On November 14, 2023 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company") reported the publication of results from the Phase 1 study at Roswell Park Comprehensive Cancer Center in patients with metastatic triple-negative breast cancer using chemokine modulation therapy, including AIM ImmunoTech Inc.’s drug candidate Ampligen (also known as rintatolimod), interferon α-2b and celecoxib, followed by pembrolizumab (Press release, AIM ImmunoTech, NOV 14, 2023, View Source [SID1234637617]). The data were published in a manuscript titled, "Systemic Infusion of TLR3-Ligand and IFNα in Breast Cancer Patients Reprograms Local Tumor Microenvironment for Selective CTL Influx," in The Journal for ImmunoTherapy of Cancer.

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The pilot study evaluated the safety of systemic CKM composed of intravenous rintatolimod (Ampligen; selective TLR3 ligand), interferon α-2b and celecoxib, and the combination’s ability to promote local CTL influx to mTNBC lesions. Principal investigator and first author Shipra Gandhi, MD, of the Department of Medicine at Roswell Park, led the study under the scientific leadership of Pawel Kalinski, MD, PhD, senior author of the paper, Chair of Immunology and Senior Vice President for Team Science at Roswell Park. For more information about the study, please visit ClinicalTrials.gov: NCT03599453.

For more information, please visit Roswell Park’s website to read its press release titled "Novel Immunotherapy Approach at Roswell Park Shows Promise in Metastatic Triple-Negative Breast Cancer."

On November 14, 2023 Affimed N.V. (Nasdaq: AFMD) ("Affimed" or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported financial results and provided an update on clinical and corporate progress for the third quarter of 2023 (Press release, Affimed, NOV 14, 2023, View Source [SID1234637616]).

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"We initiated our phase 2 clinical study of acimtamig in combination with AlloNK and received encouraging feedback on the design of our LuminICE-203 trial from the FDA," said Dr. Adi Hoess, CEO of Affimed. "We also continued to make progress with AFM24 in combination with atezolizumab and advanced AFM28 in the dose escalation. This positions our company well to report further updates on all three clinical programs within the next few months."

Program Updates

Acimtamig (CD30/CD16A)

•
Initiated LuminICE-203, a phase 2 clinical study to investigate acimtamig in combination with Artiva’s AlloNK natural killer (NK) cells in patients with relapsed / refractory (r/r) classical Hodgkin lymphoma (HL). The study will also include a cohort of 20 r/r PTCL patients. The Company expects to report initial efficacy and safety data from the LuminICE-203 study in the first half of 2024.

•
Received encouraging feedback from FDA regarding questions for the Type C meeting: The FDA is highly engaged in supporting the progress and design of the study evaluating the combination of acimtamig and AlloNK as evidenced by the fast-track designation and Type C meeting feedback. According to written feedback for the Type C meeting, the LuminICE-203 study, designed based on the FDA’s recommendations and guidelines, could support accelerated approval, depending on the demonstrated magnitude of clinical benefit. In addition, the FDA agrees with Affimed’s approach to address the contribution of single components by adding a cohort to the study evaluating AlloNK/IL-2 only.

•
AFM13-104 abstract selected for oral presentation at the ASH (Free ASH Whitepaper) 2023 Annual Meeting. The oral presentation by Dr. Yago Nieto, M.D., Ph.D., professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson at the ASH (Free ASH Whitepaper) 2023 Annual Meeting will include data on a total of 42 r/r CD30-positive Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL) patients enrolled in the study with 36 patients treated at the recommended phase 2 dose (RP2D). All patients were heavily pretreated and refractory to their most recent line of therapy with active progressive disease at the time of enrollment. The acimtamig precomplexed NK cells treatment followed by three weekly infusions of acimtamig achieved an overall response rate (ORR) of 94.4% with a complete response rate of 72.2% at RP2D. Acimtamig in combination with NK cells continues to demonstrate a good safety and tolerability profile with no cases of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) or graft versus host disease (GVHD) of any grade. An in-depth analysis including updated EFS/OS data will be presented during Dr. Nieto’s oral presentation.

AFM24 (EGFR/CD16A)

•
On track to report data in December 2023 from the first three expansion cohorts of AFM24-102, a Phase 1/2a combination study of AFM24 in patients with advanced EGFR-expressing solid tumors. Expansion cohorts of the study enrolled patients with (1) EGFR-wildtype non-small cell lung cancer (NSCLC) (2) gastric /gastroesophageal junction adenocarcinoma and (3) a basket cohort evaluating pancreatic, hepatocellular, and biliary tract cancer. Based on the results from the AFM24 monotherapy study, a fourth expansion cohort of patients with EGFR-mutant NSCLC has been added to the AFM24-102 study and is enrolling and treating patients. Data from this cohort is expected in the first half of 2024.

