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David E. Kanamori
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P2.12 - Small Cell Lung Cancer/NET (ID 180)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.12-09 - Phase 2 Study of Talazoparib Plus Low-Dose Temozolomide in Patients with Relapsed/Refractory Extensive-Stage Small Cell Lung Cancer (ID 954)
10:15 - 18:15 | Author(s): David E. Kanamori
- Abstract
Background
Talazoparib exhibits cytotoxic effects by inhibiting poly (ADP-ribose) polymerase (PARP) proteins 1 and 2 in addition to “trapping” PARP on DNA. Temozolomide (TMZ) has been shown to increase antitumor response when combined with a PARP inhibitor in small cell lung cancer (SCLC) models (Wainberg AACR 2016). Combining PARP inhibition with TMZ as second-line therapy for ES-SCLC may improve disease-related outcomes.
Method
This is a phase 2, open-label, single-arm study of the safety and efficacy of talazoparib plus TMZ in patients with extensive-stage SCLC. The primary endpoint is objective response rate (ORR) based on RECIST 1.1 criteria. Secondary endpoints include progression-free survival, overall survival, duration of response, and time to response. Exploratory endpoints include biomarker studies such as DNA damage response gene analysis and patient reported outcomes (PRO).
Participants are required to have relapsed (progressed within 6 months) or refractory (progressed
during or within 4 weeks of completing 1stline platinum-based regimen) ES-SCLC. Those with a best response of progressive disease to first-line therapy per RECIST 1.1 or more than one line of cytotoxic therapy are excluded. Prior immunotherapy is allowed. Participants receive talazoparib 0.75 mg po daily on 28-day cycles with TMZ 37.5 mg/m2 po on days 1-5. 15 participants will be enrolled in the first part of a Simon two-stage design; if 3 or more responses are seen, an additional 13 participants will be enrolled. The null hypothesis will be rejected if 8 or more objective responses are observed compared to a historical control of 15% ORR in second-line topotecan (Horita Sci Rep 2015).
Result
As of 8 March 2019, 3 participants were evaluable for treatment response. Median age was 51 (range 46-80). One participant had a confirmed partial response (PR) with 50% reduction in target lesions, one had stable disease with 16% reduction in target lesions, and one had progressive disease (PD). Biomarker and PRO analysis correlated with the radiographic response. In the participant with PR, Guardant circulating tumor DNA testing showed PIK3CA amplification and TP53 mutations at baseline that were not detectable at week 5 of treatment, whereas the other subjects has persistent ctDNA. Patient-reported outcomes similarly noted improvement in the participant with PR within 2 weeks while the one with PD showed no improvement throughout treatment course. Adverse events were hematologic, including one grade 4 thrombocytopenia that resolved within 2 weeks.
Conclusion
Combination talazoparib and TMZ used as second-line therapy in ES-SCLC is tolerable and has shown promising preliminary results. The trial will continue to enroll. Updated response and biomarker data will be presented.