Melanoma, Advanced Melanoma, Metastatic Melanoma, Unresectable Melanoma
Conditions
Keywords
vidutolimod
Brief summary
CMP-001-011 is a Phase 2/3 study of CMP-001 intratumoral (IT) and nivolumab intravenous (IV) compared to nivolumab monotherapy administered to participants with unresectable or metastatic melanoma. The study is divided into two phases: Phase 2 and Phase 3. The primary objective of Phase 2 of the study is to determine confirmed objective response rate (ORR) for treatment with first-line CMP-001 in combination with nivolumab versus nivolumab monotherapy in subjects with unresectable or metastatic melanoma. The secondary objective of Phase 2 of the study is to evaluate the safety and tolerability of first-line CMP-001 in combination with nivolumab versus nivolumab monotherapy in subjects with unresectable or metastatic melanoma. The primary objective of Phase 3 of the study is to evaluate progression-free survival (PFS) for subjects receiving first-line CMP-001 in combination with nivolumab versus nivolumab monotherapy for unresectable or metastatic melanoma. The secondary objectives of Phase 3 are to: * To evaluate the safety and tolerability of first-line CMP-001 in combination with nivolumab versus nivolumab monotherapy in subjects with unresectable or metastatic melanoma. * To evaluate the efficacy of first-line CMP-001 in combination with nivolumab versus nivolumab monotherapy in subjects with unresectable or metastatic melanoma.
Detailed description
Former Sponsor Checkmate Pharmaceuticals
Interventions
DRUGCMP-001
Subjects will receive CMP-001 10 mg IT weekly for 7 doses after which CMP-001 will be administered every 3 weeks (Q3W).
DRUGNivolumab
Nivolumab 360 mg IV is administered Q3W.
Sponsors
Bristol-Myers Squibb
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects enrolled in the study must meet all of the following inclusion criteria to be eligible: 1. Histologically or cytologically confirmed unresectable Stage III or Stage IV melanoma per AJCC Cancer Staging Manual Eighth Edition. 2. Measurable disease, as defined by RECIST v1.1 and both of the following: 1. At least 1 accessible lesion amenable to repeated IT injection 2. One or more measurable lesions at least 1 cm in diameter that are not intended for CMP-001 injection and can be followed as target lesions per RECIST v1.1 3. Able to provide tissue from a core or excisional biopsy (fine needle aspirate is not sufficient). A newly obtained biopsy (within 90 days before the first dose of study treatment) is preferred, but an archival sample is acceptable if no intervening therapy for melanoma/cancer was received. Note: for tissue sampling details, please refer to the Laboratory Manual. 4. Adequate organ function based on most recent laboratory values within 3 weeks before the first dose of study treatment on Week 1 Day 1 (W1D1): 1. Bone marrow function: * neutrophil count ≥1500/mm3 * platelet count ≥ 100 000/mm3 * hemoglobin concentration ≥9 g/dL * white blood cells ≥2000/mm3 2. Liver function: * total bilirubin ≤1.5 × the upper limit of normal (ULN) with the following exception: subjects with Gilbert Disease total serum bilirubin ≤3 × ULN * aspartate aminotransferase and alanine aminotransferase ≤3 ×ULN 3. Lactate dehydrogenase ≤2 × ULN 4. Renal function: estimated (Cockcroft-Gault) or measured creatinine clearance ≥30 mL/min 5. Coagulation * International normalized ratio or prothrombin time (PT) ≤ 1.5 × ULN, unless subject is receiving anticoagulant therapy, as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants * Activated partial thromboplastin time or PTT ≤1.5 × ULN, unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants 5. Eastern Cooperative Oncology Group Performance Status of 0 to 1 at Screening. 6. Age ≥18 years at time of consent. 7. Capable of understanding and complying with protocol requirements. 8. Women of childbearing potential must have negative serum pregnancy test prior to dosing at W1D1 and be willing to use an adequate method of contraception from the time of consent until at least 150 days after the last dose of study treatment. 9. Male subjects must be surgically sterile or must agree to use adequate method of contraception from the time of consent until at least 210 days after the last dose of study treatment. 10. Able and willing to provide written informed consent and to follow study instructions. Subjects unable to provide written informed consent on their own behalf will not be eligible for the study.
