AbbVie's ABBV-011 Shows Encouraging Antitumor Activity and Favorable Safety in Patients with Small Cell Lung Cancer

ABBV-011 Phase I Trial

At the 2023 ASCO Annual Meeting, AbbVie presented the findings from a Phase I trial (NCT03639194) evaluating ABBV-011 in patients with relapsed or refractory small-cell lung cancer (SCLC). The trial indicated that ABBV-011, an antibody-drug conjugate (ADC) targeting the seizure-related homolog protein (SEZ6), was well-tolerated and demonstrated antitumor activity in this patient population.

SEZ6 is a cell surface protein that is highly expressed in neuroendocrine tumors, including SCLC, as well as certain neuronal tissue while having minimal expression in most normal tissues. ABBV-011 consists of an anti-SEZ6 antibody linked to calicheamicin, a potent payload previously used in two ADC therapies, gemtuzumab ozogamicin, and inotuzumab ozogamicin, which are FDA-approved for hematologic malignancies.

The trial included sites in the United States, Japan, South Korea, and Taiwan. It involved 36 patients in the dose-escalation phase, with ongoing dose expansion (NCT03639194). In the dose-escalation phase, six different doses were tested, ranging from 0.3 mg/kg to 2.0 mg/kg every 3 weeks, as well as 0.5 mg/kg every week for 2 weeks with a 1-week break. The dose-expansion phase involved various dose levels, including a de-escalated dose of 1.6 mg/kg on the first cycle and 1.2 mg/kg in subsequent cycles. The trial aimed to identify the optimal dose, and additional cohorts were enrolled to further evaluate doses of 0.8 mg/kg and 1.0 mg/kg. Among the total cohort of 99 patients, 51% were female, and the median age was 63 years. A significant portion of patients had received prior lines of treatment, with varying numbers of prior treatments.

As of the data cutoff date in August 2022, the trial did not reach the maximum tolerated dose during the dose-limiting toxicity period of 6 weeks. However, late-onset toxicities, including elevated bilirubin and cytopenias, were observed beyond this period. Consequently, the trial investigators identified 1.0 mg/kg as the preliminary recommended Phase II dose due to its efficacy and tolerability. The Phase I trial is still assessing the efficacy and toxicity of patients who received the 0.8 mg/kg dose in the dose-expansion phase to determine the final recommended Phase II dose.

In terms of treatment-emergent adverse events (TEAEs), the entire trial cohort experienced TEAEs at a rate of 77%, while the rate among the 40 patients who received the 1.0 mg/kg dose in the dose-expansion phase was 78%.

A concerning toxicity associated with calicheamicin-based ADCs is veno-occlusive liver disease, which occurred in 2% of the total cohort and 3% of the dose-expansion cohort receiving 1.0 mg/kg, leading to treatment discontinuation. Notably, despite the increased SEZ6 expression in the brain, no central nervous system toxicity was observed during the trial.


1 mg/kg

(n = 40)


(n = 99)

Any TEAE, n (%)

39 (98%)

96 (97%)

Grade ≥3 TEAE, n (%)

26 (65%)

63 (64%)

Serious TEAEs, n (%)

18 (45%)

41 (41%)

Treatment-related AEs, n (%)

31 (78%)

76 (77%)

The objective response rate was 19% for the total cohort and 25% for the 1 mg/kg dose-expansion cohort. The clinical benefit rate (CBR), based on patients who had a partial response or stable disease was 69% and 65% for the total and 1 mg/kg dose-expansion cohorts, respectively. The CBR lasted more than 12 weeks for 37% and 43% of patients in the total and 1 mg/kg dose-expansion cohorts, respectively.

The median duration of response was 4.2 months for the 1 mg/kg dose-expansion cohort, and the median treatment duration was 12 weeks. The median progression-free survival for the dose-expansion cohort was 3.5 months. 

Efficacy Outcome


n = 98

Confirmed ORR, n (%)

19 (19%)

CBR, n (%)

68 (69%)

CBR lasting >12 weeks, n (%)

36 (37%)

KOL insights

“The properties of SEZ6 make it an appealing target. There are very few targets for antibody-drug conjugates in small cell lung cancer–Expert Opinion.

“This antibody-drug conjugate definitely has efficacy. The question is, what is the lowest effective dose, and who are the patients most likely to benefit from it? Will patients with higher SEZ6 expression have more benefit” –Expert Opinion.

“These data are still preliminary, but they suggest at this time there is an efficacy signal for this antibody-drug conjugate in small cell lung cancer, which is a very difficult disease with a limited number of treatment options” –Expert Opinion.


ABBV-011 exhibited good tolerability and demonstrated antitumor activity in a Phase I trial involving patients with relapsed or refractory SCLC. The trial also includes a cohort studying the combination of ABBV-011 with budigalimab, a PD-1 inhibitor, although these patients were not included in the current analysis.

The unique properties of SEZ6 make it an attractive target for therapy. This membrane protein is highly expressed in SCLC and other neuroendocrine tumors while showing minimal expression in most normal tissues. Therefore, it holds promise for further investigation. Currently, there are very few targets for antibody-drug conjugates in the context of SCLC, making ABBV-011 an important development in this field