Tarlatamab and Next-Generation Targeted Agents Headline ESMO 2026 Lung Cancer Data

Lung cancer produced some of the most decisive survival data at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid. A bispecific T-cell engager moved into first-line maintenance, a head-to-head trial reordered KRAS G12C inhibitors, and TROP2-directed antibody-drug conjugates (ADCs) kept advancing. Each shift brings new monitoring and counseling work for pharmacists.

DeLLphi-305: Tarlatamab Moves Into Maintenance

In the phase 3 DeLLphi-305 trial (NCT06211036), adding tarlatamab (Imdelltra; Amgen) to durvalumab (Imfinzi; AstraZeneca) maintenance after first-line durvalumab plus platinum-etoposide nearly doubled median OS in extensive-stage small cell lung cancer (21.1 vs 12.7 months; HR, 0.42; 95% CI, 0.32-0.54). Median progression-free survival (PFS) was 7.4 vs 1.9 months (HR, 0.34), and the benefit held in patients with brain or liver metastases.^1,2

Cytokine release syndrome (CRS) occurred in 49.6% of patients, with 1 grade 3 event, and immune effector cell–associated neurotoxicity syndrome occurred in 1.1%.² Moving tarlatamab earlier means more patients on longer treatment, which makes step-up dosing protocols, CRS education, and outpatient monitoring plans core pharmacy work.

Krascendo 1: A New Leader Among KRAS G12C Inhibitors

The phase 3 Krascendo 1 trial (NCT06497556) compared divarasib (Genentech) with sotorasib (Lumakras; Amgen) or adagrasib (Krazati; Bristol Myers Squibb) in previously treated KRAS G12C–mutated non–small cell lung cancer (NSCLC). Divarasib improved median PFS (9.8 vs 5.7 months; HR, 0.58; 95% CI, 0.44-0.76) and OS (17.7 vs 12.0 months; HR, 0.56; 95% CI, 0.41-0.78), with a confirmed response rate of 58.4% vs 32.3%. Grade 3 or 4 treatment-related adverse events (AEs) were less frequent (24.6% vs 34.5%).³ Diarrhea, nausea, and vomiting were more common but mostly grade 1, so proactive antiemetic and antidiarrheal counseling will matter if divarasib reaches the market.⁴

SAFFRON: Treating MET-Driven Resistance

In the phase 3 SAFFRON trial (NCT05261399), osimertinib (Tagrisso; AstraZeneca) plus savolitinib (Orpathys; AstraZeneca, HUTCHMED) outperformed platinum-pemetrexed in EGFR-mutated NSCLC with MET overexpression and/or amplification after progression on osimertinib. Median PFS was about 7.6 vs 5.4 months (HR, 0.55; 95% CI, 0.42 to 0.72), and median OS was 17.8 vs 12.9 months (HR, 0.68; 95% CI, 0.50 to 0.91).⁵ Peripheral edema affected approximately 49% of patients receiving the combination, and fatal AEs occurred in 7% compared with none receiving chemotherapy.⁵ The results make MET testing at osimertinib progression more pressing.

TROP2 ADCs Keep Gaining Ground

Final OS from the phase 3 OptiTROP-Lung04 trial (NCT05870319) favored sacituzumab tirumotecan (Kelun-Biotech, Merck) over platinum-based chemotherapy in EGFR-mutated NSCLC after EGFR tyrosine kinase inhibitor therapy (25.9 vs 17.4 months; HR, 0.69; 95% CI, 0.54-0.89).⁶ In the first-line setting, OptiTROP-Lung06 (NCT06711900) showed that sacituzumab tirumotecan plus pembrolizumab (Keytruda; Merck) extended median PFS vs pembrolizumab plus platinum chemotherapy in PD-L1–negative nonsquamous NSCLC (15.0 vs 5.7 months; HR, 0.49; 95% CI, 0.36-0.65), with fewer grade 3 or higher AEs. OS data are immature.⁷

The Takeaway

These regimens are more effective, and they also ask more of the people who give them. Bispecific monitoring, combination oral targeted therapies, and ADC toxicity management are moving into earlier lines, and pharmacists will carry much of that operational load.

REFERNECES

1. Sands J, et al. Tarlatamab–durvalumab maintenance for extensive-stage small-cell lung cancer. N Engl J Med. Published online October 2026. doi:10.1056/NEJMoa2609482

2. Sands J. Tarlatamab plus durvalumab (durva) vs durva as 1L maintenance (1LM) therapy following durva, platinum, and etoposide (1L durva + EP) in extensive-stage small cell lung cancer (ES-SCLC): primary analysis of the phase 3 DeLLphi-305 trial. Presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract LBA3.

3. Skoulidis F, Ahn MJ, Gadgeel S, et al. Divarasib as compared with sotorasib or adagrasib in KRAS G12C–mutated NSCLC. N Engl J Med. Published online October 25, 2026. doi:10.1056/NEJMoa2605703

4. Skoulidis F. Krascendo 1: efficacy and safety of divarasib (diva) vs sotorasib (soto) or adagrasib (ada) in previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC. Presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract LBA5.

5. Lu S. Osimertinib (osi) + savolitinib (savo) vs platinum–pemetrexed (plat–pem) in EGFRm MET-overexpressed (OE) and/or -amplified (AMP) advanced NSCLC post-osi: SAFFRON phase (Ph) 3 primary results. Presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract LBA6.

6. Fang W. Final OS analysis of sacituzumab tirumotecan (sac-TMT) versus platinum-based chemotherapy in EGFR-mutated non-small cell lung cancer (NSCLC) after progression on EGFR-TKI: phase III OptiTROP-Lung04 study. Presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract LBA67.

7. Zhou C. Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (P) versus chemotherapy (chemo) plus pembrolizumab (P) as first-line (1L) treatment for PD-L1-negative advanced non-squamous (nsq) NSCLC: randomized phase 3 OptiTROP-Lung06 study. Presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract LBA66.