Endocrine regulation and metabolic mechanisms of osteopontin in the development and progression of osteosarcoma, metastasis and prognosis

FDA Grants Breakthrough Therapy Status To Gilead's Trodelvy For Treatment Of Small Cell Lung Cancer

(RTTNews) - Gilead Sciences, Inc. (GILD) Tuesday said that the U.S. Food and Drug Administration or FDA has granted Breakthrough Therapy Designation to Trodelvy for the treatment of adults with extensive-stage small cell lung cancer (ES-SCLC).

The Breakthrough Therapy Designation is based on encouraging results from the Phase 2 TROPiCS-03 study of Trodelvy as a second-line treatment for ES-SCLC.

Trodelvy is currently approved in more than 40 countries for multiple types of breast cancer. The drug is also approved for the treatment of urothelial cancer in many countries.

Small Cell Lung Cancer: Navigating The Global Clinical Trial Landscape

Small cell lung cancer is a fast-growing and aggressive subtype of lung cancer, accounting for approximately 10-15% of all lung cancer cases globally. Small cell lung cancer is divided into limited-stage and extensive-stage based on disease spread. Its aggressive nature causes early metastasis to organs like the liver, bones, brain, and adrenal glands, leading to poor prognosis.

The five-year survival rate is less than 5% for extensive-stage and 15-25% for limited-stage. Small cell lung cancer is primarily caused by long-term tobacco exposure, leading to mutations in genes such as TP53 and RB1, resulting in rapid tumor growth. Symptoms include persistent cough, chest pain, and paraneoplastic syndromes. Globally, small cell lung cancer continues to pose a significant health burden, with an estimated 400,000 new cases documented. Asia reported the highest number of cases, followed by Europe, North America, and the rest of the world, highlighting the regional variation in its epidemiology.

The latest insight

According to a new report by leading global clinical contract research organisation Novotech, the treatment landscape for small cell lung cancer varies by stage and treatment history. First-line therapies for limited-stage small cell lung cancer patients include platinum-based chemotherapy with radiotherapy, as recommended by NCCN, ESMO, and recent Chinese guidelines. Extensive-stage small cell lung cancer is treated with platinum-based chemotherapy plus immunotherapy, followed by maintenance. For relapsed or refractory cases, treatment options include lurbinectedin, topotecan, or clinical trials. These guidelines offer tailored approaches to improve outcomes in small cell lung cancer.

The report, released last month, highlights how the biotech and biopharma industry has initiated around 1,200 small-cell lung cancer trial studies since 2019. Asia-Pacific is leading in the number of clinical trials conducted, followed by North America, Europe, and the rest of the world. Mainland China is prominent in the Asia-Pacific region, while the United States leads in North America. Spain and France play key roles in small cell lung cancer trials in Europe and Israel contributes moderately to the rest of the world's trials. In terms of patient recruitment trends, the United States and the Asia-Pacific region show similar recruitment rates.

Advancements in treatment

Shifting focus to the current landscape of marketed and pipeline drugs for small cell lung cancer, immune checkpoint inhibitors like pembrolizumab and nivolumab, which target PD-1/PD-L1, are key treatment options. Small molecules such as topotecan and lurbinectedin also play an important role. Promising results are emerging from phase III trials for immunotherapies like nivolumab and serplulimab. Innovative therapies, such as antibody-drug conjugates like ifinatamab deruxtecan, are also contributing to advances in small cell lung cancer treatment.

Advancements in small cell lung cancer treatment are increasingly focused on personalised approaches, with immune checkpoint inhibitors, PARP inhibitors, and antibody-drug conjugates playing key roles. Major companies, including Roche, Merck & Co., and Bristol Myers Squibb, are developing advanced therapies targeting distinct molecular subtypes. These strategies are transforming the treatment landscape, offering new hope for relapsed and refractory cases. While some aspects of small cell lung cancer biology remain unclear, ongoing research is continuously refining targeted treatments, improving outcomes for patients.