•
AFM24 combination with NK cells. The Company is continuing to investigate the possibility of a combination of AFM24 with an allogeneic, off-the-shelf NK cell product.

AFM28 (CD123/CD16A)

•
AFM28 is investigated in a multi-center Phase 1 open-label, dose-escalation study (AFM28-101), in r/r AML. Dose level three was completed with no dose-limiting toxicities; completed enrollment in the fourth dose cohort.

Clinical development of AFM28 is planned as both single-agent and in combination with an allogeneic off-the-shelf NK cell product.

Partnerships and Collaborations

•
Affimed has completed its work on novel molecules for both Genentech and Roivant. Further development of these product candidates is at the discretion of the respective companies.

Planned Upcoming Milestones:

•
Follow-up data from AFM13-104 to be presented at the ASH (Free ASH Whitepaper) Annual Meeting in December 2023.

•
Initial data readout from the LuminICE-203 study planned in H1 2024.

•
Data release from the first three expansion cohorts of the Phase 1/2a study AFM24+atezolizumab combination study planned in December 2023.

•
Data from the EGFR-mutant NSCLC cohort planned in H1 2024.

•
Further progress updates from AFM28-101 dose escalation planned in H1 2024.

Third Quarter 2023 Financial Highlights

Affimed’s consolidated financial statements are prepared in accordance with International Financial Reporting Standards (IFRS) as issued by the International Accounting Standard Board (IASB). The consolidated financial statements are presented in Euros (€), the Company’s functional and presentation currency.

As of September 30, 2023 cash, cash equivalents and financial assets totaled €97.5 million compared to €190.3 million on December 31, 2022. Based on our current operating plan and assumptions, we anticipate that our cash and cash equivalents will support operations into 2025.

Net cash used in operating activities for the quarter ended September 30, 2023 was €18.2 million compared to €19.0 million for the quarter ended September 30, 2022.

Total revenue for the quarter ended September 30, 2023, was €2.0 million compared with €14.9 million for the quarter ended September 30, 2022. Revenue in 2022 and 2023 predominantly relates to the Roivant and Genentech collaborations, for which we have completed the work assigned to us under the respective collaboration agreements.

Research and development expenses for the quarter ended September 30, decreased by 17.7% from €26.1 million in 2022 to €21.5 million in 2023. The decrease is primarily due to the completion of our work under the Roivant and Genentech collaborations, together with a decline in head count and related costs after the reorganization, also resulting in a decline in the share-based payment expense which is further impacted by the decline in the underlying fair value of share options. The decline in research and development expenses have, however, been partially offset by the increase in higher expenses associated with the development of AFM13.

General and administrative expenses decreased 33.5% from €8.1 million in the quarter ended September 30, 2022 to €5.4 million in the quarter ended September 30, 2023. The decrease was due to a decline in legal, consulting and insurance expenses, as well as share-based payment expenses.

Net finance income/costs for the quarter ended September 30, 2023 decreased from income of €2.7 million in the quarter ended September 30, 2022, to income of €0.6 million in the quarter ended September 30, 2023. Finance income/costs in the three months ended September 30, 2023 primarily consisted of the interest expense incurred on the Bootstrap (formerly Silicon Valley Bank) loan, set-off by the interest earned on the financial assets, term deposits and cash balances. 2022 primarily consisted of foreign exchange gains/losses related to cash and cash equivalents denominated in U.S. dollars as a result of the change in the value of the U.S. dollar compared to the Euro.

Net loss for the quarter ended September 30, 2023, was €24.4 million, or €0.16 loss per common share compared with a net loss of €16.5 million, or €0.11 loss per common share, for the quarter ended September 30, 2022.

The weighted number of common shares outstanding for the for quarter ended September 30, 2023 was 149.3 million.

Additional information regarding these results will be included in the notes to the consolidated interim financial statements as of September 30, 2023, included in Affimed’s filings with the U.S. Securities and Exchange Commission (SEC).

Note on International Financial Reporting Standards (IFRS)

Affimed prepares and reports consolidated financial statements and financial information in accordance with IFRS as issued by the IASB. None of the financial statements were prepared in accordance with U.S. Generally Accepted Accounting Principles. Affimed maintains its books and records in Euro.

Conference Call and Webcast Information

Affimed will host a conference call and webcast on November 14, 2023, at 8:30 a.m. EST / 14:30 CET to discuss third quarter 2023 financial results and corporate developments.

