Respiratory Research Analysis
June’s respiratory research delivered practice-shifting advances across oncology, tuberculosis, vaccines, and AI-driven discovery. Two large phase 3 trials reshaped thoracic oncology: a DLL3-directed T‑cell engager (tarlatamab) improved survival in relapsed SCLC, and a third‑generation EGFR TKI (limertinib) more than doubled PFS versus gefitinib. A four‑month clofazimine‑containing regimen supported safe treatment shortening for drug‑susceptible pulmonary TB, while an affordable, locally manufac
Summary
June’s respiratory research delivered practice-shifting advances across oncology, tuberculosis, vaccines, and AI-driven discovery. Two large phase 3 trials reshaped thoracic oncology: a DLL3-directed T‑cell engager (tarlatamab) improved survival in relapsed SCLC, and a third‑generation EGFR TKI (limertinib) more than doubled PFS versus gefitinib. A four‑month clofazimine‑containing regimen supported safe treatment shortening for drug‑susceptible pulmonary TB, while an affordable, locally manufacturable NDV‑based COVID‑19 booster showed strong immunogenicity for LMIC deployment. Mechanistically, a deep generative single‑cell model (UNAGI) prioritized repurposable anti‑fibrotic candidates validated in human lung tissue, underscoring AI’s accelerating role in respiratory therapeutics.
Selected Articles
1. Phase 2/3 study evaluating safety, immunogenicity, and noninferiority of single booster dose of AVX/COVID-12 vaccine.
A double-blind, active-controlled phase 2/3 noninferiority RCT (n=4,056) of an NDV-LaSota HexaPro-S booster (AVX/COVID-12) showed favorable safety and robust neutralizing antibody responses to ancestral SARS-CoV-2 and Omicron BA.2/BA.5, with CD8 IFN-γ responses, supporting locally manufacturable, low-cost deployment.
Impact: Demonstrates an affordable, locally manufacturable vaccine booster with variant-specific immunogenicity, directly addressing equity and cold-chain barriers in LMICs.
Clinical Implications: NDV-based boosters can be considered by public health programs where mRNA logistics are impractical; effectiveness against infection/hospitalization and durability against new variants should be further evaluated.
Key Findings
- Double-blind, active-controlled phase 2/3 noninferiority design with 4,056 participants.
- Neutralizing antibodies to ancestral and Omicron BA.2/BA.5 plus CD8+ IFN-γ responses.
- Platform enables cost-effective local manufacturing suitable for LMIC deployment.
2. Efficacy and safety of limertinib versus gefitinib as first-line treatment for locally advanced or metastatic non-small-cell lung cancer with EGFR-sensitising mutation: a randomised, double-blind, double-dummy, phase 3 trial.
A multicenter, double-blind phase 3 RCT (n=337) showed limertinib more than doubled ICR-assessed PFS versus gefitinib (20.7 vs 9.7 months; HR 0.44) with comparable grade ≥3 adverse events, supporting limertinib as a first-line EGFR TKI option.
Impact: Phase 3 superiority on disease control in EGFR-mutant NSCLC likely influences first-line standards, especially where gefitinib remains in use.
Clinical Implications: Consider limertinib among first-line EGFR TKI choices; comparative data versus osimertinib and CNS outcomes will refine positioning.
Key Findings
- Median ICR-assessed PFS 20.7 vs 9.7 months (HR 0.44; p<0.0001).
- Grade ≥3 treatment-related AEs were 25% in each arm.
- Randomised, double-blind, double-dummy design across 56 centers with stratification.
3. A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases.
UNAGI models time-series single-cell transcriptomic dynamics to prioritize drug candidates; in idiopathic pulmonary fibrosis, it predicted repurposable agents and validated nifedipine’s anti-fibrotic effects in human precision-cut lung slices with proteomic support.
Impact: Bridges single-cell disease trajectories with actionable drug prioritization and ex vivo validation, accelerating respiratory therapeutic discovery.
Clinical Implications: Offers a preclinical prioritization platform for repurposing and early-phase trials in pulmonary fibrosis; informs candidate and biomarker selection.
Key Findings
- Captured time-resolved single-cell disease trajectories and improved drug perturbation modeling.
- Predicted candidates for pulmonary fibrosis; nifedipine showed anti-fibrotic effects ex vivo.
- Proteomic validation supported inferred dynamics; framework generalized to other diseases.
4. Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy.
In a multinational phase 3 RCT (n=509), the DLL3-directed T-cell engager tarlatamab improved median OS versus physician-choice chemotherapy (13.6 vs 8.3 months; HR 0.60) with fewer grade ≥3 adverse events and better patient-reported respiratory symptoms.
Impact: First definitive phase 3 evidence that a DLL3-engager outperforms chemotherapy in previously treated SCLC, addressing a long-standing unmet need.
Clinical Implications: Supports tarlatamab as a preferred second-line option after platinum therapy, with monitoring for CRS and neurologic events.
Key Findings
- Median OS 13.6 vs 8.3 months; HR 0.60, P<0.001.
- Lower grade ≥3 AEs (54% vs 80%) and fewer discontinuations (5% vs 12%).
- Improved PFS and patient-reported dyspnea/cough.
5. Four-month clofazimine regimen for susceptible pulmonary TB: a randomized clinical trial.
CORTAIL, a multicenter randomized non-inferiority trial (n=322), found a 16-week clofazimine-based regimen comparable to the standard 24-week therapy in relapse, sputum conversion, and bacteriologic cure, with acceptable safety.
Impact: Provides high-level RCT support for safely shortening first-line treatment of drug-susceptible pulmonary TB from six to four months.
Clinical Implications: If validated broadly, a 4-month clofazimine-containing regimen could be adopted as a new standard, especially where adherence to longer courses is challenging.
Key Findings
- Non-inferiority for relapse at 3 months post-treatment within predefined margin.
- No significant difference in 1-year relapse, sputum conversion, or bacteriologic cure.
- Acceptable safety profile across 11 centers.