provides a new and better option for the treatment of these patients in China."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "With this approval for Imfinzi plus chemotherapy, physicians will now be able to offer this global standard-of-care treatment to patients in China, where nearly one in five patients with biliary tract cancer is diagnosed. This important milestone underscores our commitment to bring innovative medicines that transform survival outcomes to people across the globe living with aggressive gastrointestinal tumours such as biliary tract cancer."

In an interim analysis of the TOPAZ-1 Phase III trial, Imfinzi plus chemotherapy reduced the risk of death by 20% versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021). Median OS was 12.8 months versus 11.5 for chemotherapy. Additionally, efficacy results from a prespecified exploratory analysis in an additional cohort of TOPAZ-1 patients enrolled in China were consistent with those in the overall global trial population, showing Imfinzi plus chemotherapy reduced the risk of death by 22% versus chemotherapy alone (HR of 0.78; 95% CI, 0.51-1.18).

In the TOPAZ-1 trial, Imfinzi plus chemotherapy was generally well tolerated, with no new safety signals observed. Safety results in the cohort of Chinese patients were consistent with results in the overall global trial population.

Imfinzi plus chemotherapy is approved in the US, EU (1st-line), Japan and other countries for the treatment of adults with locally advanced or metastatic BTC. Regulatory applications are also currently under review in several other countries based on the TOPAZ-1 results.

Notes

Biliary tract cancer
BTC is a group of rare and aggressive gastrointestinal (GI) cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine).1,2

Early-stage BTC affecting the bile ducts and gallbladder often presents without clear symptoms and most new cases of BTC are therefore diagnosed at an advanced stage, when treatment options are limited and the prognosis is poor.5-7 Cholangiocarcinoma is more common in China and Southeast Asia and is on the rise in Western countries.1,5

TOPAZ-1
TOPAZ-1 was a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 patients with unresectable advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.

The primary endpoint was OS and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America and several countries in Asia including South Korea, Thailand, Japan and China.

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 also approved in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma (HCC) in the US, EU, Japan and many other countries based on the HIMALAYA Phase III trial.

In addition to its indications in gastrointestinal (GI) cancers, 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 based on the PACIFIC Phase III trial results, which have been confirmed in the real-world setting in the PACIFIC-R study.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small-cell lung cancer (SCLC) based on the CASPIAN Phase III trial. Additionally, Imfinzi is approved in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial. Imfinzi is approved in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 200,000 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, bladder cancer, several GI cancers, and other solid tumours. In 2023, AstraZeneca announced positive results for Phase III trials including combinations with Imfinzi in ovarian (DUO-O) and endometrial (DUO-E) cancers with Lynparza (olaparib), as well as in resectable NSCLC (AEGEAN) and in liver cancer eligible for embolisation (EMERALD-1). In June 2023, Imfinzi added to standard-of-care neoadjuvant chemotherapy met a key secondary endpoint of pathologic complete responses in the MATTERHORN Phase III trial.

On November 14, 2023 Starpharma (ASX: SPL, OTCQX: SPHRY) reported that it will present at the Bell Potter Healthcare Conference, a virtual investor conference that showcases Australia’s leading healthcare companies to institutional investors and Bell Potter’s retail network (Press release, Starpharma, NOV 14, 2023, View Source;mc_eid=bf52dd3418 [SID1234637576]).

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Starpharma will present an overview of the business, with a focus on recent milestones, including the positive clinical data reported for DEP cabazitaxel1 and DEP irinotecan2 in multiple cancers, as well as the positive preclinical data from the DEP radiotheranostics programs.

The Bell Potter Healthcare Conference presentation is appended.

On November 14, 2023 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported that it will present on several of its programs at the 15th Annual Protein & Antibody Engineering European Summit (PEGS Europe), which runs November 14-16 in Lisbon, Portugal (Press release, Molecular Partners, NOV 14, 2023, View Source [SID1234637575]). The presentation will focus on the multiple ways Molecular Partners has designed DARPins to activate the immune system against cancer only under certain conditions. This conditional activation is intended to focus immune attack more specifically against tumor cells and minimize damage to healthy cells, a major challenge for current oncology drugs and development efforts.

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The presentation consists of a review of several differentiated mechanisms of action that leverage the DARPin platform and conditional activation approaches/MoAs being advanced by Molecular Partners:

MP0317, a CD40 agonist, is designed to activate immune cells specifically within the tumor microenvironment by anchoring to fibroblast activation protein (FAP), which is highly expressed on tumor cells. Positive data from MP0317’s ongoing Phase 1 clinical study in patients with advanced solid tumors was recently presented at the 2023 Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper).
MP0533, a novel tetra-specific DARPin for the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (AML/MDS), engages CD3 on T cells and targets three tumor-associated antigens (TAAs) CD33, CD123, and CD70. MP0533 preferentially binds with higher avidity to cells expressing at least two of these three TAAs. This proposed MoA focuses on T cell-mediated preferential killing of AML cells while potentially sparing healthy cells. MP0533 is currently in Phase 1/2a clinical development and initial data will be presented at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.
The SWITCH-DARPin platform, a versatile novel DARPin design for conditionally triggering an immune cell attack only in the presence of defined tumor antigens.
Details of the presentation can be found below. The presentation will be made available on Molecular Partners’ website after the conference.

