Abstract
OA06.04 Safety and Efficacy of ABBV-706, a Seizure-related Homolog Protein 6-targeting Antibody-drug Conjugate, in R/R SCLC
Journal of thoracic oncology, Vol.20(10 Suppl 1), p.S23
10/2025
DOI: 10.1016/j.jtho.2025.09.049
Abstract
Introduction
Seizure-related homolog protein 6 (SEZ6) is highly expressed in small cell lung cancer (SCLC). ABBV-706, an antibody-drug conjugate (ADC) comprising a SEZ6-targeting antibody with a topoisomerase 1 inhibitor (Top1i) payload, was evaluated in a phase 1 study (NCT05599984). Preliminary results from dose escalation (1.3 to 3.5 mg/kg Q3W) showed encouraging antitumor activity and manageable safety of ABBV-706 monotherapy in patients with advanced solid tumors (JCO 2024;42:suppl16;abstr 3001). We present updated safety and efficacy results for patients with SCLC in the dose optimization cohorts.
Methods
Patients (≥18 years) with relapsed/refractory (R/R) SCLC were randomized to receive ABBV-706 at 1.8 or 2.5 mg/kg Q3W until disease progression/unacceptable toxicity. SEZ6 expression was assessed retrospectively. Patients with prior treated or untreated stable brain metastases were eligible. Prior exposure to SEZ6-targeted ADCs or ADCs with Top1i payload was not permitted. Primary objectives were to assess efficacy, safety, pharmacokinetics, and determine the recommended phase 2 dose (RP2D) in SCLC.
Results
In total, 80 patients with SCLC were enrolled: 1.8 mg/kg, n=41; 2.5 mg/kg, n=39. Median number of prior therapies was 2 (range: 1-6); median treatment duration was 5.8 months (range: 0.7-11.3). SEZ6 expression and patient characteristics were balanced between the dose cohorts. ABBV-706 showed similar ORR at both doses, with longer DOR and PFS at 1.8 mg/kg (see Table). ORR was higher in patients who were Top1i naive and/or receiving ABBV-706 in second line (62.1% and 81.3% at 1.8 mg/kg). The 1.8-mg/kg dose had improved safety vs 2.5 mg/kg. Relative dose intensity was 99% and 85% at 1.8 mg/kg and 2.5 mg/kg. Any-grade (G) treatment-related adverse events (TRAEs) in the 1.8-mg/kg and 2.5-mg/kg cohorts occurred in 85% and 95% of patients; most common were anemia (51% vs 74%) and fatigue (34% vs 39%). G≥3 TRAEs in the 1.8-mg/kg and 2.5-mg/kg cohorts occurred in 49% and 77% of patients; anemia (39% vs 62%) and neutrophil count decreased (17% vs 31%) were most common. Serious TRAEs occurred in 17% (1.8 mg/kg) and 10% (2.5 mg/kg) of patients. Overall, TRAEs leading to dose discontinuation, interruption, reduction, and death occurred in 9%, 44%, 28%, and 4% of patients. Adjudicated interstitial lung disease rate was 9%.
Conclusions
ABBV-706 has manageable safety and promising efficacy in patients with R/R SCLC. Based on the totality of the benefit-risk profile, monotherapy RP2D was determined to be 1.8 mg/kg Q3W in SCLC.
Details
- Title: Subtitle
- OA06.04 Safety and Efficacy of ABBV-706, a Seizure-related Homolog Protein 6-targeting Antibody-drug Conjugate, in R/R SCLC
- Creators
- L.A. ByersB. Chul ChoA. CooperA.C. ChiangJ.-Y. HanD. MorgenszternM. FurqanA. DowlatiJ. BarJ.-H. KimH. YokouchiL. Paz-AresD. MeimanW. MunasingheO. OgunyankinR.R. RobinsonC. FerliniF.J. KohlhappP. HingoraniS. Chandana
- Resource Type
- Abstract
- Publication Details
- Journal of thoracic oncology, Vol.20(10 Suppl 1), p.S23
- DOI
- 10.1016/j.jtho.2025.09.049
- ISSN
- 1556-0864
- Language
- English
- Date published
- 10/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9985019030602771
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