Related Experiment Video
Updated: Jun 9, 2026
Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
Phase I/II study of AT-101 with topotecan in relapsed and refractory small cell lung cancer
Rebecca Suk Heist1, Jerry Fain, Bernard Chinnasami
1Massachusetts General Hospital, Boston, Massachusetts 02114, USA. rheist@partners.org
Introduction:
AT-101 is an oral, pan Bcl-2 family protein inhibitor that has demonstrated activity in small cell lung cancer (SCLC) models. A phase I/II study was conducted combining AT-101 with topotecan in relapsed and refractory SCLC.
Methods:
An open-labeled multicenter phase I/II study was conducted of oral AT-101 with intravenous topotecan in patients with SCLC who had progressed on prior platinum-containing chemotherapy. The phase II portion was a two-stage design, and two cohorts of patients, sensitive relapsed and refractory, were analyzed. Primary endpoint in the two-stage phase II portion was response rate; secondary endpoints were duration of response and time to progression.
Results:
Thirty-six patients were enrolled. The most common toxicities were hematologic, as would be expected with topotecan and AT-101. The recommended phase II dose was 40 mg AT-101 days 1 to 5 with topotecan 1.25 mg/m(2) days 1 to 5 on a 21-day cycle. In the sensitive-relapsed cohort (n = 18), there were 0 complete response (CR), three partial response (PR), 10 stable disease (SD), and four progressive disease (PD). In the refractory cohort (n = 12), there were 0 CR/PR, five SD, and five PD. The study did not meet its prespecified endpoints to continue enrollment in the second stage of the phase II study. Median time to progression in the sensitive-relapsed cohort was 17.4 weeks and 11.7 weeks in the refractory cohort.
Conclusions:
AT-101 can be safely combined with topotecan at a reduced dose of 1.25 mg/m(2). The response rates observed did not meet the criteria for additional enrollment; however, many patients had a best response of SD and the median time to progression in both cohorts was favorable. Additional trials of AT-101 in SCLC are ongoing.
Insights
This study combined AT-101 with topotecan for small cell lung cancer (SCLC). While response rates were low, the combination was safe and showed favorable time to progression in relapsed/refractory SCLC patients.
Area of Science:
- Oncology
- Pharmacology
Background:
- AT-101 is an oral pan-Bcl-2 inhibitor with prior activity in small cell lung cancer (SCLC) models.
- A phase I/II study investigated combining AT-101 with topotecan in SCLC.
Purpose of the Study:
- To evaluate the safety and efficacy of combining AT-101 with topotecan in patients with relapsed and refractory SCLC.
- To determine the recommended phase II dose for this combination therapy.
Main Methods:
- An open-label, multicenter phase I/II study.
- Two patient cohorts: sensitive relapsed and refractory SCLC.
- Primary endpoint: response rate; secondary endpoints: duration of response and time to progression.
Main Results:
- The recommended phase II dose was AT-101 40 mg (days 1-5) with topotecan 1.25 mg/m² (days 1-5) every 21 days.
- Hematologic toxicities were the most common adverse events.
- The study did not meet prespecified response rate endpoints for further enrollment, but showed stable disease in many patients.
Conclusions:
- AT-101 can be safely combined with topotecan at a reduced dose.
- Although response rates were below criteria, favorable median time to progression was observed.
- Further clinical trials of AT-101 in SCLC are warranted.
Related Concept Videos
02:56Treatment Resistent Cancers
02:56Treatment Resistant Cancers
01:11Clinical Trials: Overview