NCT04401995

Study of TLR9 Agonist Vidutolimod (CMP-001) in Combination with Nivolumab Vs. Nivolumab

Randomized Neoadjuvant Pilot Phase II Study of TLR9 Agonist Vidutolimod (CMP-001) in Combination with Nivolumab Vs. Nivolumab in Stage IIIB/C/D Melanoma Patients with an Integrated Imaging Biomarker

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Diwakar Davar · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main goal of this research study is to determine how nivolumab and nivolumab/Vidutolimod (CMP-001) combination affect the likelihood of destroying melanoma involving lymph node and/or in-transit/satellite areas. The main goal of the PET/CT scan with 18F\]F-AraG is to evaluate how \[18F\]F-AraG uptake changes before and after administration of either nivolumab or nivolumab/CMP-001 combination.

Detailed description

This is a phase II pilot study designed to compare the pCR rate of two neoadjuvant immunotherapies in high-risk resectable melanoma with two integrated biomarkers. The integrated \[18F\]F-AraG imaging biomarker images activated CD8+ T cells. The CD8+ T cell density biomarker quantitates CD8+ T Cells using an automated method. The primary purpose of the study is to describe the correlation between pCR and the distribution of either biomarkers in patients receiving either neoadjuvant Vidutolimod (CMP-001)/nivolumab or neoadjuvant nivolumab. Patients with stage IIIB-IIID cutaneous (or unknown primary) melanoma with palpable nodal disease who have yet to undergo definitive surgery are eligible to enroll. Patients with nodal 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. Patients will undergo biopsies of both planned injected and uninjected lesions (Arm A) and target lesion (Arm B). Biopsies of these lesions will occur pre-treatment, at W3 or W4 and the target 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. 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). \[18F\]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 (W2). 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 Screening and W2 imaging timepoints, following \[18F\]F-AraG injection, a 30-min static PET-CT scan will be performed covering the brain to the upper legs. For CD8+ T cell density assessments, patients will undergo biopsies at 2 timepoints: pre-treatment (Screening) and on-treatment (W3 or W4). In Arm A, patients will undergo biopsies of planned injected and a 2nd uninjected lesion. At each imaging timepoint, biopsies will be performed. 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 480mg IV q4 x12 along with Vidutolimod (CMP-001) 5mg SC q4 x12 over a 48 week period; while patients randomized to Arm B (neoadjuvant Nivolumab) will receive Nivolumab (480mg IV q4 x12 over a 48 week period). In the post-operative period, CMP-001 will be administered subcutaneously (Arm A only).

Conditions

• Melanoma

Interventions

Type	Name	Description
DRUG	Vidutolimod (CMP-001)	A molecule comprised of a 30 nucleotide strand, flanked by 10 guanines on either end. The nucleotide strand is surrounded by a Qβ viral-like protein. The intended mechanism of action of CMP-001 in oncology is the activation of TLR9 in pDC within the tumor or the tumor-draining lymph nodes (tumor-associated pDC).
BIOLOGICAL	Nivolumab	a fully human Ig G4 antibody that blocks PD-1. Nivolumab was initially approved by the FDA for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Nivolumab has also been FDA approved to treat patients with advanced squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy, as well as advanced renal cell carcinoma.
OTHER	[18F]F-AraG PET/CT	\[18F\]F-AraG is an 18F-labeled analog of arabinofuranosylguanine (AraG), a compound that has shown remarkably selective accumulation in T cells. It has several advantages over conventional \[18F\] and existing small molecule PET agents being investigated for immuno-monitoring. \[18F\]F-AraG has lower accumulation and more efficient efflux from cancer cells than a dCK agent.

Timeline

• Start date: 2020-09-02
• Primary completion: 2024-08-16
• Completion: 2024-08-16
• First posted: 2020-05-26
• Last updated: 2024-10-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study