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

• Sponsor: Diwakar Davar (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03618641
• Collaborator: Checkmate Pharmaceuticals (Industry)
• Enrollment: 34
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 54.7
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Melanoma; Lymph Node Cancer	Drug: CMP-001; Biological: Nivolumab	Phase 2

Detailed Description

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 Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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: Aug 8, 2018
• Actual Primary Completion Date: Aug 20, 2020
• Anticipated Study Completion Date: Mar 1, 2023

Arms and Interventions

Arm

Intervention/Treatment

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.

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

Outcome Measures

Primary Outcome Measures

1. Major Pathologic Response Rate (MPR) [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%).

Secondary Outcome Measures

1. Radiographic Response Rate [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.

2. Relapse-Free Survival (RFS) [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.

3. 6-month Relapse-free Survival [Up to 6 months]

   Probability that patients did not experience disease relapse, 6-months post start of treatment.

4. 12-month Relapse-free Survival [Up to 12 months]

   Probability that patients did not experience disease relapse, 12 months post treatment.

5. 24-month Relapse-free Survival [Up to 24 months]

   Probability that patients did not experience disease relapse, 24-months post start of treatment.

6. Overall Survival (OS) [Up to 31 months]

   The length of time from the start of treatment that patients remain alive.

7. 6-month Overall Survival (OS) [Up to 31 months]

   The probability that patients remain alive.

8. 12-month Overall Survival (OS) [Up to 31 months]

   The probability that patients remain alive.

9. 24-month Overall Survival (OS) [Up to 31 months]

   The probability that patients remain alive.

Other Outcome Measures

1. Expression of Inhibitory and Activating Receptors and Ligands [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.

2. TCR Clonality/Diversity Analyses of Circulating and Intra-tumoral CD8+ T-cells [3 years]

   TCR clonality/diversity will be compared pre and post nivolumab and CMP-001 combination treatment.

3. Genetic and Transcriptomic Signatures of Response/Non-response [3 years]

   Genetic and transcriptomic signatures will be compared between patients who do and do not respond to study treatment.

4. Novel Tumor Imaging Characteristics in Responders and Non-responders [3 years]

   Tumor imaging characteristics will be compared between patients who do and do not respond to study treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Be willing and able to provide written informed consent for the study.

2. Be ≥ 18 years of age on day of signing informed consent.

3. Diagnosis of histologically or cytologically confirmed diagnosis of cutaneous melanoma belonging to one of the following AJCC TNM stages:

4. Tx or T1-4 and

5. N1b, or N1c, or N2b, or N2c, or N3b, or N3c and

6. M0

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.

1. Presence of injectable and measureable disease based on RECIST 1.1.

2. 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.

3. Performance status of 0 or 1 on the ECOG Performance Scale.

4. Demonstrate adequate organ function as defined below performed on screening labs obtained within 4 weeks of registration.

• Absolute neutrophil count (ANC) ≥1,500 /mcL

• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L

• Platelets ≥100,000 / mcL

• Serum creatinine or Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN.

• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN.

• AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN.

• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.

• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.

1. Female subject of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

2. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 26 weeks after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.

3. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 26 weeks after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria:

1. History of uveal or mucosal melanoma.

2. 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.

3. 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.

4. 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.

1. Active (i.e., symptomatic or growing) central nervous system (CNS) metastases.

2. 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.

3. 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.

4. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

5. Has an active infection requiring systemic therapy.

6. 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.

7. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

8. 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.

9. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137. Prior treatment with ipilimumab or interferon alfa is allowed. Patients with history of allergic or hypersensitivity reaction to interferon alfa or ipilimumab are also excluded.

10. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

11. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected. Patients with treated Hepatitis B/C with no evidence of active infection may be enrolled.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• Diwakar Davar
• Checkmate Pharmaceuticals

Investigators

• Principal Investigator: Diwakar Davar, MD, University of Pittsburgh Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 3, 2020

More Information

Publications

None provided.

• Responsible Party: Diwakar Davar, Assistant Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT03618641
• Other Study ID Numbers: 17-169
• First Posted: Aug 7, 2018
• Last Update Posted: Apr 5, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Diwakar Davar, Assistant Professor, University of Pittsburgh: Stage IIIB/C/D
• Additional relevant MeSH terms: Melanoma; Nivolumab

Study Results

Participant Flow

Arm/Group Title	Nivolumab and CMP-001 Combination
Arm/Group Description	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.
Period Title: Overall Study
STARTED	34
COMPLETED	34
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Nivolumab and CMP-001 Combination
Arm/Group Description	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.
Overall Participants	34
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	64.5
Sex: Female, Male (Count of Participants)
Female	15 44.1%
Male	19 55.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	34 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Disease Stage (Count of Participants)
Stage IIIB	15 44.1%
Stage IIIC	16 47.1%
Stage IIID	3 8.8%

Outcome Measures

1. Primary Outcome

Title	Major Pathologic Response Rate (MPR)
Description	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%).
Time Frame	Every 6 weeks from start of study treatment, up to 52 weeks

