CMP-001 in Combo With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease

NCT03618641 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-169
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose this research study is to determine if the combination of nivolumab and CMP-001 improves the likelihood of eradicating (destroying) disease in the lymph node (pathologic response rate).

Conditions

Melanoma; Lymph Node Cancer

Keywords

Stage IIIB/C/D

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response Rate (MPR)

  Distribution of pathologic response in the 30 evaluable patients. Major pathologic response was defined on surgical specimens analyzed by blinded two independent dermatopathologists using immune related pathologic response criteria (irPRC). Residual viable tumor (RVT) (wherein RVT = viable tumor area/total tumor bed area) was calculated depending on the quantity of viable malignant cells on H\&E-stained slides and confirmatory SOX-10-stained representative sections in ambiguous cases; and thresholds defined as follows: complete response (pCR, 0% RVT), major response (pMR, 0%\< RVT ≤10%), partial response (pPR, 10%\< RVT ≤50%), and pNR (RVT \>50%).

  Every 6 weeks from start of study treatment, up to 52 weeks

Secondary Outcomes (9)

• Radiographic Response Rate

  Up to 31 months

• Relapse-Free Survival (RFS)

  Up to 31 months

• 6-month Relapse-free Survival

  Up to 6 months

• 12-month Relapse-free Survival

  Up to 12 months

• 24-month Relapse-free Survival

  Up to 24 months

Other Outcomes (4)

• Expression of Inhibitory and Activating Receptors and Ligands

  3 years

• TCR Clonality/Diversity Analyses of Circulating and Intra-tumoral CD8+ T-cells

  3 years

• Genetic and Transcriptomic Signatures of Response/Non-response

  3 years

Study Arms (1)

Nivolumab and CMP-001 Combination

EXPERIMENTAL

Prime Phase -Nivolumab 240mg, IV Infusion, every two weeks starting with Cycle 2 ( Cycles 2, 4, 6) for 6 weeks in combination with CMP-001, 5mg, Injection, at Week 1 and the remaining injections, 10 mg will be administered Weeks 2 -7. Boost Phase -Nivolumab 240mg, IV Infusion, every two weeks, over a 46 week period in combination with CMP-001, 5mg, administered every 4 weeks for 1 year.

Drug: CMP-001; Biological: Nivolumab

Interventions

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 CMP-001 Combination

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 (metastatic) squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy, as well as advanced renal cell carcinoma.

Nivolumab and CMP-001 Combination

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.
• 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 and/or in-transit metastasis; or at the time of clinical detected nodal and/or in-transit 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 or without regional lymph node involved permitted if considered potentially surgically resectable at baseline.
• NOTE: Determination of potential resectability must be made at baseline to be eligible for this neoadjuvant study.
• NOTE: Patients with mucosal and/or uveal melanoma are not permitted to enroll. Patients with melanomas of unknown primary may be enrolled at the discretion of the treating investigator in discussion with Principal Investigator.
• Presence of injectable and measureable disease based on RECIST 1.1.
• Willing to undergo tumor biopsy (core, punch, incisional or excisional). Patients must undergo biopsy (core, punch) or open biopsy (incisional, excisional) within 4 weeks of registration on the 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

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (2)

• Davar D, Morrison RM, Dzutsev AK, Karunamurthy A, Chauvin JM, Amatore F, Deutsch JS, Das Neves RX, Rodrigues RR, McCulloch JA, Wang H, Hartman DJ, Badger JH, Fernandes MR, Bai Y, Sun J, Cole AM, Aggarwal P, Fang JR, Deitrick C, Bao R, Duvvuri U, Sridharan SS, Kim SW, A Choudry H, Holtzman MP, Pingpank JF, O'Toole JP, DeBlasio R, Jin Y, Ding Q, Gao W, Groetsch C, Pagliano O, Rose A, Urban C, Singh J, Divarkar P, Mauro D, Bobilev D, Wooldridge J, Krieg AM, Fury MG, Whiteaker JR, Zhao L, Paulovich AG, Najjar YG, Luke JJ, Kirkwood JM, Taube JM, Park HJ, Trinchieri G, Zarour HM. Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial. Cancer Cell. 2024 Nov 11;42(11):1898-1918.e12. doi: 10.1016/j.ccell.2024.10.007. Epub 2024 Oct 31.

  PMID: 39486411 RESULT

• Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.

  PMID: 36648215 DERIVED

Related Links

• Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial

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

Results Point of Contact

• Title: Barbara Stadterman, MPH, MCCR; CRS Regulatory Supervisor
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

412-647-5554

Study Officials

• Diwakar Davar, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 7, 2018
• Study Start: August 8, 2018
• Primary Completion: August 20, 2020
• Study Completion: December 31, 2023
• Last Updated: May 14, 2025
• Results First Posted: September 16, 2021

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)