On December 23, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the European Commission (EC) has approved Opdivo (nivolumab) plus Yervoy (ipilimumab) for the first-line treatment of adult patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (mCRC) (Press release, Bristol-Myers Squibb, DEC 23, 2024, View Source [SID1234649259]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Colorectal cancer is the second leading cause of cancer death in Europe and patients are in need of new treatment options that delay disease progression. Approximately 5-7% of metastatic colorectal cancer patients have MSI-H/dMMR tumors and these patients are less likely to benefit from conventional chemotherapy and typically have poor prognosis outcomes," said Dana Walker, M.D., M.S.C.E., vice president, Opdivo global program lead, Bristol Myers Squibb. "The EC’s decision to approve Opdivo plus Yervoy represents a significant milestone for this patient population in the European Union and underscores our commitment to advancing treatment options."

The decision is based on results from the CheckMate -8HW trial, which were presented at medical congresses earlier this year. These data formed the basis for the Company’s application to the European Medicines Agency (EMA). In the study, Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoint of progression-free survival (PFS) and reduced the risk of disease progression or death by 79% compared to the investigator’s choice of chemotherapy as assessed by Blinded Independent Central Review (BICR). The safety profile for the dual immunotherapy combination remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified.

This approval by the EC for Opdivo plus Yervoy for the first-line treatment of adult patients with MSI-H or dMMR unresectable or mCRC is valid in all 27 member states of the European Union (EU), as well as Iceland, Liechtenstein and Norway. In addition to approval in colorectal cancer, Opdivo- based options are also approved for treatment of multiple tumor types in the EU.

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -8HW clinical trial.

CheckMate -8HW and Select Efficacy and Safety Results

With a median follow-up of approximately 31.5 months, CheckMate -8HW trial results showed:

PFS (progression-free survival; a dual primary endpoint): Opdivo plus Yervoy reduced the risk of disease progression or death by 79%. Median PFS was not yet reached in the Opdivo plus Yervoy arm (95% CI: 38.4-NE) vs. 5.9 months in the chemotherapy arm (95% CI: 4.4-7.8). Consistent PFS benefit was observed across all pre-specified subgroups, including patients with KRAS or NRAS mutations, and those with baseline liver, lung, or peritoneal metastases.
Safety: The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 23% of patients in the Opdivo plus Yervoy arm and 48% of patients in the chemotherapy arm. Any grade TRAE-related discontinuation was 17% in the Opdivo plus Yervoy arm and 32% in the chemotherapy arm.
About CheckMate -8HW

CheckMate -8HW (NCT04008030) is a Phase 3 randomized, open-label trial evaluating Opdivo plus Yervoy compared to Opdivo alone or the investigator’s choice of chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) in patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (mCRC).

839 patients were randomized to receive either Opdivo monotherapy ( Opdivo 240 mg Q2W for six doses, followed by Opdivo 480 mg Q4W), Opdivo plus Yervoy (Opdivo 240 mg plus Yervoy 1 mg/kg Q3W for four doses, followed by Opdivo 480 mg Q4W ), or investigator’s choice of chemotherapy. The dual primary endpoints of the trial are progression-free survival (PFS) per blinded independent central review (BICR) for Opdivo plus Yervoy compared to investigator’s choice of chemotherapy in the first-line setting and PFS per BICR for Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy. Further data disclosure is planned at The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium taking place January 23, 2025, through January 25, 2025. The trial also evaluates several secondary safety and efficacy endpoints, including overall survival, which is ongoing.

About dMMR or MSI-H Colorectal Cancer

Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease; it is the second leading cause of cancer-related deaths among men and women combined.

Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5-7% of metastatic CRC patients have dMMR or MSI-H tumors. These patients are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.

On December 23, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company that intends to change its name to BeOne Medicines Ltd., reported it will change its Nasdaq ticker symbol to "ONC" on January 2, 2025, reflecting its long-standing commitment to delivering innovative oncology medicines globally (Press release, BeiGene, DEC 23, 2024, View Source [SID1234649257]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"As we enter our 15th year, changing our ticker to ONC reflects our unwavering commitment to leadership in oncology and mission to deliver transformative medicines to cancer patients worldwide," said John V. Oyler, Co-Founder, Chairman and CEO at BeiGene. "This milestone inspires pride in all we have accomplished and fuels our excitement for the future as we advance our innovative hematology franchise and solid tumor pipeline, driving meaningful impact for patients everywhere."

The Company’s CUSIP number will remain unchanged. In addition, the Company stock codes and stock names for The Stock Exchange of Hong Kong and the STAR Market of the Shanghai Stock Exchange will not change. No action by the Company’s shareholders is required to implement the Nasdaq ticker symbol change.

The Company will participate in the 43rd Annual J.P. Morgan Healthcare Conference on Monday, January 13, 2025, with a presentation at 1:30 pm PT. The live webcast of the event can be accessed from the Investors section of the Company’s website at View Source, View Source, View Source An archived replay will be available for 30 days following the event.

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

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).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.