The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source To access the call by phone, please use link: https://register.vevent.com/register/BId6f0cfc054b84432a7272424edf98afd, and you will be provided with dial-in details and a pin number.

Note: To avoid delays, we encourage participants to dial into the conference call 15 minutes ahead of the scheduled start time. A replay of the webcast will be accessible at the same link for 30 days following the call.

On November 14, 2023 2seventy bio, Inc. (Nasdaq: TSVT), a leading immuno-oncology cell therapy company, reported financial results and recent highlights for the third quarter ended September 30, 2023 (Press release, 2seventy bio, NOV 14, 2023, View Sourcenews-releases/news-release-details/2seventy-bio-reports-third-quarter-financial-results-and-1" target="_blank" title="View Sourcenews-releases/news-release-details/2seventy-bio-reports-third-quarter-financial-results-and-1" rel="nofollow">View Source [SID1234637615]).

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"This quarter, 2seventy completed a significant reshaping of our organization, enabling us to advance our pipeline in an efficient and more cost-effective manner. We are also supporting BMS’ efforts to return Abecma to growth through a variety of commercial and medical affairs initiatives, including adding more treatment sites and boots on the ground," said Nick Leschly, chief kairos officer. "Collectively, we believe these measures will give us the ability to continue our mission of delivering time to patients, operate within a more disciplined cost structure and deliver value for our shareholders."

SELECT COMMERCIAL AND FINANCIAL HIGHLIGHTS

Third quarter Abecma U.S. revenues, as reported by Bristol Myers Squibb (BMS), were $69 million. The decline in third quarter sales was due to increased competition from other BCMA-targeted therapies in addition to the planned manufacturing maintenance in June. The Company anticipates that competitive dynamics will continue to impact Abecma sales in the fourth quarter. Based on year-to-date results and current expectations for the fourth quarter, 2seventy bio does not expect to achieve the original revenue guidance of $470-570 million for 2023.
In order to restore growth in Abecma, BMS and 2seventy bio are focused on rapidly expanding the treating site footprint, competitively differentiating Abecma’s real-world data and safety profile, and educating on treatment sequencing and the emerging data supporting the use of Abecma before T cell engagers and antibody drug conjugates, including those targeting BCMA.
2seventy bio and BMS share equally in all profits and losses related to development, manufacturing, and commercialization of Abecma in the United States. 2seventy bio reported collaborative arrangement revenue of $0.5 million and $48.0 million for the three months and nine months ended September 30, 2023, respectively.
In September, the Company announced a restructuring of its business operations and research and development model to significantly reduce costs while supporting the execution of a prioritized plan for the long-term growth of the Company. This restructuring is expected to achieve $130+ million savings in 2024-2025 period.
The Company anticipates staying within the previously-guided net cash spend range of $180-220 million for 2023.
2seventy bio ended the third quarter of 2023 with cash, cash equivalents and marketable securities of $284.3 million. While the Company has sufficient cash to fund current planned operations for at least 12 months, we are no longer providing specific cash runway guidance.
"While Abecma performance was impacted due to the evolving competitive landscape, we and our partners at BMS believe in the long-term potential of Abecma to meaningfully impact the lives of multiple myeloma patients. We support BMS’ efforts to improve the commercial performance for the product," said Chip Baird, chief operating officer. "As we gain more visibility to the commercial trajectory for Abecma, we will continue to carefully manage our cash to preserve our financial runway."

SELECTED ABECMA DATA TO BE PRESENTED AT ASH (Free ASH Whitepaper)

Oral Presentation: Idecabtagene Vicleucel (ide-cel) Versus Standard Regimens in Patients (pts) with Triple-Class Exposed (TCE) Relapsed and Refractory Multiple Myeloma (RRMM): Updated Analysis from KarMMa-3
Presenter: Paula Rodriguez-Otero
Date & Time: Monday, December 11, 4:45pm PT

In the final progression-free survival (PFS) analysis from the Phase 3 KarMMa-3 study in patients with RRMM who received 2-4 prior regimens, significantly longer PFS was maintained with ide-cel versus standard regimens. In pts who received ide-cel (n = 225) or a standard regimen (n = 126), median PFS (95% CI) was 15.7 (12.5–18.9) vs 4.4 (3.4–5.8) months, respectively. The ide-cel safety profile was consistent with previous reports, with no parkinsonism or Guillain–Barré syndrome reported. Ide-cel continued to demonstrate durable, clinically meaningful improvements in pt-reported outcomes, including symptoms, functioning, and quality of life (QOL) vs standard regimens. Interim overall survival (OS) will be included in the presentation.

