TY - JOUR
T1 - A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6-Targeting Antibody-Drug Conjugate, in Patients with Small Cell Lung Cancer
AU - Morgensztern, Daniel
AU - Ready, Neal
AU - Johnson, Melissa L.
AU - Dowlati, Afshin
AU - Choudhury, Noura
AU - Carbone, David P.
AU - Schaefer, Eric
AU - Arnold, Susanne M.
AU - Puri, Sonam
AU - Piotrowska, Zofia
AU - Hegde, Aparna
AU - Chiang, Anne C.
AU - Iams, Wade
AU - Tolcher, Anthony
AU - Nosaki, Kaname
AU - Kozuki, Toshiyuki
AU - Li, Tianhong
AU - Santana-Davila, Rafael
AU - Akamatsu, Hiroaki
AU - Murakami, Haruyasu
AU - Yokouchi, Hiroshi
AU - Wang, Song
AU - Zha, Jiuhong
AU - Li, Rui
AU - Robinson, Randy R.
AU - Hingorani, Pooja
AU - Jeng, Edwin E.
AU - Furqan, Muhammad
N1 - Publisher Copyright:
© 2024 The Authors.
PY - 2024/11/15
Y1 - 2024/11/15
N2 - Purpose: Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/ refractory SCLC. We report initial outcomes of ABBV-011 monotherapy. Patients and Methods: ABBV-011 was administered intravenously once every 3 weeks during dose escalation (0.3-2 mg/kg) and expansion. Patients with SEZ6-positive tumors (≥25% of tumor cells with ≥1+ staining intensity by IHC) were preselected for expansion. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated. Results: As of August 2022, 99 patients received ABBV-011 monotherapy [dose escalation, n = 36; Japanese dose evaluation, n = 3; dose expansion, n = 60 (1 mg/kg, n = 40)]; the median age was 63 years (range, 41-79 years). Also, 32%, 41%, and 26% of patients received 1, 2, and ≥3 prior therapies, respectively. The maximum tolerated dose was not reached through 2.0 mg/kg. The most common treatment-emergent adverse events were fatigue (50%), nausea (42%), and thrombocytopenia (41%). The most common hepatic treatment-emergent adverse events were increased aspartate aminotransferase (22%), increased γ-glutamyltransferase (21%), and hyperbilirubinemia (17%); two patients experienced veno-occlusive liver disease. The objective response rate was 19% (19/98). In the 1-mg/kg dose-expansion cohort (n = 40), the objective response rate was 25%; the median response duration was 4.2 months (95% confidence interval, 2.6- 6.7); and the median progression-free survival was 3.5 months (95% confidence interval, 1.5-4.2). Conclusions: ABBV-011 1.0 mg/kg every 3 weeks monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/ refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.
AB - Purpose: Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/ refractory SCLC. We report initial outcomes of ABBV-011 monotherapy. Patients and Methods: ABBV-011 was administered intravenously once every 3 weeks during dose escalation (0.3-2 mg/kg) and expansion. Patients with SEZ6-positive tumors (≥25% of tumor cells with ≥1+ staining intensity by IHC) were preselected for expansion. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated. Results: As of August 2022, 99 patients received ABBV-011 monotherapy [dose escalation, n = 36; Japanese dose evaluation, n = 3; dose expansion, n = 60 (1 mg/kg, n = 40)]; the median age was 63 years (range, 41-79 years). Also, 32%, 41%, and 26% of patients received 1, 2, and ≥3 prior therapies, respectively. The maximum tolerated dose was not reached through 2.0 mg/kg. The most common treatment-emergent adverse events were fatigue (50%), nausea (42%), and thrombocytopenia (41%). The most common hepatic treatment-emergent adverse events were increased aspartate aminotransferase (22%), increased γ-glutamyltransferase (21%), and hyperbilirubinemia (17%); two patients experienced veno-occlusive liver disease. The objective response rate was 19% (19/98). In the 1-mg/kg dose-expansion cohort (n = 40), the objective response rate was 25%; the median response duration was 4.2 months (95% confidence interval, 2.6- 6.7); and the median progression-free survival was 3.5 months (95% confidence interval, 1.5-4.2). Conclusions: ABBV-011 1.0 mg/kg every 3 weeks monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/ refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.
UR - https://www.scopus.com/pages/publications/85209828507
U2 - 10.1158/1078-0432.CCR-24-1547
DO - 10.1158/1078-0432.CCR-24-1547
M3 - Article
C2 - 39287821
AN - SCOPUS:85209828507
SN - 1078-0432
VL - 30
SP - 5042
EP - 5052
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 22
ER -