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Tagrisso approved in the EU for patients
with unresectable EGFR-mutated lung cancer

On December 23, 2024 AstraZeneca reported that Tagrisso (osimertinib) has been approved in the European Union (EU) for the treatment of adult patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations and whose disease has not progressed during or following platinum-based chemoradiation therapy (CRT) (Press release, AstraZeneca, DEC 23, 2024, View Source [SID1234649256]).

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the LAURA Phase III trial, which were published in The New England Journal of Medicine.

In the trial, Tagrisso reduced the risk of disease progression or death by 84% compared to placebo (hazard ratio 0.16; 95% confidence interval 0.10-0.24; p<0.001) as assessed by blinded independent central review. Median progression-free survival (PFS) was 39.1 months in patients treated with Tagrisso versus 5.6 months for placebo.

Overall survival (OS) results remain immature, and the trial is continuing to assess OS as a secondary endpoint.

Each year in Europe, there are more than 450,000 people diagnosed with lung cancer, and approximately 80-85% have NSCLC.1-3 Among those with NSCLC in Europe, about 10-15% have tumours with an EGFR mutation.4-6

Manuel Cobo, MD, Specialist Physician of the Medical Oncology Service at the Carlos Haya University Hospital, Malaga, Spain, and investigator for the trial, said: "Today’s approval marks a major breakthrough for patients in the EU with unresectable, EGFR-mutated non-small cell lung cancer, delivering the first targeted treatment in this setting. Osimertinib reduced the risk of disease progression or death by an unprecedented 84 per cent in the LAURA trial, setting a new benchmark for outcomes and underscoring the importance of testing for EGFR mutations upon diagnosis."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "Tagrisso is now the first and only EGFR inhibitor and targeted treatment approved in the EU for locally advanced, unresectable lung cancer, providing a new standard of care to patients who have historically experienced early progression after chemoradiation therapy. The powerful results from the LAURA trial show Tagrisso improves outcomes for patients in the unresectable setting, reinforces the importance of timely EGFR testing and solidifies Tagrisso as the backbone therapy in EGFR-mutated non-small cell lung cancer."

The safety and tolerability of Tagrisso in the LAURA trial was consistent with its established profile and no new safety concerns were identified.

This is the fifth major approval for Tagrisso based on the LAURA trial following recent approvals in the US, Switzerland, South Korea and Australia. Regulatory applications are also currently under review in China, Japan and several other countries.

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

Notes

Lung cancer
Each year, an estimated 2.4 million people are diagnosed with lung cancer globally.7 Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.7 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.2,3 The majority of all NSCLC patients are diagnosed with advanced disease.8

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.4-6 Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.9

LAURA
LAURA is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial in patients with unresectable, Stage III EGFRm NSCLC whose disease has not progressed following definitive platinum-based CRT. Patients were treated with Tagrisso 80mg once-daily oral tablets until disease progression, unacceptable toxicity or other discontinuation criteria were met. Upon progression, patients in the placebo arm were offered treatment with Tagrisso.

The trial enrolled 216 patients in more than 145 centres across more than 15 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS.

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

There is an extensive body of evidence supporting the use of Tagrisso as standard of care in EGFRm NSCLC. Tagrisso improved patient outcomes in early-stage disease in the ADAURA Phase III trial, Stage III, unresectable disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial.

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

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

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Termination of a Material Definitive Agreement

On December 22, 2024, Pfizer Inc. ("Pfizer") reported that it has notified Sangamo Therapeutics, Inc. ("Sangamo") of its termination for convenience, effective April 21, 2025 (the "Termination Date"), of the Collaboration and License Agreement (the "Collaboration Agreement") by and between Pfizer and Sangamo dated May 10, 2017, pursuant to which Pfizer and Sangamo engaged in activities in furtherance of the research, development and commercialization of giroctocogene fitelparvovec, also known as SB-525, Sangamo’s gene therapy product candidate for hemophilia A (Filing, 8-K, Sangamo Therapeutics, DEC 22, 2024, View Source [SID1234649356]). Pfizer has indicated to Sangamo that the termination relates to its decision not to submit a Biologics License Application or Marketing Authorisation Application for, or pursue commercialization of, giroctocogene fitelparvovec.

