CTIM-05 - Results of safety lead in of phase II trial of combination olaparib, temozolomide, and pembrolizumab for patients with IDH-mutant glioma

Friday, November 17, 2023

7:30 PM – 9:30 PM PT

Location: Exhibit Hall A/B

Poster Presenter(s)

John T. Fortunato

Memorial Sloan Kettering Cancer Center
New York, New York, United States

Author(s)

AN

Adam Newton

Memorial Sloan Kettering Cancer Center
New York, New York, United States
AG

Ashley Gonzalez

Memorial Sloan Kettering Cancer Center
New York, United States
IG

Igor Gavrilovic

Memorial Sloan Kettering Cancer Center
New York, New York, United States
Alexandra M. Miller

Memorial Sloan Kettering Cancer Center
New York, New York, United States
Christian Grommes

Memorial Sloan Kettering Cancer Center
New York, New York, United States
Andrew L. Lin

Memorial Sloan Kettering Cancer Center
New York, New York, United States
Elena Pentsova

Memorial Sloan Kettering Cancer Center
New York, New York, United States
Ingo K. Mellinghoff

Memorial Sloan Kettering Cancer Center
New York, New York, United States
TK

Thomas Kaley

Memorial Sloan Kettering Cancer Center
New York, United States
Lauren R. Schaff

Memorial Sloan Kettering Cancer Center
New York, New York, United States

Background: Recurrent gliomas are universally fatal with few adequate treatment options. IDH-mutant gliomas may be susceptible to PARP inhibition, thus combination therapy using alkylating agents and checkpoint inhibition could be synergistic.

Methods: This is an open label, phase II study of olaparib, temozolomide, and pembrolizumab for patients with recurrent IDH-mutant glioma, grade 2 or 3, with measurable enhancing disease per RANO. Patients received pembrolizumab 200mg IV on day 1 of each 21-day cycle. Oral olaparib 200mg twice daily and temozolomide 50mg/m2 daily were given days 1-7 of cycles 3-11. Here, we report the results of our safety lead in, consisting of the first 6 patients to complete cycle 3.

Results: A total of seven patients were enrolled to the safety lead-in: 2 women; 5 patients with astrocytoma, 2 oligodendroglioma. Patients had a median age of 45 (range 29-63) and median KPS 90 (range 80-100). Median number of recurrences was 3.5 (range 1-5). All had received prior alkylating therapy and all but 1 patient had received prior RT. No patients were taking steroids at the time of enrollment. Six patients completed the dose-limiting toxicity (DLT) period without any DLTs. One patient experienced clinical progression on pembrolizumab monotherapy prior to the start of combination therapy and was thus replaced. No grade 3 or 4 toxicities were seen through the DLT period. The most common clinical toxicities at least possibly related to treatment were grade 1 and 2 fatigue (n=4), nausea (n=3) and constipation (n=2). Hematological toxicities include grade 1 anemia (n=2) and decreased platelet count (n=1).

Conclusions: The combination of olaparib, temozolomide, and pembrolizumab was well tolerated in this cohort. Following completion of the safety lead-in, the trial was redesigned to minimize the length of pembrolizumab monotherapy and introduce combination therapy in cycle 1. Enrollment is ongoing. NCT05188508.