ABBV-706 as monotherapy and in combination with budigalimab in patients with relapsed/refractory (R/R) small cell lung cancer (SCLC).

Abstract

8008 Background: SCLC is an aggressive cancer with poor prognosis and limited treatment options. Seizure-related 6 homolog (SEZ6) is overexpressed in SCLC. ABBV-706 is a SEZ6-targeting antibody-drug conjugate with topoisomerase 1-inhibitor payload. Here we report updated data from a phase 1 study (NCT05599984) evaluating ABBV-706 in patients (pts) with R/R SCLC as monotherapy or in combination with budigalimab (Budi), an anti-PD-1 immune checkpoint inhibitor (CPI). Methods: The study enrolled pts ≥18 years old with R/R SCLC and Eastern Cooperative Oncology Group performance score ≤1. Pts received either ABBV-706 monotherapy every 3 weeks (Q3W), or in combination with 375 mg Budi Q3W. Results: As of Sept. 27, 2025, 124 pts received ABBV-706 monotherapy. Of these, 41 received the recommended phase 3 dose (1.8 mg/kg), with 17 receiving ABBV-706 as a second-line (2L) therapy. Overall, median age was 64 years, and most pts (65%) received at least 2L of prior treatment. The safety profile was comparable with previously reported data. Median follow-up (mFU) was 16.2 months, and median overall survival (mOS) overall (N=124) and among pts receiving 1.8 mg/kg as 2L (n=17) was 11.3 and 14.3 months, respectively. The 15-month OS estimates for the same cohorts were 40% and 50%, respectively. As of Sept. 27, 2025, 11 pts received ABBV-706 (1.8 mg/kg Q3W) + Budi as 2L treatment. Median age was 68 years. No new safety signals were detected as compared to monotherapy, and there were no reports of pneumonitis. Treatment-related adverse events (TRAEs) occurred in 91% of pts, most commonly gastrointestinal (64%) and hematological (64%). TRAEs grade ≥3 occurred in 46% of pts, with anemia (27%) and neutrophil count decreased (18%) being most common. TRAEs led to treatment discontinuation, interruption, or dose reduction in 0%, 64%, and 36% of pts, respectively. No treatment-related deaths were reported. mFU was 9.1 months. Detailed efficacy endpoints are shown in the Table. Conclusions: ABBV-706 monotherapy shows promising OS benefit in a heavily pretreated pt population with R/R SCLC and is combinable with a CPI. Clinical trial information: NCT05599984 . Efficacy of ABBV-706 in R/R SCLC. MonotherapyTotal(N=124) Monotherapy1.8 mg/kg (n=41) Monotherapy1.8 mg/kg as 2L(n=17) ABBV-706 1.8 mg/kg + Budi(n=11) Best overall response, a,b n (%) Complete response 3 (2) 3 (7) 2 (12) 0 Partial response c 64 (52) 20 (50) 12 (71) 6 (55) Stable disease 46 (37) 16 (39) 2 (12) 3 (27) Progressive disease 6 (5) 1 (2) 1 (6) 1 (9) NE/not assessed 5 (4) 1 (2) 0 1 (9) Objective response rate a (%) 52 56 82 55 Median duration of response, months 5.3 d 5.9 e 6.6 f 6.7 g Median progression-free survival, months 5.4 6.4 6.8 8.1 mOS, months 11.3 12.4 14.3 NE OS estimate at 15 months, % 40 44 50 NE a Confirmed by investigator per RECIST v1.1. b Percentages may exceed 100% due to rounding. c Includes 2 pts with unconfirmed partial response and ongoing treatment. d n=65. e n=23. f n=14. g n=6.