Outcome Measure Data

Analysis Population Description

Patients who completed pre-operative therapy and receive surgery were evaluable for MPR; patients who did not undergo surgery for reasons of disease progression precluding surgery (rapid disease progression) were not evaluable

Arm/Group Title	Nivolumab and CMP-001 Combination
Arm/Group Description	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.
Measure Participants	30
pCR (0% RVT)	14 41.2%
pMR (0%< RVT ≤10%)	3 8.8%
pPR (10%< RVT ≤50)	3 8.8%
pNR (RVT >50%)	10 29.4%

2. Secondary Outcome

Title	Radiographic Response Rate
Description	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.
Time Frame	Up to 31 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Relapse-Free Survival (RFS)
Description	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.
Time Frame	Up to 31 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	6-month Relapse-free Survival
Description	Probability that patients did not experience disease relapse, 6-months post start of treatment.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	12-month Relapse-free Survival
Description	Probability that patients did not experience disease relapse, 12 months post treatment.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	24-month Relapse-free Survival
Description	Probability that patients did not experience disease relapse, 24-months post start of treatment.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Overall Survival (OS)
Description	The length of time from the start of treatment that patients remain alive.
Time Frame	Up to 31 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	6-month Overall Survival (OS)
Description	The probability that patients remain alive.
Time Frame	Up to 31 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	12-month Overall Survival (OS)
Description	The probability that patients remain alive.
Time Frame	Up to 31 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	24-month Overall Survival (OS)
Description	The probability that patients remain alive.
Time Frame	Up to 31 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Other Pre-specified Outcome

Title	Expression of Inhibitory and Activating Receptors and Ligands
Description	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.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Other Pre-specified Outcome

Title	TCR Clonality/Diversity Analyses of Circulating and Intra-tumoral CD8+ T-cells
Description	TCR clonality/diversity will be compared pre and post nivolumab and CMP-001 combination treatment.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	Genetic and Transcriptomic Signatures of Response/Non-response
Description	Genetic and transcriptomic signatures will be compared between patients who do and do not respond to study treatment.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Other Pre-specified Outcome

