NCT03085849

SGI-110 Plus Durvalumab/Tremelimumab in SCLC

A Phase I Study Evaluating the Safety and Efficacy of SGI-110 Followed by Combined Durvalumab Plus Tremelimumab in Subjects With Extensive-stage Small Cell Lung Cancer (ES-SCLC)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Catherine Shu · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine if a combination of investigational agents is safe to give to people with small cell lung cancer (SCLC) after standard chemotherapy has been attempted. Subjects enrolled in this trial will receive 3 investigational drugs: SGI-110 (guadecitabine), durvalumab (MEDI4736) and tremelimumab.

Detailed description

SCLC accounts for approximately 15% of new cases of lung cancer, and an estimated 33,000 cases are expected to be diagnosed in the United States in 2016. Compared to NSCLC, SCLC typically has a more rapid doubling time, a higher growth fraction, and earlier development of distant metastases. Patients with limited stage (LS) disease are treated with curative intent using definitive, concurrent chemotherapy and thoracic radiotherapy. For patients with extensive stage (ES) disease, systemic chemotherapy can prolong survival in most cases, however long-term survival is rare. Despite the activity of several agents in SCLC, an etoposide plus platinum (i.e. cisplatin) doublet regimen remains the standard of care in the first-line setting because of its higher activity compared to other chemotherapy regimens, as well as the ease of combining it with radiation. Initial response rates may be as high as 70-90% in LS-SCLC and 50-70% in ES-SCLC. However, the disease typically recurs rapidly which is reflected by median survival rates of 9 to 11 months for ES-SCLC and a 2-year survival rate of less than 5%. This study has a 3 + 3 design that will be used to assess the safety of SGI-110 given prior to flat doses of durvalumab (1500 mg) and tremelimumab (75 mg). The starting dose of SGI-110 will be 30 mg/m2 (dose level 0) and the target dose that is predicted to be safe and most effective will be 45 mg/m2 (dose level 1). These doses have been chosen based on safety and efficacy data from phase 1 clinical trials in other solid tumors, as described above. Patients enrolled in any given dose level will be evaluated for safety (adverse events monitoring) and efficacy. There will be mandatory pre- and on-treatment tumor biopsies performed in alternating fashion on cycle 1 day 8 +/- 2 days or cycle 2 day 8 +/- 2 days. The dose-limiting toxicity (DLT) observation period will last for 4 weeks (28 days) and ends on C2D1. Delayed serious immune-mediated adverse events will also be monitored but will not be considered dose limiting toxicities.

Conditions

• Extensive-stage Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Durvalumab	1500 mg IV on day 8 (flat dose) until progression
DRUG	Tremelimumab	75 mg IV on day 8 (flat dose) x 4 doses
DRUG	SGI-110	SC daily for 5 days (days 1-5) until progression or toxicity Dose escalation scheme: Dose level -1 - SGI-110 20 mg/m2 SC daily; Dose level 0 - SGI-110 30 mg/m2 SC daily; Dose level 1 - SGI-110 45 mg/m2 SC daily; and SGI-110 given on days 1-5 of every 28 day cycle

Timeline

• Start date: 2017-12-15
• Primary completion: 2018-11-26
• Completion: 2018-11-26
• First posted: 2017-03-21
• Last updated: 2018-12-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study