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J. Delord
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P1.15 - SCLC/Neuroendocrine Tumors (ID 701)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.15-004 - An Open-Label, Multitumor Phase II Basket Study of Olaparib and Durvalumab (MEDIOLA): Results in Patients with Relapsed SCLC (ID 9388)
09:30 - 09:30 | Author(s): J. Delord
- Abstract
Background:
The prognosis of small cell lung cancer (SCLC) remains poor and there is a high unmet need for effective therapies. Poly (ADP-ribose) polymerase (PARP) inhibitors and immunotherapies hold promise due to expression of PARP and high mutational burden in SCLC. PARP inhibition leads to upregulation of anti-programmed cell death ligand-1 (PD-L1) and enhanced cancer immunosuppression. This led us to investigate the combination of olaparib and the PD-L1 inhibitor, durvalumab in SCLC (NCT02734004).
Method:
Individuals with relapsed SCLC at least 12 weeks after platinum-based therapy were eligible. Patients received olaparib tablets 300 mg PO BID for a 4-week run-in, followed by a combination of olaparib 300 mg PO BID and durvalumab 1.5 g IV q 4 weeks. The combination was continued until progressive disease by RECIST 1.1. Tumor assessments were done at baseline, 4 weeks and every 8 weeks thereafter. The primary endpoints were disease control rate (DCR) at 12 weeks, as well as safety and tolerability. The secondary endpoints included DCR at 28 weeks, objective response rate (ORR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Biomarker endpoints included PD-L1 expression and evaluation of tumor infiltrating lymphocytes (TILs). A target DCR of 60% was used to calculate the sample size in a Bayesian predictive probability design.
Result:
Among the 38 patients, the median age was 63 years (range 44-76) and median line of prior chemotherapies 1 (range 1-3). At the time of analysis, each patient was followed up for at least 12 weeks. The most common grade 3 or higher AEs included anemia (34.2%), hyponatremia (10.5%), lymphopenia (10.5%), chronic obstructive pulmonary disease (5.3%), increased GGT (5.3%) and increased lipase (5.3%). DCR at 12 weeks was 29%. Confirmed responses included one partial response and one complete response. Three additional patients had unconfirmed responses. The updated primary and secondary endpoints, as well as biomarker and PK data will be presented.
Conclusion:
Although AEs of all grades were seen commonly, the combination of olaparib and durvalumab was relatively well tolerated, as most of the AEs were attributed to underlying disease. While efficacy of the combination in this SCLC population did not reach the target DCR and is below the futility boundary (<40%), a minority of patients obtained significant benefit and will be followed up for further clinical and translational analyses.
