Dr Johnson on ABBV-011 in Small Cell Lung Cancer

Melissa L. Johnson, MD, director, Lung Cancer Research, Sarah Cannon Research Institute; chair, Oncology Department, member, Medical Executive Committee, TriStar Centennial Medical Center, discusses the development of the seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate (ADC) ABBV-011 and outcomes with this agent in patients with small cell lung cancer (SCLC).

ABBV-011 is a novel, SEZ6-directed ADC with preclinical antitumor activity in SCLC and other neuroendocrine cancers, Johnson says. ADCs are currently being investigated in both the first- and second-line settings in lung cancer, including in SCLC, Johnson notes.

A phase 1 first-in-human trial (NCT03639194) is evaluating ABBV-011 with or without the PD-1 inhibitor budigalimab in patients with SCLC. The primary end points of this trial are safety and the determination of the maximum tolerated dose and/or recommended phase 2 dose of the agent. Preliminary results from this trial’s monotherapy dose-escalation and -expansion cohorts were presented at the 2023 ASCO Annual Meeting. In this trial, patients who received ABBV-011 monotherapy had a confirmed overall response rate of 25%, including 10 partial responses, and the median duration of response was 4.2 months (95% CI, 2.6-6.7). Additionally, the clinical benefit rate was 65%, and the rate of clinical benefit lasting more than 12 weeks was 43%. Furthermore, patients achieved a median progression-free survival of 3.5 months. In total, 98% of patients experienced treatment-emergent adverse effects, including fatigue, nausea, thrombocytopenia, anorexia, and vomiting.

The payload for this ADC is calicheamicin, which can be difficult for patients to target, Johnson explains. However, these findings support the initiation of a parallel study targeting SEZ6 with a different payload, according to Johnson. The findings with ABBV-011 also indicate the broad potential for ADCs in the SCLC treatment landscape, since ADCs can be adjusted to better target specific tumors and become more tolerable for patients, Johnson emphasizes. SEZ6 is a new target for patients with SCLC that expands the treatment paradigm beyond DLL3-targeted agents, Johnson concludes.