NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma

Author:

Cecchini MichaelORCID,Cleary James M.,Shyr Yu,Chao Joseph,Uboha Nataliya,Cho May,Shields Anthony,Pant Shubham,Goff Laura,Spencer Kristen,Kim EdwardORCID,Stein Stacey,Kortmansky Jeremy S.,Canosa Sandra,Sklar Jeffrey,Swisher Elizabeth M.,Radke Marc,Ivy Percy,Boerner Scott,Durecki Diane E.,Hsu Chih-Yuan,LoRusso Patricia,Lacy Jill

Abstract

Abstract Background Our preclinical work revealed tumour hypoxia induces homologous recombination deficiency (HRD), increasing sensitivity to Poly (ADP-ribose) polymerase inhibitors. We aimed to induce tumour hypoxia with ramucirumab thereby sensitising tumours to olaparib. Patients and methods This multi-institution single-arm Phase 1/2 trial enrolled patients with metastatic gastroesophageal adenocarcinoma refractory to ≥1 systemic treatment. In dose escalation, olaparib was evaluated at escalating dose levels with ramucirumab 8 mg/kg day 1 in 14-day cycles. The primary endpoint of Phase 1 was the recommended Phase 2 dose (RP2D), and in Phase 2 the primary endpoint was the overall response rate (ORR). Results Fifty-one patients received ramucirumab and olaparib. The RP2D was olaparib 300 mg twice daily with ramucirumab 8 mg/kg. In evaluable patients at the RP2D the ORR was 6/43 (14%) (95% CI 4.7–25.6). The median progression-free survival (PFS) was 2.8 months (95% CI 2.3–4.2) and median overall survival (OS) was 7.3 months (95% CI 5.7–13.0). Non-statistically significant improvements in PFS and OS were observed for patients with tumours with mutations in HRD genes. Conclusions Olaparib and ramucirumab is well-tolerated with efficacy that exceeds historical controls with ramucirumab single agent for gastric cancer in a heavily pre-treated patient population.

Funder

U.S. Department of Health & Human Services | NIH | National Cancer Institute

Conquer Cancer Foundation

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Oncology

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