(1) Morgensztern D (2) Ready N (3) Johnson ML (4) Dowlati A (5) Choudhury N (6) Carbone DP (7) Schaefer E (8) Arnold SM (9) Puri S (10) Piotrowska Z (11) Hegde A (12) Chiang AC (13) Iams W (14) Tolcher A (15) Nosaki K (16) Kozuki T (17) Li T (18) Santana-Davila R (19) Akamatsu H (20) Murakami H (21) Yokouchi H (22) Wang S (23) Zha J (24) Li R (25) Robinson RR (26) Hingorani P (27) Jeng EE (28) Furqan M
In a phase 1 clinical trial, Morgensztern et al. evaluated escalating doses of ABBV-011 – an antibody–drug conjugate targeting SEZ6 and delivering a payload of calicheamicin – in 99 patients with SEZ6+ SCLC. With a median of 3 treatment cycles, the ORR was 19%. At the tentative RP2D, the ORR was 25%, the median DOR was 4.2 months, and the median PFS was 3.5 months. Patients treated as a second-line therapy and who had a longer chemo-free interval prior to treatment saw better results. ABBV-01 was well tolerated, in line with other calicheamicin-based ADCs. There was no evidence of toxicity in the eyes or brain, where SEZ6 is also expressed.
Contributed by Lauren Hitchings
(1) Morgensztern D (2) Ready N (3) Johnson ML (4) Dowlati A (5) Choudhury N (6) Carbone DP (7) Schaefer E (8) Arnold SM (9) Puri S (10) Piotrowska Z (11) Hegde A (12) Chiang AC (13) Iams W (14) Tolcher A (15) Nosaki K (16) Kozuki T (17) Li T (18) Santana-Davila R (19) Akamatsu H (20) Murakami H (21) Yokouchi H (22) Wang S (23) Zha J (24) Li R (25) Robinson RR (26) Hingorani P (27) Jeng EE (28) Furqan M
In a phase 1 clinical trial, Morgensztern et al. evaluated escalating doses of ABBV-011 – an antibody–drug conjugate targeting SEZ6 and delivering a payload of calicheamicin – in 99 patients with SEZ6+ SCLC. With a median of 3 treatment cycles, the ORR was 19%. At the tentative RP2D, the ORR was 25%, the median DOR was 4.2 months, and the median PFS was 3.5 months. Patients treated as a second-line therapy and who had a longer chemo-free interval prior to treatment saw better results. ABBV-01 was well tolerated, in line with other calicheamicin-based ADCs. There was no evidence of toxicity in the eyes or brain, where SEZ6 is also expressed.
Contributed by Lauren Hitchings
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 (Q3W) during dose escalation (0.3-2 mg/kg) and expansion. Patients with SEZ6-positive tumors (³25% of tumor cells with ³1+ staining intensity by immunohistochemistry) 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]); median age was 63 years (range, 41-79). Thirty-two percent, 41%, and 26% of patients received 1, 2, and ³3 prior therapies, respectively. The maximum tolerated dose was not reached through 2.0 mg/kg. Most common treatment-emergent adverse events (TEAEs) were fatigue (50%), nausea (42%), and thrombocytopenia (41%). Most common hepatic TEAEs were increased aspartate aminotransferase (22%), increased g-glutamyltransferase (21%), and hyperbilirubinemia (17%); 2 patients experienced veno-occlusive liver disease. Objective response rate (ORR) was 19% (19/98). In the 1-mg/kg dose-expansion cohort (n=40), ORR was 25%; median response duration was 4.2 months (95% CI, 2.6-6.7) and median progression-free survival was 3.5 months (95% CI, 1.5-4.2). CONCLUSIONS: ABBV-011 1.0 mg/kg Q3W 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.
Author Info: (1) Washington University in St. Louis, St. Louis, MO, United States. (2) Duke Medical Center, Durham, NC, United States. (3) Sarah Cannon Research Instutite, Nashville, TN, United
Author Info: (1) Washington University in St. Louis, St. Louis, MO, United States. (2) Duke Medical Center, Durham, NC, United States. (3) Sarah Cannon Research Instutite, Nashville, TN, United States. (4) University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States. (5) Memorial Sloan Kettering Cancer Center, New York, NY, United States. (6) The Ohio State University Medical Center, Columbus, OH, United States. (7) Highlands Oncology Group, Fayetteville, AR, United States. (8) University of Kentucky, Lexington, KY, United States. (9) Huntsman Cancer Institute, Salt Lake City, Utah, United States. (10) Massachusetts General Hospital, Boston, Massachusetts, United States. (11) University of Alabama at Birmingham, Birmingham, Alabama, United States. (12) Yale University, New Haven, CT, United States. (13) Northwestern Memorial Hospital, Nashville, TN, United States. (14) South Texas Accelerated Research Therapeutics, San Antonio, TX, United States. (15) National Cancer Center Hospital East, Kashiwa, Chiba, Japan. (16) National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. (17) University of California, Davis, Sacramento, United States. (18) Fred Hutchinson/University of Washington/Seattle Children's Cancer Consortium, Seattle, United States. (19) Wakayama Medical University, Wakayama, Japan. (20) Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan. (21) NHO Hokkaido Cancer Center, Sapporo, Japan. (22) AbbVie Inc., North Chicago, Illinois, United States. (23) AbbVie, North Chicago, Illinois, United States. (24) AbbVie Inc., North Chicago, Illinois, United States. (25) AbbVie Inc., South San Francisco, CA, United States. (26) AbbVie (United States), United States. (27) AbbVie (United States), North Chicago, Illinois, United States. (28) University of Iowa, Iowa city, Iowa, United States.
Citation: Clin Cancer Res 2024 Sep 17 Epub09/17/2024