Poster Presentation: Efficacy and Safety of Idecabtagene Vicleucel (ide-cel) in Patients with Clinical High-Risk Newly Diagnosed Multiple Myeloma (MM) with an Inadequate Response to Frontline Autologous Stem Cell Transplantation (ASCT): KarMMa-2 Cohort 2c Extended Follow-up
Presenters: Madhav Dhodapkar; Melissa Alsina
Date & Time: Saturday, December 9, 5:30 – 7:30pm PT

In updated data from the KarMMa-2 cohort 2c study, ide-cel continued to demonstrate deep, durable responses in patients with an inadequate response to frontline ASCT. No new safety signals were observed with extended follow-up, and no deaths were reported. No patients who received lenalidomide maintenance post ide-cel experienced disease progression.

"The updated clinical data to be presented on Abecma reinforces the potential of this therapy to play an important role in earlier lines," said Steve Bernstein, chief medical officer. "In the extended follow-up from the KarMMa-3 study, we saw responses from some patients continue to deepen. The additional data from the KarMMa-2, cohort 2c study is supportive of our registrational KarMMa-9 study in a similar patient population which is now open and enrolling. We look forward to presenting these data at ASH (Free ASH Whitepaper) along with additional sub-analyses that reinforce the impact of Abecma on patient-reported outcomes, quality of life and clinical use."

RECENT UPDATES

MUC16 DATA PRESENTED AT SITC (Free SITC Whitepaper) – In November, 2seventy bio presented new pre-clinical data on its MUC16-targeted CAR T-cell therapy in ovarian cancer, being developed as part of our expanded collaboration with Regeneron, in a poster presentation at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). These preclinical data support the IND submission for MUC16, which is on track for end of year. The Company recently completed 270-MPH, an in-house clinical drug product manufacturing site, to more effectively support growing U.S. clinical needs. MUC16 will be the first program to be manufactured in this facility.
EXPANSION OF PARTNERSHIP WITH JW THERAPEUTICS – In September, 2seventy bio and JW Therapeutics announced their intention to expand their strategic alliance. The expansion, based on the partnership that was established last year, builds upon the companies’ translational and clinical cell therapy development platform originally designed to more rapidly explore T cell-based immunotherapy therapy products in Greater China. Specifically, the companies intend to add up to two additional candidates from the 2seventy bio portfolio, one in solid tumor indications using T-cell receptor (TCR) based technology and a second in autoimmune disease using a CAR T cell approach.
UPCOMING ANTICIPATED PIPELINE MILESTONES

Submission of an Investigational New Drug (IND) application for MUC16 program in ovarian cancer, being developed in partnership with Regeneron, anticipated by end of 2023.
Led by JW Therapeutics, initiation of an investigator-initiated study in China of 2seventy bio’s potency enhanced MAGE-A4 T cell receptor (TCR) program in solid tumors anticipated by end of 2023.
SELECT THIRD QUARTER FINANCIAL RESULTS

Total 2seventy bio revenues were $12.0 million for the three months ended September 30, 2023, compared to $13.4 million for the three months ended September 30, 2022. Total revenues were $89.7 million for the nine months ended September 30, 2023, compared to $35.3 million for the nine months ended September 30, 2022.
Research and development expenses were $51.3 million for the three months ended September 30, 2023, compared to $58.2 million for the three months ended September 30, 2022. Research and development expenses were $179.5 million for the nine months ended September 30, 2023, compared to $188.6 million for the nine months ended September 30, 2022.
Selling, general and administrative expenses were $13.0 million for the three months ended September 30, 2023, compared to $19.6 million for the three months ended September 30, 2022. Selling, general and administrative expenses were $53.2 million for the nine months ended September 30, 2023, compared to $60.7 million for the nine months ended September 30, 2022.
Net loss was $71.6 million for the three months ended September 30, 2023, compared to $67.9 million for the three months ended September 30, 2022. Net loss was $160.7 million for the nine months ended September 30, 2023, compared to $231.0 million for the nine months ended September 30, 2022.

Conference Call Information

2seventy bio will host a conference call and live webcast today, November 14, at 8:00 a.m. ET to discuss 3Q 2023 financial results and recent business highlights. To join the live conference call, please register at: https://register.vevent.com/register/BI2148ebda1eeb4055a857a3dbe4e61710. Upon registering, each participant will be provided with call details and access codes. The live webcast may be accessed by visiting the event link at: View Source A replay of the webcast may be accessed from the "News and Events" page in the Investors and Media section of the Company’s website at View Source and will be available for 30 days following the event.

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.