NCT03993626

A Trial of CXD101 in Combination With Nivolumab in Patients With Metastatic Microsatellite-Stable Colorectal Cancer

A Phase Ib/ II Trial to Assess the Safety and Efficacy of CXD101 in Combination With the PD-1 Inhibitor Nivolumab in Patients With Metastatic, Previously-Treated, Microsatellite-Stable Colorectal Carcinoma

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 55 (actual)
• Sponsor: Celleron Therapeutics Ltd. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a study to assess the safety and efficacy of CXD101 in combination with the PD-1 Inhibitor Nivolumab in patients with metastatic, previously-treated, Microsatellite-Stable (MSS) Colorectal Carcinoma (CRC). The primary hypothesis of this study is that CXD101 and anti-PD1 monoclonal antibody synergise the anti-tumour activity in MSS colorectal cancer patients (\~95% of CRC) who do not seem to respond to anti-PD1 or -PD-L1 immunotherapy alone.

Detailed description

Phase Ib trial: This single-arm dose escalation trial will determine the safety, tolerability and dose limiting toxicities (DLT) and therefore the maximum tolerated dose (MTD) of repeat doses of nivolumab combined with CXD101. The incidence and severity of adverse events (evaluated according to CTCAE version 4.03), vital signs, ECG parameters, biochemistry, haematology and urinalysis will be recorded to determine tolerability. Dose escalation will proceed as follows: Dose Level 1 Nivolumab 240 mg iv q 2 weekly; with CXD101 30 mg (20mg mane, 10mg nocte) po for 5 days q 3 weekly (n=3-6) with both drugs commencing on the same day in cycle 1. Dose Level 2 Nivolumab 240 mg iv q 2 weekly; with CXD101 40mg (20 mg bid) po for 5 days q 3 weekly (n=6) with both drugs commencing on the same day in cycle 1. A maximum of 15 subjects will be required. Phase II trial: Following completion of the Phase Ib study, a Phase II CXD101/ nivolumab combination dose will be selected by the Data and Safety Monitoring Committee. Up to a further 40 subjects will then be treated at the selected Phase II CXD101/ nivolumab combination dose. Subjects may continue to receive CXD101/ nivolumab until complete response, disease progression, unacceptable toxicity, withdrawal of consent, or other medical problems supervene. Efficacy will be measured using Immune Response Evaluation Criteria in Solid Tumours (iRECIST) Imaging studies, typically CT scan of chest, abdomen \& pelvis, supplemented by MRI of liver when required, will be performed at Baseline and after every 6 weeks, with objective confirmation of response 6 weeks (+/- 1 week) after observation. Safety parameters will be assessed as in the Phase I study. In addition there will be a series of translational analyses including correlation of tumour biomarker expression with response.

Conditions

• Colorectal Neoplasms Malignant

Interventions

Type	Name	Description
DRUG	CXD101 in Combination With Nivolumab	HDAC inhibitor in combination with anti-PD-1 monoclonal antibody

Timeline

• Start date: 2018-05-22
• Primary completion: 2019-12-15
• Completion: 2020-06-15
• First posted: 2019-06-21
• Last updated: 2019-06-21

Locations

1 site across 1 country: United Kingdom