Introduction to ASCO 2025 Lung Cancer Immunotherapy Updates
At the MOASC/ANCO Immuno-Oncology Symposium held on September 6, 2025, in Marina del Rey, Dr. Navid Hafez, MD, MPH, delivered a compelling overview of ASCO 2025’s most impactful lung cancer immunotherapy data. Drawing from the symposium’s focus on advancing cancer care in California, Dr. Hafez highlighted transformative results in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). These updates, rooted in Phase III trials, emphasize improved pathologic complete response (pCR) rates and overall survival (OS) benefits. Even the role of infusion timing was emphasized. For Northern California’s oncology community, these insights offer immediate strategies to optimize patient outcomes amid evolving treatment paradigms.
Deep Dive into Key Lung Cancer Immunotherapy Trials
CheckMate-816: Neoadjuvant Nivolumab’s Long-Term Impact in Resectable NSCLC
The CheckMate-816 trial stood out as one of ASCO 2025’s biggest updates. It confirmed an OS benefit for neoadjuvant nivolumab combined with platinum-based chemotherapy (carboplatin or cisplatin) in resectable NSCLC. Updated 5-year data revealed a pathologic complete response (pCR) rate of approximately 25% with the addition of nivolumab. This rate was higher than those seen in other perioperative studies. Dr. Hafez cautioned against direct cross-trial comparisons but noted, “PCR definitely improves outcomes.” Exploratory analyses showed markedly better event-free survival (EFS) and OS in patients achieving pCR.
This flexibility in chemotherapy choice is clinically vital. Carboplatin, often better tolerated, still delivered strong results. This makes the regimen accessible for patients with reservations about cisplatin. As Dr. Hafez explained, “Knowing that you still have great outcomes and an overall survival benefit with that drug… helps us.” These stats underscore nivolumab’s role in shifting early-stage NSCLC toward more curative intents. PCR serves as a robust predictor of long-term success.
DeLLphi-304: Tarlatamab Establishes New Standard in Relapsed SCLC
For previously treated SCLC, the Phase III DeLLphi-304 trial solidified tarlatamab—a DLL3/CD3 bispecific T-cell engager—as a game-changer. Compared to physician’s choice chemotherapy (including lurbinectedin or topotecan), tarlatamab demonstrated a clear OS benefit across the intent-to-treat population. Subgroup analyses, though not powered for formal comparisons, showed consistent advantages over individual chemo options. Dr. Hafez stated, “Whether patients had lurbinectedin or topotecan as their second-line drug, we still saw this improvement in overall survival.”
Already approved based on Phase II data, tarlatamab is now “entrenched as the standard of care for second-line in small cell lung cancer after progression on first-line chemo-immunotherapy.” This trial addresses a high-need area, where rapid progression often limits options. It provides oncologists with a targeted therapy that outperforms traditional cytotoxics.
Infusion Timing: Circadian Rhythms and Immunotherapy Efficacy in Stage 4 NSCLC
Dr. Hafez’s “favorite study” from ASCO 2025 was the Phase III analysis by Zhang et al. It revealed that administering immunotherapy before 3 p.m. yields profound PFS and OS improvements in stage 4 NSCLC. Survival curves “split so dramatically early and continue to grow with time.” This is linked to immunologic shifts. Early-day infusions boost CD8+ effector T-cell counts and improve the effector-to-suppressor cell ratio. In contrast, late-day dosing shows declines.
Correlative data further illuminated the mechanism—potentially tied to morning cortisol levels and circadian rhythms. Active versus exhausted T-cell ratios favor early infusions. Dr. Hafez mused on broader implications, questioning whether early-morning dosing in Phase I trials inflated early promises that later faded. This simple yet powerful stat could prompt immediate practice changes: prioritizing pre-3 p.m. slots to harness natural immune dynamics.
Clinical Implications and Unmet Needs
These ASCO 2025 lung cancer immunotherapy updates collectively address key challenges. In resectable NSCLC, CheckMate-816’s 25% pCR and OS gains via early nivolumab integration elevate neoadjuvant standards. For relapsed SCLC, DeLLphi-304’s OS edge with tarlatamab fills a second-line void. Meanwhile, the timing study’s CD8+ enhancements highlight modifiable factors in advanced NSCLC. As Dr. Hafez emphasized, these findings “opened up a world of questions,” urging further research into immunology and trial design.
Presented at the Immuno-Oncology Symposium, these insights empower California oncologists to refine protocols, from chemo flexibility to scheduling. The ANCO network amplifies such knowledge through education, advocacy, and local resources like clinical trial access.
Call to Action
Join MOASC or ANCO today for ongoing symposium recordings, job boards, and reimbursement guidance. Dive into Dr. Hafez’s full ASCO 2025 presentation from the event to unpack these lung cancer immunotherapy stats. Share your thoughts on X with #ImmunoOncology2025 and connect with peers advancing cancer care!
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