KEY TAKEAWAYS
- The SOLID phase II trial aimed to evaluate the safety and efficacy of olaparib and durvalumab in IDH-mutated cholangiocarcinoma pts.
- The primary objective was to measure ORR. Secondary objectives include PFS, ORR, and safety.
- The study found olaparib and durvalumab were well-tolerated but ineffective. IDH1/2 mutations may not cause BRCAness, and further studies are planned.
IDH1/2 mutations are found in 25% of cholangiocarcinomas (CCAs) and cause the accumulation of R-2-hydroxyglutarate(R2HG), which impairs DNA repair. This suggests that IDH1/2 mutant tumors may be sensitive to PARP inhibitors. PARP inhibition also increases the expression of PD-L1, so combining a PARP inhibitor and an immune checkpoint inhibitor may be synergistic.
Researchers aimed to evaluate the safety and efficacy of olaparib and durvalumab in patients(pts) with IDH-mutated cholangiocarcinoma.
Pts continuously received olaparib 300 mg twice daily and durvalumab 1500 mg IV every 4 weeks. The study followed Simon’s optimal two-stage design, with an interim analysis for efficacy. The initial stage included 10 pts, with plans for expansion if ≥2 responses were observed. The primary objective was to determine the overall response rate(ORR) (RECIST 1.1) and disease control rate (DCR). Secondary objectives included progression-free survival(PFS), overall survival(OS), and assessing the safety of the olaparib and durvalumab combination.
About 10 pts with IDH1m were enrolled in this study. Their median age was 63.5 years (range 49-78), and 50% were female. All pts had a baseline ECOG PS of 0-1, 40% of the pts had prior surgical resections followed by recurrent disease, and 20% had undergone ≥2 lines of prior chemotherapy, with 90% receiving prior platinum therapy.
The median duration of treatment was 1.95 months (range 1.8-13.5). There were no treatment-related grade 3-4 toxicities. Any grade toxicities included fatigue (100%), nausea (60%), anemia (20%), hypothyroidism (20%), and elevated liver enzymes (20%). No complete or partial responses were observed. The DCR was 30%, with 3 pts demonstrating stable disease. One patient remained on treatment for 13.5 months and was eventually taken off the study due to clinical progression. The median PFS was 1.97 months (95% CI 1.73-3.93). Given that no responses were seen in the initial 10 pts, the study did not proceed to Stage 2.
The study found olaparib and durvalumab were well-tolerated but ineffective. IDH1/2 mutations may not cause BRCAness, and further studies are planned.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.4099
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03991832
Erica S. Tsang, Grainne M. O’Kane, Jennifer J. Knox, and Eric X Chen. DOI: 10.1200/JCO.2023.41.16_suppl.4099 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 4099-4099.
