Relatlimab

IL-6 blockade with tocilizumab may reduce immunotherapy-related toxicities in melanoma patients treated with ipilimumab and nivolumab, showing promising efficacy and reduced toxicity rates in a phase 2 study.

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.

Bristol Myers Squibb stock rose 10% after AbbVie's mid-stage clinical trials for Emraclidine failed, boosting BMY's recently FDA-approved schizophrenia drug Cobenfy. BMY's revenue rose 1% to $47 billion, with new drugs like Camzyos, Sotyktu, and Opdualag expected to generate over $1 billion each by 2026. Despite a slight decline in operating margin to 15.3%, BMY's recent acquisitions and Cobenfy's potential peak sales of over $6 billion suggest growth potential.

Bristol Myers Squibb reported Q3 revenues of $11.89B, up 8% YoY, driven by Growth Portfolio and Eliquis. Growth Portfolio revenues rose 18% to $5.81B, led by Reblozyl, Breyanzi, Camzyos, and Opdualag. Opdivo sales grew 4% to $2.36B, and Abecma sales surged 33% to $124M. Eliquis sales reached $3B, offsetting Sprycel's decline. Adjusted EPS was $1.80, beating consensus of $1.49. The company anticipates $1.5B in cost savings for 2025 and forecasts 2024 adjusted EPS of $0.75-$0.95. BMY stock rose 5.18% to $55.39.

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.

Regeneron, despite being a latecomer in cancer therapies, aims to leverage its packed pipeline to become a leader in the next wave of oncology treatments. Dr. Israel Lowy, senior vice president of translational and clinical sciences in oncology, highlights the company's focus on combinations like Libtayo and fianlimab, which could rival existing treatments like Opdualag and Keytruda. Regeneron's journey includes pioneering bispecific antibodies and facing early challenges, but with ongoing clinical trials and collaborations, the company seeks to establish itself as a major player in cancer therapy.