Melanoma
Conditions
Keywords
melanoma, skin
Brief summary
This study is to find out if the combination of CC-122 (an investigational agent) and Nivolumab will enhance the anti-cancer activity and prevent T-cell exhaustion (T-cells are responsible for maintaining the body's immune response).
Interventions
DRUGCC-122
Oral CC-122 at 2 mg daily, 5 days out of 7
DRUGNivolumab
240 mg Nivolumab intravenously days 1 and 15 in each 28 day cycle
Sponsors
Bristol-Myers Squibb
Celgene Corporation
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unresectable or metastatic melanoma of cutaneous, mucosal, conjunctival, or unknown origin. Uveal melanoma is not permitted. Cohort 1: Naïve to anti-PD1 therapy Cohort 2: Progressed on previous anti-PD1 therapy. Subjects who have received anti-PD1 therapy in the adjuvant setting for previously resected melanoma are eligible for this cohort provided they have not received any intervening systemic therapy for the relapse * Be willing and able to provide written informed consent for the trial. * Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 * Females of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. * Females 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 28 days after last dose of avadomide or 5 months after the last dose of nivolumab, whichever is longer. Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \>1 year. * Males should agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of avadomide or 7 months after last dose of nivolumab, whichever is longer. * Adequate organ function
Exclusion criteria
* Has received an investigational drug or other anti-cancer therapy within 3 weeks of the first dose of treatment or \< 5 half-lives of that agent, whichever is shorter. Any toxicity from prior therapy must have recovered to \< grade 1. * 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 (only exception to this is the need for steroids for CNS metastases; see #6 below). Inhaled, intra-articular, or topical steroids are permissible. * Has a history of hypersensitivity to nivolumab. * Has a known additional malignancy that is progressing or requires active treatment, the lack of which would pose a risk to the health of the subject, in the opinion of the investigator. * Has known symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable without evidence of progression by imaging for at least four weeks after definitive intervention and using no more than the equivalent of dexamethasone 2mg/d for the management of vasogenic edema, if necessary. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability. * Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy \[\</= 10 mg/d equivalent of prednisone\] for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with previous grade III/IV toxicity from immunotherapy that led to treatment discontinuation are excluded. * Has an active infection requiring systemic therapy. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial, in the opinion of the investigator. * Is pregnant or breastfeeding. * Has a known history of Human Immunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C. * Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate of CC-122 in Combination With Nivolumab | Up to 52 weeks | Objective Response Rate of CC-122 in combination with Nivolumab in both anti-PD1 therapy naive advanced melanoma as well as anti-PD1 therapy refractory melanoma (primary refractory or progressing after an initial response or stable disease) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience Treatment Related Adverse Events | Up to 52 weeks | All Adverse Events and Serious Adverse events will be collected and collated according to grade and frequency. This will include all events considered possibly, probably or definitely related to study therapy. |
| Tumor Response | Up to 52 weeks | Tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and and iRECIST (Response Evaluation Criteria in Solid Tumors in immunotherapy) guidelines v1.1. Results will be indicated as number of participants with evaluable tumor response. |
| Progression Free Survival | Up to 24 months | Progression free survival will be calculated from the start of study therapy till the first documentation of disease progression, death, or change of treatment. Subjects receiving ongoing therapy at the time of data analysis will be censored |
| Overall Survival | Up to 24 months | Overall survival will be calculated from the start of therapy till death from any cause. Subjects alive at the time of data analysis will be censored. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Anti-PD1 Naive Anti-PD1 naive participants will take CC-122 orally at 2mg daily for 5 consecutive days every 7 days, with intravenous nivolumab (240mg) in days 1 and 15 within a 28-day cycle.
CC-122: Oral CC-122 at 2 mg daily, 5 days out of 7 Nivolumab: 240 mg Nivolumab intravenously days 1 and 15 in each 28 day cycle | 11 |
| Cohort 2: Anti-PD1 Refractory Anti-PD1 refractory participants will take CC-122 orally at 2mg daily for 5 consecutive days every 7 days, with intravenous nivolumab (240mg) in days 1 and 15 within a 28-day cycle.
CC-122: Oral CC-122 at 2 mg daily, 5 days out of 7 Nivolumab: 240 mg Nivolumab intravenously days 1 and 15 in each 28 day cycle | 12 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Progression | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 2: Anti-PD1 Refractory | Total | Cohort 1: Anti-PD1 Naive |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 15 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 20 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 21 Participants | 10 Participants |
| Region of Enrollment United States | 12 participants | 23 participants | 11 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 9 Participants | 17 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 3 / 12 |
| other Total, other adverse events | 11 / 11 | 12 / 12 |
| serious Total, serious adverse events | 3 / 11 | 6 / 12 |
Outcome results
Primary
Objective Response Rate of CC-122 in Combination With Nivolumab
Objective Response Rate of CC-122 in combination with Nivolumab in both anti-PD1 therapy naive advanced melanoma as well as anti-PD1 therapy refractory melanoma (primary refractory or progressing after an initial response or stable disease)
Time frame: Up to 52 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Anti-PD1 Naive | Objective Response Rate of CC-122 in Combination With Nivolumab | .545 proportion of participants |
| Cohort 2: Anti-PD1 Refractory | Objective Response Rate of CC-122 in Combination With Nivolumab | 0 proportion of participants |
Secondary
Number of Participants Who Experience Treatment Related Adverse Events
All Adverse Events and Serious Adverse events will be collected and collated according to grade and frequency. This will include all events considered possibly, probably or definitely related to study therapy.
Time frame: Up to 52 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Anti-PD1 Naive | Number of Participants Who Experience Treatment Related Adverse Events | 11 participants |
| Cohort 2: Anti-PD1 Refractory | Number of Participants Who Experience Treatment Related Adverse Events | 12 participants |
Secondary
Overall Survival
Overall survival will be calculated from the start of therapy till death from any cause. Subjects alive at the time of data analysis will be censored.
Time frame: Up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Anti-PD1 Naive | Overall Survival | NA months |
| Cohort 2: Anti-PD1 Refractory | Overall Survival | 11.5 months |
Secondary
Progression Free Survival
Progression free survival will be calculated from the start of study therapy till the first documentation of disease progression, death, or change of treatment. Subjects receiving ongoing therapy at the time of data analysis will be censored
Time frame: Up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Anti-PD1 Naive | Progression Free Survival | NA months |
| Cohort 2: Anti-PD1 Refractory | Progression Free Survival | 2.7 months |
Secondary
Tumor Response
Tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and and iRECIST (Response Evaluation Criteria in Solid Tumors in immunotherapy) guidelines v1.1. Results will be indicated as number of participants with evaluable tumor response.
Time frame: Up to 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Anti-PD1 Naive | Tumor Response | 11 Participants |
| Cohort 2: Anti-PD1 Refractory | Tumor Response | 12 Participants |