Expert support

Novotech has partnered with numerous biotech and small to mid-size companies and completed hundreds of oncology projects, including those in immuno-oncology and advanced therapies for indications such as small cell lung cancer. It supports over 5,000 clinical projects across all phases and bioequivalence studies. Recognised for its contributions,

Recognised for its industry-leading contributions, Novotech has received numerous prestigious awards, including the Fierce CRO 2024 Excellence Award in Clinical Trial Management and Global Operations, Frost & Sullivan 2024 Global Biotech CRO of the year award, Clinical Trials Arena 2024 Excellence Awards in Business Expansion, Innovation and Marketing, 2024 Employer of Choice, 2024 Great Place to Work in the US, 2024 Brandon Hall Gold Award, CRO Leadership Award 2023, the Asia Pacific Cell & Gene Therapy Clinical Trials Excellence 2023, the Asia-Pacific Contract Research Organization Company of the Year Award since 2006.

Discover more about small-cell lung cancer research by downloading the comprehensive disease report below.

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Merck Axes Two Cancer Candidates After Disappointing Late-Stage Results

Merck announced on Monday that it will discontinue the development of two cancer assets, vibostolimab and favezelimab, following underwhelming Phase III data. The pharma was studying both candidates as combination treatments with the blockbuster therapy Keytruda (pembrolizumab).

Vibostolimab is a monoclonal antibody that works by blocking the TIGIT pathway, in turn restoring the immune system's anticancer activity and boosting the activity of T lymphocytes.

According to the Monday announcement, Merck was running the Phase III KeyVibe-003 and KeyVibe-007 trials, testing a fixed-dose combo of vibostolimab with Keytruda in certain non-small cell lung cancer (NSCLC) populations.However, during a pre-planned analysis, an independent Data Monitoring Committee (DMC) determined that both studies met their respective criteria for futility for the primary endpoint of overall survival, and recommended that both trials be terminated.

Merck also reported an excess of immune-related adverse events in patients treated with vibostolimab plus Keytruda, though this finding is consistent with the known safety profile of dual checkpoint inhibitor therapies, according to the company.

"Considering the totality of the data from the Phase 3 KeyVibe studies, including the efficacy outcomes from KeyVibe-003 and KeyVibe-007, the company has decided to discontinue the Phase 3 KeyVibe-006 trial and other vibostolimab studies," Merck's news release stated.

Monday's announcement ends a disappointing run for vibostolimab. In December 2023, Merck reported that vibostolimab plus Keytruda and docetaxel failed to significantly improve progression-free survival in NSCLC patients who had progressed after immunotherapy and chemotherapy, as compared with docetaxel alone.

In May 2023, the pharma was forced to pull the plug on the Phase III KeyVibe-010 study, which was likewise testing vibostolimab plus Keytruda in resected, high-risk melanoma. The decision was driven by a higher rate of patients dropping out of the combo treatment arm, driven by immune-mediated adverse events.

Because of the patient discontinuations, an independent DMC concluded that it would be "highly unlikely" for the trial to achieve a significant improvement in recurrence-free survival.

A few months later, in August, the pharma revealed that the Phase III KeyVibe-008 study likewise met the futility criteria for its primary efficacy endpoint of overall survival, pushing Merck to discontinue the trial. KeyVibe-008 was testing vibostolimab with Keytruda and chemotherapy in patients with extensive-stage small cell lung cancer.

Aside from vibostolimab, Merck on Monday announced that it would drop the clinical development of the anti-LAG-3 antibody favezelimab following a "thorough evaluation of data from the favezelimab clinical program." Merck will cease enrollment into the KEYFORM-008 study, which was testing favezelimab with Keytruda in relapsed or refractory classical Hodgkin lymphoma patients.

In September favezelimab failed the KEYFORM-007 study, in which it did not significantly improve overall survival in metastatic colorectal patients when combined with Keytruda, as compared with the current standard of care.

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