CMP-001 in Combo With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease
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|ClinicalTrials.gov Identifier: NCT03618641|
Recruitment Status : Active, not recruiting
First Posted : August 7, 2018
Results First Posted : September 16, 2021
Last Update Posted : April 5, 2022
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Lymph Node Cancer||Drug: CMP-001 Biological: Nivolumab||Phase 2|
Patients are being asked to take part in this clinical research study because they have stage IIIB, IIIC or IIID cutaneous (or unknown primary) melanoma with lymph node disease and have yet to undergo surgery. There are two phases, Prime Phase and a Boost Phase. If they participate they will receive nivolumab in combination with CMP-001 for a total of 7 weeks (Prime Phase) prior to surgery. Surgery will be performed approximately 2-4 weeks after completion of the Prime Phase. After recovery from surgery patients will receive additional nivolumab in combination with CMP-001 for approximately 46 additional weeks (Boost Phase).
The main goal of this research study to determine if the combination of nivolumab and CMP-001 improves the likelihood of eradicating (destroying) disease in the lymph node (pathologic response rate). Pathologic responses are associated with improved relapse-free and overall survival in melanoma.
Prior to surgery (Prime Phase) Nivolumab 240mg, will be administered as a 30-minute IV infusion on an outpatient basis. During the Prime Phase, 3 cycles of Nivolumab will be administered every 2 weeks over a 6 week period starting with cycle 2, cycle 4 and then cycle 6.
Prior to surgery (Prime Phase) CMP-001 will be given as an injection from a syringe weekly for a total of 7 weeks. The first injection (week 1), 5mg, will be applied directly into the skin and the remaining injections, 10mg will be administered, will be given intra-tumorally for weeks 2-7.
Surgery will be performed to the cancerous lymph node 2-4 weeks after the Prime Phase is completed.
After recovery from surgery (Boost Phase) Nivolumab will be administered at 240mg every 2 weeks or 480 mg every 4 weeks depending on the physician's preference. CMP-001, 5mg, will be administered by injections intra-tumorally every 4 weeks for up to 54 weeks.
Patients will be followed to assess for survival status until death, withdrawal of consent, or the end of the study, whichever occurs first. This will be done every 3 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Neoadjuvant Phase II Study of TLR9 Agonist CMP-001 in Combination With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease|
|Actual Study Start Date :||August 8, 2018|
|Actual Primary Completion Date :||August 20, 2020|
|Estimated Study Completion Date :||March 2023|
Experimental: Nivolumab and CMP-001 Combination
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.
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).
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.
- Major Pathologic Response Rate (MPR) [ Time Frame: Every 6 weeks from start of study treatment, up to 52 weeks ]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%).
- Radiographic Response Rate [ Time Frame: Up to 31 months ]Complete response [CR], partial response [PR], stable disease, per RECIST v1.1 criteria. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to <10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
- Relapse-Free Survival (RFS) [ Time Frame: Up to 31 months ]Length of time from the initiation of treatment that patients survive without recurrence of disease. Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
- 6-month Relapse-free Survival [ Time Frame: Up to 6 months ]Probability that patients did not experience disease relapse, 6-months post start of treatment.
- 12-month Relapse-free Survival [ Time Frame: Up to 12 months ]Probability that patients did not experience disease relapse, 12 months post treatment.
- 24-month Relapse-free Survival [ Time Frame: Up to 24 months ]Probability that patients did not experience disease relapse, 24-months post start of treatment.
- Overall Survival (OS) [ Time Frame: Up to 31 months ]The length of time from the start of treatment that patients remain alive.
- 6-month Overall Survival (OS) [ Time Frame: Up to 31 months ]The probability that patients remain alive.
- 12-month Overall Survival (OS) [ Time Frame: Up to 31 months ]The probability that patients remain alive.
- 24-month Overall Survival (OS) [ Time Frame: Up to 31 months ]The probability that patients remain alive.
- Expression of Inhibitory and Activating Receptors and Ligands [ Time Frame: 3 years ]Circulating and intra-tumoral immune cells, including T-cells (CD8, CD4, Tregs) and antigen-presenting cells (monocytes, macrophages, MDSCs), will be compared pre and post nivolumab and CMP-001 combination treatment.
- TCR Clonality/Diversity Analyses of Circulating and Intra-tumoral CD8+ T-cells [ Time Frame: 3 years ]TCR clonality/diversity will be compared pre and post nivolumab and CMP-001 combination treatment.
- Genetic and Transcriptomic Signatures of Response/Non-response [ Time Frame: 3 years ]Genetic and transcriptomic signatures will be compared between patients who do and do not respond to study treatment.
- Novel Tumor Imaging Characteristics in Responders and Non-responders [ Time Frame: 3 years ]Tumor imaging characteristics will be compared between patients who do and do not respond to study treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03618641
|United States, Pennsylvania|
|UPMC Hillman Cancer Center|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Diwakar Davar, MD||University of Pittsburgh Medical Center|