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

NCT04401995 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: HCC 20-049
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Melanoma

Keywords

residual volume of tumor (RVT); standard uptake value (SUV)

Outcome Measures

Primary Outcomes (3)

• Major Pathologic Response Rate (MPR)

  A ratio of responders (to treatment) to total number of tumors (responders plus non-responders to treatment). Immune-related pathologic response rate based on the percent (%) of residual volume of tumor (RVT). Pathologic Non Response (pNR) is defined as %RVT\>50%; Partial Pathologic Response (pPR) is defined as 10%\< %RVT\<50% (at least 10%, up to 49%); Major Pathologic Response (MPR) is defined as %RVT≤10%; Pathologic

  At the time of surgery (Week 8-10)

• Pathologic Complete Response (pCR) Rate

  Per Immune-related pathologic response criteria (irPRC), pCR is defined as 0% RVT remaining in post-therapy specimen.

  At the time of surgery (Week 8-10)

• Distant-metastasis free survival (DMFS)

  The length of time from initiation of treatment until distant-metastasis of melanoma or death.

  At 6-months, 12-months, 2-year, 3-year, 5-year; up to 5 years

Secondary Outcomes (4)

• Tumor PET response via [18F]F-AraG

  At Week 1 (baseline) and Week 5

• Relapse-Free Survival (RFS)

  At 6-months, 12-months, 2-year, 3-year, 5-year; up to 5 years

• Overall Survival (OS)

  At 6-month, 12-months, 2-year, 3-year, 5-year; up to 5 years

• Adverse Events at Least Possibly Related to Study Treatment

  Up to 5 years

Other Outcomes (1)

• CD8+ T cell density

  Pre-treatment (Screening), at Week 3 of treatment; up to 21 days

Study Arms (2)

Nivolumab and Vidutolimod (CMP-001) Combination with [18F]F-AraG PET/CT

EXPERIMENTAL

Prime Phase - Nivolumab 240mg IV, every 2 weeks starting with Cycle 2 (Cycles 2,4,6) for 6 weeks in combination with Vidutolimod 5mg subcutaneous 1st dose, and the remaining injections, 10mg intra-tumorally will be administered Weeks 2-7. \[18F\]F-AraG PET/CT, single bolus injection of 5 (±10%) mCi IV into a vein, Screening and at Week 2. Boost Phase - Nivolumab 480mg IV, every 4 weeks and CMP-001 5mg subcutaneous every 4 weeks up to 48 weeks.

Drug: Vidutolimod (CMP-001); Biological: Nivolumab; Other: [18F]F-AraG PET/CT

Nivolumab with [18F]F-AraG PET/CT

EXPERIMENTAL

Prime Phase - Nivolumab 240mg IV, every 2 weeks starting with Cycle 2 (Cycles 2, 4, 6) for 6 weeks. \[18F\]F-AraG PET/CT, single bolus injection of 5 (±10%) mCi IV into a vein, Screening and at Week 3. Boost Phase - Nivolumab 480mg IV, every 4 weeks starting from the time of surgery recovery for up to 48 weeks.

Biological: Nivolumab; Other: [18F]F-AraG PET/CT

Interventions

Vidutolimod (CMP-001) DRUG

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).

Nivolumab and Vidutolimod (CMP-001) Combination with [18F]F-AraG PET/CT

Nivolumab BIOLOGICAL

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.

Nivolumab and Vidutolimod (CMP-001) Combination with [18F]F-AraG PET/CT; Nivolumab with [18F]F-AraG PET/CT

[18F]F-AraG PET/CT OTHER

\[18F\]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.

Nivolumab and Vidutolimod (CMP-001) Combination with [18F]F-AraG PET/CT; Nivolumab with [18F]F-AraG PET/CT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the study.
• Be ≥ 18 years of age on day of signing informed consent.
• Willingness to undergo \[18F\]F-AraG PET imaging at pre- and week 3 timepoints.
• Diagnosis of histologically or cytologically confirmed diagnosis of cutaneous melanoma belonging to one of the following AJCC TNM stages:
• Tx or T1-4 and
• N1b, or N1c, or N2b, or N2c, or N3b, or N3c and
• Patients are eligible for this trial either at presentation for primary melanoma with concurrent regional nodal metastasis; or at the time of clinical detected nodal recurrence; and may belong to any of the following groups:
• Primary cutaneous melanoma with clinically apparent regional lymph node metastases.
• Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin.
• Clinically detected primary cutaneous melanoma involving multiple regional nodal groups.
• Clinical detected nodal melanoma (if single site) arising from an unknown primary.
• In-transit and/or satellite metastases with regional lymph node involved permitted if considered potentially surgically resectable at baseline.
• NOTE: Patients whose sole site of disease is regional lymph node involvement of the parotid LN basin are not eligible for this neoadjuvant study.
• NOTE: Patients with only in-transit and/or satellite metastases without regional lymph node involvement are not eligible for this neoadjuvant study.
• NOTE: Determination of potential resectability must be made at baseline to be eligible for this neoadjuvant study.

You may not qualify if:

• History of uveal or mucosal melanoma.
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Note: Subjects with autoimmune disorders of Grade 4 while on prior immunotherapy will be excluded. Subjects who developed autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤1 and the subject has been off systemic steroids at doses \>10 mg/d for at least 2 weeks.
• Active (i.e., symptomatic or growing) central nervous system (CNS) metastases.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has a systemic disease that requires systemic pharmacologic doses of corticosteroids greater than 10mg daily prednisone (or equivalent). Subjects who are currently receiving steroids at a dose of ≤10mg daily do not need to discontinue steroids prior to enrollment Subjects that require topical, ophthalmologic and inhalational steroids would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study. Subjects who require active immunosuppression (greater than steroid dose discussed above) for any reason are excluded.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 26 weeks after the last dose of trial treatment.

Sponsors & Collaborators

• Diwakar Davar: lead
• Checkmate Pharmaceuticals: collaborator
• CellSight Technologies, Inc.: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Diwakar Davar, MD, M.Sc

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: May 18, 2020
• First Posted: May 26, 2020
• Study Start: September 2, 2020
• Primary Completion: August 16, 2024
• Study Completion: August 16, 2024
• Last Updated: October 21, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)