Ivonescimab Combo Yields Encouraging Activity in Previously Treated SCLC

Combining ivonescimab (Akeso) with liposomal irinotecan (Onivyde) produced encouraging activity among patients with small cell lung cancer (SCLC) who previously received chemoimmunotherapy, according to findings from a phase 2 study (NCT06478043) presented at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO).¹

Among 60 evaluable patients, the treatment combination yielded a 6-month progression-free survival (PFS) rate of 69.1% (95% CI, 55.5%-79.3%). Additionally, the median PFS was 8.1 months (95% CI, 6.5-10.0), and the 12-month rate was 25.7% (95% CI, 13.4%-39.8%).

Across the overall population, the (ORR) was 61.7% (95% CI, 48.2%-73.9%), the disease control rate (DCR) was 96.7% (95% CI, 88.5%-99.6%). Among patients with platinum-sensitive disease and a chemotherapy-free interval (CFI) of at least 90 days (n = 38), these respective values were 63.2% (95% CI, 46.0%-78.2%), 94.7% (95% CI, 82.3%-99.4%), and 8.6 months (95% CI, 5.9-10.2). Additionally, the values were 59.1% (95% CI, 36.4%-79.3%), 100.0% (95% CI, 84.6%-100.0%), and 6.7 months (95% CI, 2.8-13.8) among those with platinum-resistant disease and a CFI below 90 days (n = 22).

Regarding the best tumor change from baseline in target lesions, the median depth of response was –47.9% (range, –84.6% to 20.6%). With a median follow-up of 11.4 months (95% CI, 9.7-13.1), the median duration of response (DOR) was 7.3 months (95% CI, 5.9-10.2), the 12-month DOR rate was 25.1% (95% CI, 9.4%-44.5%); treatment was ongoing in 25.0% (n = 15/60) of patients at the time of analysis.

Data showed a median overall survival (OS) that was not reached (NR; 95% CI, 12.6-not evaluable). Furthermore, the OS rate was 93.3% at 6 months and 74.1% at 12 months.

“Ivonescimab combined with liposomal irinotecan demonstrated promising efficacy for patients with chemoimmunotherapy-treated SCLC,” presenting study author Yun Fan, MD, from the Department of Thoracic Medical Oncology at Zhejiang Cancer Hospital in Hangzhou, China, stated during the presentation. “The safety profile was manageable and consistent with the known profiles of the individual agents.”

In the multicenter, single-arm study, patients were assigned to receive ivonescimab at 20 mg/kg every 3 weeks plus liposomal irinotecan at 56.5 mg/m² every 2 weeks in each 6-week cycle. Treatment continued until progressive disease or unacceptable toxicity.

The trial’s primary end point was the 6-month PFS rate per RECIST v1.1 criteria. Secondary end points included ORR, PFS, DOR, OS, and safety.

Patients 18 to 75 years old with histologically or cytologically confirmed extensive-stage SCLC, an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months were eligible for enrollment on the trial.² Other eligibility criteria included having progression on frontline platinum-based chemotherapy with checkpoint inhibitors, at least 1 measurable lesion per RECIST v1.1 guidelines, and adequate organ function.

The median patient age was 62 years (range, 38-75), and most were male (93.3%). Most of the study population had current or former smoking status (91.7%), an ECOG performance status of 1 (88.3%), extensive-stage disease (95.0%), no liver metastases (65.0%), no brain metastases (73.3%), and a CFI of at least 90 days (63.3%).

Treatment-related adverse effects (TRAEs) of any grade and grade 3 or higher occurred in 96.7% and 36.7% of patients, respectively. Additionally, TRAEs leading liposomal irinotecan dose reduction and discontinuation occurred in 26.7% and 6.7% of patients, respectively; 11.7% discontinued ivonescimab due to toxicity. No patients had TRAEs leading to death.

The most common TRAEs of any grade included anemia (66.7%), diarrhea (48.3%), fatigue (46.7%), and white blood cell count decreases (45.0%). Grade 3 toxicities included fatigue (8.3%), decreased neutrophil counts (8.3%), and decreased white blood cell counts (6.7%). Regarding grade 4 TRAEs, there were singular instances of decreased white blood cell counts and decreased neutrophil counts.

Immune-related TRAEs occurred in 36.7% of patients and included immune-related pneumonitis (10%), rash (10%), and alanine aminotransferase increases (6.7%). Of note, 5 patients with immune-related pneumonitis had prior radiotherapy, which included 4 who previously experienced radiation pneumonitis. VEGF-associated TRAEs were reported in 40% of patients, the most common of which included proteinuria (23.3%), hemorrhage (20%), and hypertension (10%).

References

1. Fan Y, Chen K, Li H, et al. Efficacy and safety of ivonescimab combined with liposomal irinotecan in patients with small-cell lung cancer (SCLC) progressing after first-line chemoimmunotherapy: a multicenter, phase 2 study. J Clin Oncol. 2026;44(suppl 16):8007. doi:10.1200/JCO.2026.44.16_suppl.8007
2. A study to investigate the efficacy and safety of ivonescimab combined with irinotecan liposome as second-line regimen for ES-SCLC. ClinicalTrials.gov. Updated July 8, 2024. Accessed June 2, 2026. https://tinyurl.com/mm5nckmr