Under the terms of the Collaboration Agreement, Sangamo granted Pfizer an exclusive, worldwide, royalty-bearing license, with the right to grant sublicenses, to use certain technology controlled by Sangamo for the purpose of developing, manufacturing and commercializing giroctocogene fitelparvovec and related products. Pfizer granted Sangamo a non-exclusive, worldwide, royalty free, fully paid, perpetual, irrevocable license, with the right to grant sublicenses, to use certain manufacturing technology developed under the Collaboration Agreement and controlled by Pfizer to manufacture Sangamo’s products that utilize the adeno-associated virus (AAV) delivery system. Under the Collaboration Agreement, Sangamo was responsible for conducting the Phase 1/2 clinical study and certain manufacturing activities for giroctocogene fitelparvovec, while Pfizer was responsible for subsequent worldwide development, manufacturing, marketing and commercialization of giroctocogene fitelparvovec, including the Phase 3 AFFINE clinical trial in which giroctocogene fitelparvovec met both the primary and key secondary endpoints.
Pursuant to the Collaboration Agreement, Sangamo received an upfront license fee of $70.0 million, as well as an aggregate of $55.0 million in milestone payments, and was eligible to earn from Pfizer up to $220.0 million in remaining milestone payments for giroctocogene fitelparvovec and up to $175.0 million for other products that might have been developed under the Collaboration Agreement, subject to reduction on account of payments made under certain licenses for third-party intellectual property. In addition, Pfizer agreed to pay Sangamo royalties for each licensed product potentially developed under the Collaboration Agreement at rates equal to 14% – 20% of the annual worldwide net sales of such product, subject to certain reductions.

As of the Termination Date, the Collaboration Agreement will be terminated in its entirety, all licenses and other rights granted by Sangamo to Pfizer will terminate, and Sangamo will not be entitled to any royalties from Pfizer. In addition, Pfizer will not be liable for any milestone payment under the Collaboration Agreement that accrues between now and the Termination Date. At such time, Sangamo is entitled to receive an exclusive, worldwide, royalty-bearing, sublicensable license from Pfizer to use Pfizer’s relevant intellectual property to continue developing, manufacturing and commercializing giroctocogene fitelparvovec; in return, Pfizer would be eligible to receive low single digit royalties on net sales of giroctocogene fitelparvovec and would be released from certain liabilities to the extent they exist. In addition, at Sangamo’s request and expense following the Termination Date, Pfizer is required to transition the SB-525 program back to Sangamo and provide certain transition-related services to Sangamo. If requested by Sangamo within a reasonable period of time following the notice of termination, Pfizer and Sangamo are required to meet to mutually agree upon a transition plan to effect an orderly and timely transition to Sangamo of certain development, manufacturing and commercialization activities and responsibilities with respect to SB-525.
Over the coming months, Sangamo expects to seek a new potential partner to seek regulatory approvals for and, if approved, commercialize giroctocogene fitelparvovec.

CStone Announces Submission of Clinical Trial Application in Australia for CS2009, an Innovative PD-1/VEGF/CTLA-4 Trispecific Antibody

On December 22, 2024 CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, reported the submission of clinical trial application in Australia for CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody), a leading asset from the Company’s Pipeline 2.0 to address various solid tumors (Press release, CStone Pharmaceauticals, DEC 22, 2024, View Source [SID1234649250]). This first-in-human study has also been registered and published on Clinicaltrials.gov (NCT number: NCT06741644).

CS2009 features an innovative molecular design that targets PD-1, VEGFA, and CTLA-4 simultaneously, maintaining balanced affinity for PD-1 and CTLA-4. This design enables preferential targeting of double-positive tumor-infiltrating T lymphocytes (TILs), effectively blocking both PD-1 and CTLA-4 while sparing CTLA-4 on single-positive cells. This approach could potentially reduce systemic toxicity without compromising efficacy. Additionally, CS2009 induces high and rapid internalization, leading to the down-regulation of PD-1 and CTLA-4 expression on the TIL cell membrane. Notably, CS2009 retains full VEGF inhibitory function, and preclinical data indicate that its anti-VEGF activity exhibits significant synergistic effects with its immune checkpoint inhibitory functions—crosslinking with VEGFA markedly enhances both anti-PD-1 and anti-CTLA-4 activities.

