Therapeutic Targeting of ATR Yields Durable Regressions in High Replication Stress Tumors

Patients were enrolled on an investigator-initiated, single-arm, phase 2 trial (NCT02487095) conducted at the Center for Cancer Research, National Cancer Institute (NCI) in Bethesda, MD. This trial was approved by the NCI institutional review board and conducted per Good Clinical Practice guidelines, defined by the International Conference on Harmonization. All patients provided written informed consent per Declaration of Helsinki principles. Patients were eligible if they were aged 18 years or older and had histologically confirmed SCLC; measurable, progressing disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1), and an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less. Eligible patients had at least one line of chemotherapy. Patients also had to have adequate renal, liver, and bone marrow function. Patients with symptomatic brain metastases were excluded from trial although patients who have had treatment for their brain metastasis and whose brain disease was stable without steroid therapy for 1 week were eligible. Before initiating therapy, we required patients to have at least 2 weeks without previous chemotherapy or major surgery and 24 hours without radiation.]]>
The study was phase I/II clinical trial. Phase I part was conducted between Between September 2016 and February 2017, and determined recommended dose for phase II part. The result was previously reported (Thomas A., et al. J Clin Oncol. 2018 Jun 1;36(16):1594-1602. PMID: 29252124) We subsequently conducted phase II part and enrolled 26 patients with small cell lung cancer and 10 patients with extrapulmonary small cell cancers, between July 2017 to March 2020.]]>