NCI10066: A Phase 1/2 Study of Olaparib in Combination With Ramucirumab in Previously Treated Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma

Authors

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

Publication Date

2-1-2024

Journal

British Journal of Cancer

DOI

10.1038/s41416-023-02534-1

PMID

38135713

PMCID

PMC10844282

PubMedCentral® Posted Date

12-22-2023

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Ramucirumab, Stomach Neoplasms, Phthalazines, Adenocarcinoma, Esophagogastric Junction, Antineoplastic Combined Chemotherapy Protocols, Esophageal Neoplasms, Piperazines

Published Open-Access

yes

Recommended Citation

Cecchini, Michael; Cleary, James M; Shyr, Yu; et al., "NCI10066: A Phase 1/2 Study of Olaparib in Combination With Ramucirumab in Previously Treated Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma" (2024). Faculty, Staff and Student Publications. 4584.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4584