At the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC Annual Meeting) in 2024, CStone presented compelling preclinical data for CS2009, demonstrating superior anti-tumor activity compared to potential competitors. The data underscored the potential of CS2009 to address a wide range of tumor types, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, hepatocellular carcinoma, and gastric cancer. CS2009 is positioned as a potential first-in-class or best-in-class next-generation immuno-oncology backbone.

Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, stated: "We are excited to announce the timely submission of the Phase I clinical trial application for CS2009, marking another significant milestone in CStone’s Pipeline 2.0 strategy. Designed and developed in-house since 2022, CS2009 has evolved into a tri-specific antibody with a novel molecular design and robust preclinical data, holding the potential to replace current anti-PD-(L)1 therapies. Thanks to close collaboration across departments, we have rapidly advanced CS2009 to the clinical stage. The first-in-human study will soon commence in Australia, and we look forward to exploring the potential benefits CS2009 could bring to cancer patients, particularly those with low or negative PD-L1 expression who respond poorly to existing PD-(L)1 treatments."

CStone plans to initiate a multi-regional, first-in-human clinical trial for CS2009 in Australia in early 2025, followed by expansion into China and the United States.

About CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody)

CS2009 is a trispecific antibody targeting PD-1, VEGFA, and CTLA-4, with the potential to be first- or best-in-class for major tumor types. Its differentiated molecular design combines three clinically validated targets, preferentially invigorating exhausted TILs while demonstrating VEGF neutralization comparable to existing anti-VEGF antibodies. CS2009 covers a wide range of cancers, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, hepatocellular carcinoma, and gastric cancer.

In November 2024, CStone presented preclinical data for CS2009 at the 39th SITC (Free SITC Whitepaper) Annual Meeting. These results show that CS2009 exhibits superior anti-tumor activity compared to potential competitors, including PD-1/CTLA-4 bispecific antibodies, PD-1/VEGF bispecific antibodies, and PD-1/CTLA-4 combination therapies.

Termination of a Material Definitive Agreement.

On December 20, 2024, Kronos Bio, Inc. (the "Company") reported to have entered into a Transition Agreement and Mutual General Release (the "Transition Agreement") with Genentech, Inc. and F. Hoffmann-La Roche Ltd (together, "Genentech"), pursuant to which the Company and Genentech agreed to void and cancel all of the parties’ respective rights and obligations under the Collaboration and License Agreement between the parties dated January 6, 2023 (the "Collaboration Agreement") (Filing, Kronos Bio, DEC 20, 2024, View Source [SID1234649329]). Pursuant to the Transition Agreement, the Company will transfer and assign to Genentech all small molecule compounds, materials, data, and intellectual property generated by the Company in connection with the two discovery research programs ("Program Materials") conducted by the Company under the Collaboration Agreement, but excluding the Company’s proprietary drug discovery platform. The Company also granted to Genentech a perpetual, irrevocable, non-exclusive and fully paid up license under certain related intellectual property owned or controlled by the Company that is necessary or reasonably useful to exploit the Program Materials. The Transition Agreement has the effect of terminating the Collaboration Agreement, and provides for a general release of any actual or potential claims between the Company and Genentech relating thereto. In addition, the Transition Agreement cancels and voids any and all downstream payment obligations between the parties relating to or arising from the Collaboration Agreement or any programs or compounds arising thereunder. The Company has made a one-time payment in connection with the termination of the Collaboration Agreement, which is intended to support the transition of all activities under the Collaboration Agreement to Genentech.

The foregoing is a summary description of certain terms of the Transition Agreement and does not purport to be complete, and is qualified in its entirety by reference to the full text of the Transition Agreement to be filed, with confidential terms redacted, as an exhibit to the Company’s Annual Report on Form 10-K for the year ending December 31, 2024.

Foresight Diagnostics to Present at 43rd Annual J.P. Morgan Healthcare Conference

On December 20, 2024 Foresight Diagnostics, Inc. ("Foresight") a leading diagnostics company specializing in the development of ultra-sensitive minimal residual disease (MRD) detection, reported that CEO, Jake Chabon, will present at the 43rd Annual J.P. Morgan Healthcare Conference on Wednesday, January 15, 2025, at 7:30am Pacific Time (Press release, Foresight Diagnostics, DEC 20, 2024, View Source [SID1234649248]).

Foresight Diagnostics will be hosting meetings at the LifeSci Corporate Access Event from January 13-15, 2025, and will also be available for additional meetings on January 16. To schedule a meeting with the Company, please contact [email protected].