A Phase Ib Dose-Escalation Study of LCL161 Plus Oral Topotecan for Patients With Relapsed/Refractory Small Cell Lung Cancer and Select Gynecologic Malignancies

• Published in: The oncologist (Dayton, Ohio) Vol. 28; no. 7; pp. 640 - e559
• Main Authors: Johnson, Melissa L, Patel, Manish R, Aljumaily, Raid, Jones, Suzanne F, Burris, III, Howard A, Spigel, David R
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-07-2023
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Cancer; Care and treatment; Chemotherapy, Combination; Clinical Trial Results; Development and progression; Diagnosis; Dosage and administration; Drug therapy; Drug therapy, Combination; Female; Genital cancer; Genital Neoplasms, Female; Health aspects; Humans; Lung cancer, Small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Oncology, Experimental; Ovarian cancer; Patient outcomes; Pharmaceutical industry; Small Cell Lung Carcinoma - drug therapy; Testing; Topotecan - adverse effects; Women; United Kingdom; France; United States; Switzerland; Tennessee; Germany; gynecologic malignancies; relapsed/refractory disease; Smac mimetic; small cell lung cancer; topotecan
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1093/oncolo/oyad029

Abstract
Background
This was an open-label, multicenter, single-arm phase Ib dose-escalation study of oral LCL161 administered in combination with oral topotecan in patients with relapsed/refractory small cell lung cancer (SCLC) and select gynecological cancers.
Methods
Cohorts of 3-6 patients initiated treatment with LCL161 and topotecan in escalating doses. LCL161 was administered orally on days 1, 8, and 15 of each 21-day cycle; topotecan was administered orally for the first 5 days of each 21-day cycle.
Results
A total of 35 patients were enrolled in 6 cohorts; 30 patients were female; 4 patients had SCLC and 19 patients had ovarian cancer. Median prior lines of therapy were 3 (1-10). Median duration of treatment was 7.1 weeks (0.1-174). The most frequent grade 3/4 treatment-related adverse events were thrombocytopenia (51.43%) and anemia (31.43%). ORR was 9.7%; 58% of patients had SD. The study was stopped early before the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) were determined.
Conclusion
The addition of LCL161 to oral topotecan caused more myelosuppression when dosed together than what was associated with either drug alone. Moreover, the drug combination did not improve outcomes. The study was terminated early (ClinicalTrials.gov Identifier: NCT02649673).
This article reports the results of a clinical trial of oral LCL161 administered in combination with oral topotecan in patients with relapsed/refractory small cell lung cancer and select gynecological cancers.