Clinical Trial News

U.S. Senators introduced the FDA Modernization Act 3.0 to mandate FDA update regulations within six months, aligning with FDAMA 2.0, which removed mandatory animal testing for investigational new drugs in 2022.

Trastuzumab deruxtecan (T-DXd) improved physical/role functioning and pain in HR+, HER2-low/-ultralow metastatic breast cancer patients compared to treatment of physician’s choice (TPC), with significant reductions in pain deterioration (22.0 months vs 6.3 months) and other symptoms, while maintaining global health/QOL over 31 weeks.

The APOLLO trial at ESMO 2024 showed Chia Tai Tianqing's Focus V and Akeso's penpulimab significantly improved PFS and OS in advanced hepatocellular carcinoma (aHCC) compared to sorafenib, with a manageable safety profile. This contrasts with the failure of Merck & Co's Keytruda in the LEAP-002 trial. Competitive IO-TKIs like Elevar Therapeutics' camrelizumab and rivoceranib also showed benefits but with more TRAEs. Roche's Tecentriq with bevacizumab remains the first-line standard-of-care in aHCC, posing a challenge to new IO-TKI combinations.

ESMO 2024 session on rare genitourinary cancers featured updates on penile cancer by Prof. Andrea Necchi, highlighting geographic variation in incidence, surgical indications, and treatment trends. Key updates included neoadjuvant chemotherapy recommendations and ongoing challenges in patient selection for perioperative therapy. Clinical trials like InPACT and HERCULES evaluated neoadjuvant therapies, while systemic therapy options for metastatic cases were also discussed. HPV status and tumor mutational burden (TMB) were noted to influence treatment outcomes. Ongoing research emphasizes the need for tailored approaches and clinical trial participation.

WHO approved Bavarian Nordic's MVA-BN mpox vaccine for adults, with conditional use for babies, children, teens, and pregnant women in outbreak settings. Critics argue the vaccine's safety and efficacy in pediatric populations are unproven, questioning WHO's approval. The vaccine, sold as Jynneos in the US, is also criticized for diverting resources from broader public health issues in Africa.

Dr. Himisha Beltran discussed DLL3 as a therapeutic target for neuroendocrine prostate cancer at the 2024 ESMO Congress. DLL3 expression increases in castrate-resistant prostate cancer and is crucial for maintaining a neuroendocrine phenotype. Despite early promising results with DLL3-targeted therapies like Rova-T, efficacy was limited and toxicity high. Ongoing DLL3-targeted therapies include T cell engagers, ADCs, radionuclides, and CAR-T. Tarlatamab, a DLL3-targeted bi-specific T cell engager, showed limited efficacy in neuroendocrine prostate cancer. MK-6070, another DLL3-targeted T cell engager, demonstrated strong anti-tumor activity in neuroendocrine prostate cancer models. Future PET imaging with ⁸⁹Zr-SC16 may aid in patient selection and resistance pattern understanding.

Analysis of 2,240 CRC patients showed ctDNA status post-surgery significantly predicts recurrence and survival. MRD-positive patients had higher recurrence rates and worse DFS and OS than MRD-negative. ctDNA clearance on ACT correlated with better outcomes. MRD status outperformed traditional biomarkers in predicting CRC prognosis.

Nivolumab (Opdivo) with or without ipilimumab (Yervoy) significantly improved 10-year overall and melanoma-specific survival in advanced melanoma patients compared to ipilimumab alone, according to the CheckMate 067 trial. The 10-year overall survival rates were 43%, 37%, and 19% for nivolumab/ipilimumab, nivolumab monotherapy, and ipilimumab monotherapy, respectively.

25 patients with SCLC were enrolled and treated; 60% showed partial response, 76% disease control rate. Median PFS was 6.0 months, mOS 13.4 months. 92% experienced treatment-related adverse events, most common being leukopenia, anemia, and elevated GGT. ctDNA analysis revealed frequent TP53, MUC16, RB1, DNMT3A, and ZFHX4 mutations. KMT2D mutations negatively impacted survival and treatment response. High on-treatment bTMB correlated with improved PFS and OS, suggesting it as a predictive biomarker.

Combining radium-223 with enzalutamide significantly extended radiological progression-free survival and overall survival in advanced prostate cancer patients with bone metastases, according to the PEACE-3 trial. A bone-protecting agent is mandatory when using this combination. The median radiological progression-free survival was 19.4 months in the combination arm vs 16.4 months in the enzalutamide-only arm. Median overall survival was 42.3 months vs 35.0 months, respectively.