Start Your Search
OA15 - Targeted Agents and Immunotherapy for Small Cell Lung Cancer (ID 152)
- Event: WCLC 2019
- Type: Oral Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:Raffaele Califano, Charles M Rudin
- Coordinates: 9/10/2019, 14:30 - 16:00, Hilton Head (1978)
OA15.01 - Combination Olaparib and Temozolomide in Relapsed Small Cell Lung Cancer: Updated Results from Phase 1/2 Clinical Trial (Now Available) (ID 1394)
14:30 - 16:00 | Author(s): Beow Yeap
DNA damage repair inhibition is an emerging strategy for treating small cell lung cancer (SCLC). Combining poly(ADP-ribose) polymerase (PARP) inhibition with the DNA alkylating agent temozolomide has shown activity in both preclinical models and early phase clinical trials.Method
This is a single-arm phase 1/2 study combining the PARP inhibitior olaparib (tablet formulation) with temozolomide in patients with SCLC. Key eligibility criteria include histologically or cytologically confirmed incurable SCLC which progressed following ≥ 1 platinum-based chemotherapy. In cohort 1, olaparib and temozolomide are administered orally on days 1-7 of 21-day cycles. After cohort 1 completed enrollment, cohort 2 was added in a protocol amendment, in which olaparib is administered continuously days 1-21 and temozolomide is administered days 1-7 of 21-day cycles. For each cohort, the phase 1 portion is a conventional 3+3 design, with the primary objective to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). The primary objective of the phase 2 dose expansion portion is to determine the objective response rate (ORR). Response assessments are performed every 6 weeks, with treatment continued until progression, unacceptable toxicity, or investigator’s discretion. Treatment post-progression is allowed for patients with ongoing clinical benefit.Result
Between October 2015 and April 2018, 50 patients were enrolled to cohort 1. The median age was 63 (range 39-85), median number of prior therapies was 2 (range 1-7), and 72% were platinum sensitive. The RP2D was olaparib 200 mg PO BID d1-7 and T 75 mg/m2 QD d1-7. The confirmed ORR was 41.7%. After a median follow-up of 7.1 months among 22 surviving patients, the median progression-free survival (mPFS) was 4.2 months, median overall survival (mOS) was 8.5 months, and median duration of response (mDoR) was 4.3 months. The ORR among platinum-sensitive and platinum-resistant patients was 47.1% and 28.6%, respectively, with no significant differences in mPFS, mOS or mDOR. The most common grade 3/4 treatment related adverse events were neutropenia (38%), anemia (28%) and thrombocytopenia (26%). Among 41 pts treated at the RP2D, dose reductions occurred in 44% overall and 64% of those who received at least 3 cycles. Enrollment to the phase 1 portion of cohort 2 began in November 2018 and is ongoing. Updated results from cohorts 1 and 2 will be presented at the meeting.Conclusion
Combination olaparib and temozolomide has an acceptable tolerability profile and shows promising clinical activity in relapsed SCLC. Clinical trials identifier NCT02446704.
Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.