Study of TLR9 Agonist CMP-001 in Combination With Nivolumab vs. Nivolumab

Summary

Participation Requirements

Description

This is a phase II pilot study comparing MPR rate between two neoadjuvant. This study is designed to evaluate a neoadjuvant regimen [nivolumab in combination with Toll-like receptor 9 (TLR9) agonist CMP-001] of 20 patients as compared against nivolumab monotherapy. This study includes an integrated ...

This is a phase II pilot study comparing MPR rate between two neoadjuvant. This study is designed to evaluate a neoadjuvant regimen [nivolumab in combination with Toll-like receptor 9 (TLR9) agonist CMP-001] of 20 patients as compared against nivolumab monotherapy. This study includes an integrated [18F]F-AraG imaging biomarker that aims assess the imaging biomarker in patients receiving either neoadjuvant CMP-001/nivolumab or neoadjuvant nivolumab. Patients with stage IIIB-IIID cutaneous (or unknown primary) melanoma with palpable nodal disease and/or in-transit disease who have yet to undergo definitive surgery are eligible to enroll. Patients with nodal and/or in-transit relapse including those who have received prior adjuvant IFN and/or ipilimumab are eligible to enroll. Suitable patients will be identified pre-operatively. Patients will undergo a 28 day screening evaluation including surgical assessment, clinical assessment, systemic/CNS staging scans, and laboratory studies to confirm suitability. Biopsies will occur pre-treatment, W4-5 and the injected lesion(s) will be resected at the time of surgery. Eligible patients will be randomized 1:1 to receive Arm A (neoadjuvant Nivolumab/CMP) vs. Arm B (neoadjuvant Nivolumab) during the (Prime Phase) pre-operatively for 6-7 weeks. Patients randomized to Arm A will receive: Nivolumab 240mg IV q2 x3 and CMP-001 5mg SC 1st dose then 10mg IT 2nd-7th doses (7 weeks). Patients randomized to Arm B will receive: Nivolumab 240mg IV q2 x3 (6 weeks). In the Prime Phase, CMP-001 will be administered weekly via sub-cutaneous injection (5mg SC; week 1) then intra-tumorally (10mg IT; weeks 2-7). [18F]F-AraG PET-CT scan (18-F PET) is an integrated biomarker and will be performed at 2 imaging time-points: pre-treatment (pre-W1) and on-treatment (W4). At each imaging timepoint, [18F]F-AraG will be administered by a licensed nuclear medicine technologist under the supervision of a nuclear medicine physician on an outpatient basis. Each patient will receive a single bolus injection of 5 mCi [18F]F-AraG IV into a hand or arm vein. At pre-W1/W4 imaging timepoints, following [18F]F-AraG injection, a 30-min static PET-CT scan will be performed covering the brain to the upper legs. Following the Prime Phase and restaging systemic scans, patients will undergo surgical resection. Post-operatively, patients will continue to receive maintenance therapy (Boost Phase) per randomization. In the Boost Phase, patients randomized to Arm A (neoadjuvant Nivolumab/CMP) will receive Nivolumab and CMP (480mg IV q4 x12; CMP-001 5mg SC q4 x12; 48 weeks); while patients randomized to Arm B (neoadjuvant Nivolumab) will receive Nivolumab (480mg IV q4 x12; 48 weeks). In the post-operative period, CMP-001 will be administered subcutaneously.

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