Title	Novel Tumor Imaging Characteristics in Responders and Non-responders
Description	Tumor imaging characteristics will be compared between patients who do and do not respond to study treatment.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse Events monitored up to 31 months, All-Cause Mortality monitored up to 31 months
Adverse Event Reporting Description	Adverse Events: Grade 1 and Grade 2 events per CTCAE v4.0 Serious Adverse Events: Grade 3 and Grade 4 events per CTCAE v4.0
Arm/Group Title	Nivolumab and CMP-001 Combination
Arm/Group Description	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.
All Cause Mortality
	Nivolumab and CMP-001 Combination
	Affected / at Risk (%)	# Events
Total	9/34 (26.5%)
Serious Adverse Events
	Nivolumab and CMP-001 Combination
	Affected / at Risk (%)	# Events
Total	6/34 (17.6%)
Cardiac disorders
Restrictive cardiomyopathy	1/34 (2.9%)
General disorders
General disorders and administration site conditions - Other, specify	1/34 (2.9%)
Immune system disorders
Immune system disorders - Other, specify	1/34 (2.9%)
Infections and infestations
Soft tissue infection	1/34 (2.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/34 (2.9%)
Vascular disorders
Thromboembolic event	1/34 (2.9%)
Other (Not Including Serious) Adverse Events
	Nivolumab and CMP-001 Combination
	Affected / at Risk (%)	# Events
Total	34/34 (100%)
Blood and lymphatic system disorders
Anemia	13/34 (38.2%)
Blood and lymphatic system disorders - Other, specify	3/34 (8.8%)
Cardiac disorders
Cardiac disorders - Other, specify	1/34 (2.9%)
Sinus bradycardia	5/34 (14.7%)
Sinus tachycardia	6/34 (17.6%)
Endocrine disorders
Adrenal insufficiency	1/34 (2.9%)
Endocrine disorders - Other, specify	1/34 (2.9%)
Hypothyroidism	1/34 (2.9%)
Eye disorders
Blurred vision	2/34 (5.9%)
Eye disorders - Other, specify	2/34 (5.9%)
Flashing lights	1/34 (2.9%)
Floaters	1/34 (2.9%)
Gastrointestinal disorders
Colonic obstruction	1/34 (2.9%)
Constipation	3/34 (8.8%)
Diarrhea	10/34 (29.4%)
Dry mouth	1/34 (2.9%)
Dyspepsia	1/34 (2.9%)
Gastritis	1/34 (2.9%)
Hemorrhoids	1/34 (2.9%)
Mucositis oral	3/34 (8.8%)
Nausea	12/34 (35.3%)
Oral pain	1/34 (2.9%)
Vomiting	7/34 (20.6%)
General disorders
Chills	22/34 (64.7%)
Edema face	1/34 (2.9%)
Edema limbs	5/34 (14.7%)
Fatigue	18/34 (52.9%)
Fever	19/34 (55.9%)
Flu like symptoms	2/34 (5.9%)
General disorders and administration site conditions - Other, specify	9/34 (26.5%)
Infusion related reaction	3/34 (8.8%)
Injection site reaction	9/34 (26.5%)
Malaise	1/34 (2.9%)
Neck edema	1/34 (2.9%)
Pain	7/34 (20.6%)
Immune system disorders
Cytokine release syndrome	4/34 (11.8%)
Infections and infestations
Infections and infestations - Other, specify	6/34 (17.6%)
Joint infection	1/34 (2.9%)
Lung infection	0/34 (0%)
Sinusitis	1/34 (2.9%)
Soft tissue infection	0/34 (0%)
Upper respiratory infection	2/34 (5.9%)
Vaginal infection	1/34 (2.9%)
Wound infection	2/34 (5.9%)
Injury, poisoning and procedural complications
Fall	1/34 (2.9%)
Injury, poisoning and procedural complications - Other, specify	2/34 (5.9%)
Radiation recall reaction (dermatologic)	1/34 (2.9%)
Seroma	2/34 (5.9%)
Investigations
Activated partial thromboplastin time prolonged	2/34 (5.9%)
Alanine aminotransferase increased	4/34 (11.8%)
Alkaline phosphatase increased	3/34 (8.8%)
Aspartate aminotransferase increased	4/34 (11.8%)
Blood bilirubin increased	2/34 (5.9%)
Cardiac troponin I increased	1/34 (2.9%)
Creatinine increased	3/34 (8.8%)
INR increased	1/34 (2.9%)
Investigations - Other, specify	28/34 (82.4%)
Lymphocyte count decreased	5/34 (14.7%)
Neutrophil count decreased	8/34 (23.5%)
Platelet count decreased	8/34 (23.5%)
Weight gain	2/34 (5.9%)
Weight loss	2/34 (5.9%)
White blood cell decreased	6/34 (17.6%)
Metabolism and nutrition disorders
Anorexia	5/34 (14.7%)
Hyperglycemia	6/34 (17.6%)
Hyperkalemia	3/34 (8.8%)
Hypermagnesemia	7/34 (20.6%)
Hypernatremia	1/34 (2.9%)
Hyperuricemia	7/34 (20.6%)
Hypoalbuminemia	9/34 (26.5%)
Hypocalcemia	6/34 (17.6%)
Hypoglycemia	2/34 (5.9%)
Hypokalemia	7/34 (20.6%)
Hypomagnesemia	5/34 (14.7%)
Hyponatremia	22/34 (64.7%)
Hypophosphatemia	10/34 (29.4%)
Metabolism and nutrition disorders - Other, specify	4/34 (11.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/34 (20.6%)
Arthritis	1/34 (2.9%)
Back pain	6/34 (17.6%)
Generalized muscle weakness	1/34 (2.9%)
Muscle weakness upper limb	1/34 (2.9%)
Musculoskeletal and connective tissue disorder - Other, specify	10/34 (29.4%)
Myalgia	1/34 (2.9%)
Myositis	1/34 (2.9%)
Neck pain	2/34 (5.9%)
Pain in extremity	5/34 (14.7%)
Nervous system disorders
Dizziness	2/34 (5.9%)
Dysgeusia	1/34 (2.9%)
Headache	8/34 (23.5%)
Movements involuntary	1/34 (2.9%)
Nervous system disorders - Other, specify	3/34 (8.8%)
Paresthesia	1/34 (2.9%)
Peripheral motor neuropathy	1/34 (2.9%)
Peripheral sensory neuropathy	1/34 (2.9%)
Syncope	1/34 (2.9%)
Tremor	1/34 (2.9%)
Psychiatric disorders
Anxiety	3/34 (8.8%)
Confusion	1/34 (2.9%)
Depression	1/34 (2.9%)
Insomnia	5/34 (14.7%)
Renal and urinary disorders
Hematuria	7/34 (20.6%)
Proteinuria	7/34 (20.6%)
Renal and urinary disorders - Other, specify	3/34 (8.8%)
Urinary tract pain	1/34 (2.9%)
Urine discoloration	1/34 (2.9%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/34 (2.9%)
Cough	3/34 (8.8%)
Dyspnea	3/34 (8.8%)
Hypoxia	1/34 (2.9%)
Nasal congestion	1/34 (2.9%)
Pneumonitis	1/34 (2.9%)
Postnasal drip	2/34 (5.9%)
Respiratory, thoracic and mediastinal disorders - Other, specify	1/34 (2.9%)
Sore throat	2/34 (5.9%)
Skin and subcutaneous tissue disorders
Alopecia	1/34 (2.9%)
Erythema multiforme	1/34 (2.9%)
Photosensitivity	1/34 (2.9%)
Pruritus	5/34 (14.7%)
Rash acneiform	1/34 (2.9%)
Rash maculo-papular	4/34 (11.8%)
Skin and subcutaneous tissue disorders - Other, specify	9/34 (26.5%)
Skin hypopigmentation	1/34 (2.9%)
Surgical and medical procedures
Surgical and medical procedures - Other, specify	0/34 (0%)
Vascular disorders
Flushing	2/34 (5.9%)
Hematoma	1/34 (2.9%)
Hypertension	12/34 (35.3%)
Hypotension	3/34 (8.8%)
Lymphedema	1/34 (2.9%)
Thromboembolic event	1/34 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.