Relatlimab

Vusolimogene oderparepvec (RP1) in combination with nivolumab received breakthrough therapy designation from the FDA for advanced melanoma. A biologics license application under the Accelerated Approval pathway has been filed. The treatment will undergo confirmatory analysis in the phase 3 IGNYTE-3 trial, which is currently enrolling patients with advanced melanoma who progressed on anti–PD-1 and anti–CTLA-4 therapy.

Neoadjuvant ori+tori therapy in resectable stage III and IVM1a acral melanoma (AM) showed 77.8% pathological response, 85.2% 1-year RFS, and 81.5% 2-year RFS, surpassing previous adjuvant therapy alone. Limited data exist on adjuvant or neoadjuvant settings for AM, with most from retrospective studies showing RFS from 14.8 to 26 months. The NADINA study demonstrated neoadjuvant ipilimumab and nivolumab improved EFS over adjuvant nivolumab. AM is less responsive to immunotherapy; anti-PD-1 monotherapy ORR was 18.0% with median PFS of 3–5 months. Combination therapy of anti-PD-1 with oncolytic virus showed 77.8% pathological response, suggesting potential in advanced AM. Oncolytic virus modifies tumor microenvironment, enhancing immune cell activity and sensitivity to immunotherapy. Pathologic response is critical for neoadjuvant therapy efficacy; neoadjuvant ori+tori offered significant advantages over oncolytic virus monotherapy. Safety profiles were favorable, with 13.3% grade 3 AEs. PET/CT showed no correlation with pathological response, necessitating new evaluation technologies. These preliminary data encourage further controlled trials, especially in unresectable metastatic AM.

Neoadjuvant therapy for resectable stage III melanoma is now standard care, validated by ESMO Congress 2024 updates. Pathologic complete response best predicts outcomes. Neoadjuvant ipilimumab plus nivolumab showed superior event-free survival over adjuvant nivolumab in NADINA trial. INMC update revealed best outcomes with anti–PD-1 plus anti–CTLA-4 therapy. Major pathologic response strongly correlates with better survival. Neoadjuvant therapy implementation and biomarker development are crucial for personalized care.

The RELATIVITY-104 study evaluated nivolumab, relatlimab, and platinum doublet chemotherapy as a first-line treatment for metastatic NSCLC. The combination therapy showed higher overall response rates (ORR) compared to nivolumab and chemotherapy alone, especially in patients with PD-L1 expression ≥ 1% and nonsquamous histology. The safety profile was manageable, and further studies are needed to confirm long-term benefits.

Oncology nurses are crucial in guiding patients through clinical trials, including biomarker testing. Elizabeth Burton discussed a longitudinal biomarker analysis from a phase 2 trial of neoadjuvant nivolumab and relatlimab in resectable melanoma, highlighting the importance of gene expression profiling and the potential of B7-H3 protein in predicting response.

Global LAG-3 Inhibitors Market expected to exceed USD 3 billion by 2029; Opdualag, first LAG-3 therapy, approved for melanoma. LAG-3 inhibitors show potential in combination therapies for various cancers and diseases. Key players include Bristol Myers Squibb, Roche, and Regeneron. Market valued at USD 625 million in 2023, projected to grow significantly.

Global LAG-3 inhibitors market to exceed USD 3 billion by 2029, driven by the approval of Opdualag, the first LAG-3 therapy, and ongoing clinical trials evaluating LAG-3 inhibitors in combination therapies. Key players include Bristol Myers Squibb, Symphogen A/S, and Hoffmann-La Roche.

Studies explore colorectal cancer recurrence, immunotherapy response, and biomarker development, focusing on microsatellite instability, mismatch repair deficiency, and tumor mutational burden. Key findings include the efficacy of PD-1 blockade in mismatch repair-deficient cancers, the role of gut microbiota in immunotherapy, and the predictive value of tumor mutational burden for immune checkpoint inhibitor response.

AstraZeneca's Imfinzi in bladder cancer reduced death risk by 25%; Merck and Eisai's combo in liver cancer cut progression or death risk by a third; Bristol's lung cancer approach faced criticism for 'cherry-picking' subgroups.

NICHE-3 study, approved by NedMec, enrolled adults with dMMR resectable colon adenocarcinoma. Patients received nivolumab and relatlimab, followed by surgery. Primary endpoint was pathologic response (≤50% RVT), with secondary endpoints including safety and survival. Study used a Simon’s two-stage design, aiming for a response rate of 85%. Pathologic response was assessed by central histopathologic review. Safety and efficacy populations were defined, with binary endpoints reported as proportions. MMR status was assessed via immunohistochemistry.