Advancing NSCLC Care: RMAT Status, Treatment Timing, and ASCO Updates

Recent clinical developments in non-small cell lung cancer (NSCLC) highlight the critical roles of treatment timing, comprehensive molecular profiling, and innovative delivery systems in improving patient outcomes.

FDA Regenerative Medicine Advanced Therapy Status Granted to KB707 in Advanced NSCLC

The FDA has granted regenerative medicine advanced therapy (RMAT) designation to KB707 for the treatment of advanced or metastatic NSCLC.¹ KB707 is an inhaled, re-dosable immunotherapy designed to drive the localized expression of interleukin-2 (IL-2) and interleukin-12 (IL-12) directly within the tumor microenvironment.

The RMAT designation is intended to expedite the development of therapies for serious or life-threatening conditions. This status provides the benefits of fast track and breakthrough therapy designations, including intensive FDA guidance, organizational commitment from senior agency managers, and the potential for rolling review of the marketing application. Early clinical evidence from the ongoing KYANITE-1 study (NCT06228326) supported this designation, showing antitumor activity and durable responses in heavily pretreated patients. Enrollment in this study continues to further evaluate the efficacy and safety of this novel delivery method.

Time of Immunochemotherapy Administration May Significantly Impact Survival in Patients With NSCLC

Evidence from the randomized phase 3 LungTIME-C01 trial (NCT05549037) suggests that the time of day (ToD) for immunochemotherapy administration may influence efficacy.² The study included 210 patients with treatment-naive stage IIIC to IV NSCLC lacking driver mutations who were randomized to receive the first 4 cycles of an anti–PD-1 agent either before or after 3 pm.

After a median follow-up of 28.7 months, patients in the early ToD group demonstrated a median progression-free survival (PFS) of 11.3 months (95% CI, 9.2-13.4) compared with 5.7 months (95% CI, 5.2-6.2) in the late ToD group. Overall survival (OS) also favored the early group, reaching 28.0 months (95% CI, NE-NE) vs 16.8 months (95% CI, 13.7-19.9) for those treated after 3 pm.

Biological analysis indicated that early administration was associated with an increase in morning circulating CD8-positive T-cells and a higher ratio of activated vs exhausted CD8-positive T cells. Notably, treatment-related adverse events (AEs) were consistent with established safety profiles, with no significant differences in immune-related adverse events between the 2 groups.

ASCO Updates Living Guidelines for Patients With Stage IV NSCLC With Driver Alterations

The American Society of Clinical Oncology (ASCO) recently published a 2026 update to its living guideline for stage IV NSCLC with driver alterations, incorporating new evidence and therapeutic approvals.³ A central recommendation is the use of broad next-generation sequencing (NGS) panels combined with immunohistochemistry (IHC) for PD-L1, HER2, and MET. Guideline chairs emphasize that sequential single-gene testing is inefficient for tissue utilization and should be avoided outside of resource-limited settings.

The updated guidelines highlight several new therapeutic options based on clinical trial data:

• ROS1 rearrangements: Taletrectinib (Ibtrozi) is now included as an option for both first- and second-line settings.
• HER2 exon 20 mutations: Zongertinib (Hernexeos) and sevabertinib (Hyrnuo) are recommended for patients previously treated with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu).
• EGFR exon 20 insertion: Sunvozertinib (Zegfrovy) is added as a subsequent therapy option following progression on platinum-based chemotherapy with or without amivantamab-vmjw (Rybrevant).
• MET amplification: For patients progressing on EGFR-targeted therapy, the combination of osimertinib (Tagrisso) with either tepotinib (Tepmetko) or savolitinib is recommended.

References

1. Krystal Biotech announces RMAT designation granted by FDA to KB707 for the treatment of advanced or metastatic non-small cell lung cancer. Krystal Biotech, Inc. News release. February 9, 2026. Accessed February 11, 2026. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-rmat-designation-granted-fda-kb707
2. Huang Z, Zeng L, Ruan Z, et al. Time-of-day immunochemotherapy in non-small cell lung cancer: a randomized phase 3 trial. Nat Med. Published online February 2, 2026. doi:10.1038/s41591-025-04181-w
3. Tanzola M. Biomarker testing, incorporation of new drug approvals among new guidance in updated living guideline on stage IV NSCLC with driver alterations. ASCO Post. February 3, 2026. Accessed February 11, 2026. https://dailynews.ascopubs.org/do/biomarker-testing-incorporation-new-drug-approvals-among-new-guidance-updated-living