Title: From Clustering Activated Agonists to SWITCH-DARPins
Presenter: Dr Daniel Steiner, Senior Vice President of Research, Molecular Partners
Agenda section: Engineering: Conditionally Activated Biologics
Timing: Tuesday November 14, 2023, 11:15am GMT

In addition to the conditionally activated DARPin designs referenced above, Molecular Partners continues to progress its Radio-DARPin Therapy (RDT) platform and portfolio of projects, both in-house and in partnership with Novartis. The portfolio of RDT candidates represent a unique delivery system for radioactive payloads to solid tumors and has significantly expanded the company’s work in oncology therapeutics.

On November 14, 2023 Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized viral vector-based cancer vaccines targeting neoantigens, reported the completion of its oversubscribed Series C equity financing raising €67.5 million ($72 million) from a syndicate of renowned international healthcare investors (Press release, NousCom, NOV 14, 2023, View Source;utm_medium=rss&utm_campaign=nouscom-raises-e67-5-million-72-million-in-oversubscribed-series-c-financing-round [SID1234637571]).

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The Series C round was co-led by Andera Partners, Bpifrance (through its InnoBio 2 fund) and M Ventures, with participation from Revelation Partners, Indaco Venture Partners, Panakès Partners, XGen Ventures, and other undisclosed investors together with continued support from existing investors 5AM Ventures, EQT Life Sciences and Versant Ventures. Concurrent with the financing, representatives from Andera Partners, Bpifrance and M Ventures have joined the Nouscom Board of Directors.

The proceeds will be used to continue advancing and expanding Nouscom’s wholly owned clinical pipeline to achieve multiple clinical value catalysts, including:

Readout from Nouscom’s ongoing randomized Phase 2 clinical trial for NOUS-209, an off-the-shelf vaccine targeting 209 shared neoantigens, in combination with pembrolizumab for the treatment of Mismatch Repair/Microsatellite Instable (dMMR/MSI) Metastatic Colorectal Cancer (mCRC).
Final readout from the ongoing Phase 1b study and advancement of NOUS-209 monotherapy in Lynch Syndrome (LS) carriers investigating the potential to intercept, prevent or delay cancer before it occurs. LS carriers have a genetic predisposition to and consequently higher risk of developing certain cancers. Promising initial results from this study were reported in a Late-breaking Abstract at the recent Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2023 Annual Meeting – see press release here
Completion of a Phase 1b study evaluating NOUS-PEV, a personalized cancer immunotherapy, in combination with a checkpoint inhibitor in patients with advanced melanoma and entry into randomized Phase 2 trials in indications with high unmet medical needs.
Dr. Marina Udier, Chief Executive Officer of Nouscom, said: "This oversubscribed financing, in what is a challenging environment for all biotech companies, is testament to the faith that new and existing investors place in Nouscom and our best-in-class technology. I am constantly inspired by the relentless drive our team exhibits on a daily basis to advancing our innovative medicines for the benefit of cancer patients. This financing will allow us to further accelerate development across our wholly owned clinical portfolio reporting multiple clinical trial readouts including from our ongoing randomized Phase 2 clinical trial with NOUS-209. These Phase 2 data, if positive, have the potential to position Nouscom’s neoantigen based cancer vaccines amongst the most thrilling developments in the field."

Dr. Goran Ando, Independent Chairman of Nouscom, said: "In conjunction with the financing, I am delighted to welcome all our new investors to the company and Sofia, Thibaut and Hakan from Andera, Bpifrance and M Ventures, respectively, to our Board of Directors. Together, with the experience of our existing Board Members, I look forward to their contributions as Nouscom navigates the next exciting steps in its journey."

Dr. Sofia Ioannidou, Partner of Andera Partners, said: "We at Andera are delighted to support Marina and her team in their mission to advance the development of their innovative cancer treatments for patients. We believe that the robustness of the clinical results generated so far positions Nouscom as one of the leading biotech companies in the vibrant neoantigen cancer vaccine space. We look forward to supporting the company towards the further clinical validation of its platform."

Dr. Thibaut Roulon, Senior Investment Director at Bpifrance, said: "We consider Nouscom’s neoantigen cancer vaccine platform to be one of the most promising. It is backed by excellent science and increasingly promising clinical data. The next couple of years will be exciting as ongoing clinical trials complete and further validate its potential."

Dr. Hakan Goker, Managing Director and Head of Biotechnology Investments at M Ventures, said: "A key criteria for our investment in Nouscom was the quality of the data that have been presented over the past few years, the breadth of its pipeline, and the expertise built in the team. The emerging data positions Nouscom’s pipeline among the most exciting in the field of neoantigen based cancer vaccines creating significant value for the company. We are excited to support the company to continue bringing these innovative candidates closer to patients."