Exclusion criteria
Subjects presenting with any of the following will not qualify for entry into the study: 1. Uveal, acral, or mucosal melanoma. 2. Received prior systemic treatment for melanoma in the unresectable or metastatic setting. Prior adjuvant therapy is acceptable if the treatment course (of approximately 1 year duration) was completed and there was no recurrence within 6 months of the last dose of adjuvant treatment. 3. Received prior therapy with CMP-001. 4. Requires systemic pharmacologic doses of corticosteroids greater than the equivalent of 10 mg/day prednisone within 30 days before the first dose of study treatment on W1D1. 1. Subjects who are currently receiving steroids at a prednisone-equivalent dose of ≤10 mg/day do not need to discontinue steroids prior to enrollment. 2. Replacement doses, topical, ophthalmologic, and inhalational steroids are permitted. 5. History of CTCAE v5.0 Grade 4 immune-related AE due to adjuvant CTLA-4 or PD-1 blocking antibody. 6. Not fully recovered from adverse events (to Grade 1 or less \[per CTCAE v5.0\], with the exception of persistent alopecia, adrenal insufficiency, and hypothyroidism) due to prior treatment. 7. Active pneumonitis, history of pneumonitis that required steroids, or history of interstitial lung disease. 8. Severe uncontrolled cardiac disease within 6 months of Screening, including but not limited to poorly controlled hypertension, unstable angina, myocardial infarction, congestive heart failure (New York Heart Association Class II or greater), pericarditis within the previous 6 months, cerebrovascular accident, and implanted or continuous use of a pacemaker or defibrillator. 9. Known history of immunodeficiency. 10. Known additional malignancy that has progressed or required active treatment within the past 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, curatively treated localized prostate cancer with prostate-specific antigen level below 4.0 ng/mL, in situ cervical cancer on biopsy or a squamous intraepithelial lesion on Papanicolaou smear, thyroid cancer (except anaplastic), and adjuvant hormonal therapy for breast cancer \>3 years from curative-intent surgical resection. 11. Active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment. 12. Untreated, symptomatic, or enlarging central nervous system metastases or carcinomatous meningitis (including leptomeningeal metastases from solid tumors). 13. Prior allogenic tissue/solid organ transplant. 14. Known or suspected active infection with severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2). 15. Active infection requiring systemic therapy. 16. Known or suspected infection with HIV, hepatitis B virus, or hepatitis C virus; testing is not required unless suspected. 17. Received a live/attenuated virus vaccination within 30 days prior to the first dose of study treatment on W1D1. 18. Received blood products (including platelets or red blood cells) or colony stimulating factors (including granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor, or recombinant erythropoietin) within 30 days prior to the start of Screening. 19. History of allergy or hypersensitivity to nivolumab and/or any of its excipients. 20. Any concurrent uncontrolled illness, including mental illness or substance abuse, which in the opinion of the Investigator, would make the subject unable to cooperate or participate in the trial. 21. Participation in another clinical study of an investigational anticancer therapy or device within 30 days before the first dose of study treatment on W1D1. Note: Participation in the follow-up phase (receiving no study treatment) of a prior study is allowed. 22. Requires prohibited treatment (ie, non-protocol specified anticancer pharmacotherapy, surgery, or radiotherapy) for treatment of malignant tumor. 23. Has a life expectancy of less than 3 months and/or has rapidly progressing disease (eg, tumor bleeding, uncontrolled tumor pain) in the opinion of the treating Investigator. 24. Pregnant or breast-feeding or expecting to conceive or donate eggs within the projected duration of the study, from the time of consent until at least 150 days after the last dose of study treatment for women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) | Up to approximately 39 months | ORR, defined as the percentage of participants who have confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST vl.l) as assessed by Blinded Independent Central Review (BICR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Up to approximately 28 months (122 weeks) | Number of participants per NCI CTCAE version 5.0 Adverse Event Grade reported: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2 Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living; Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limited self-care activities of daily living; Grade 4 Life-threatening consequences: urgent intervention indicated; Grade 5 Death related to adverse event. |
| Time to Response (TTR) by BICR | Up to approximately 39 months | TTR, defined as the time from the date of randomization to the first time when criteria are first met for complete response (CR) or partial response (PR), whichever occurred first, per RECIST vl.1 by BICR. |
| Time to Response (TTR) by Investigator | Up to approximately 39 months | TTR, defined as the time from the date of randomization to the first time when criteria are first met for CR or PR, whichever occurred first, per RECIST vl.1 by Investigator. |
| Duration of Response (DOR) by BICR | Up to approximately 39 months | DOR, defined as time from the date of first documented response (CR or PR) to the date of documented progressive disease (PD), based on RECIST vl.1 by BICR or death, whichever occurred first. |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any Serious TEAE, and Any TEAE Leading to Discontinuation or Death | Up to approximately 28 months (122 weeks) | Number of participants with any treatment-emergent adverse event (TEAE), any serious TEAE, and any TEAE leading to discontinuation or death reported. |
| Confirmed ORR in Non-injected Target Lesions by Investigator | Up to approximately 39 months | Confirmed ORR, defined as the percentage of participants in the analysis set who had confirmed BOR of CR or PR based on RECIST vl.1 as assessed by Investigator. |
| Progression-free Survival (PFS) by BICR | Up to approximately 39 months | PFS, defined as the time from the date of randomization to date of documented PD based on RECIST vl.1 by BICR or death, whichever occurred first. |
| Progression-free Survival (PFS) by Investigator | Up to approximately 39 months | PFS, defined as the time from the date of randomization to date of documented PD based on RECIST vl.1 by Investigator or death, whichever occurred first. |
| Overall Survival (OS) by Investigator | Up to approximately 40 months (174 weeks) | OS, defined as the time from the date of randomization to the date of death from any cause. |
| Duration of Response (DOR) by Investigator | Up to approximately 39 months | DOR, defined as time from the date of first documented response (CR or PR) to the date of documented progressive disease (PD), based on RECIST vl.1 by Investigator or death, whichever occurred first. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab Monotherapy All participants received nivolumab monotherapy IV according to the treatment schedule. | 11 |
| CMP-001 and Nivolumab All participants received CMP-001 IT and nivolumab IV according to the treatment schedule. | 9 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 5 |
| Overall Study | Sponsor Decision | 9 | 4 |
Baseline characteristics
| Characteristic | CMP-001 and Nivolumab | Total | Nivolumab Monotherapy |
|---|---|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 7.14 | 69.3 years STANDARD_DEVIATION 9.04 | 71.3 years STANDARD_DEVIATION 10.22 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 19 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 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 | 0 Participants | 0 Participants | 0 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 | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 18 Participants | 10 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 13 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 11 | 5 / 9 |
| other Total, other adverse events | 11 / 11 | 9 / 9 |
| serious Total, serious adverse events | 5 / 11 | 2 / 9 |
Outcome results
Primary
Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR)
ORR, defined as the percentage of participants who have confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST vl.l) as assessed by Blinded Independent Central Review (BICR)
Time frame: Up to approximately 39 months
Population: ITT Analysis Set (includes all participants who were randomized)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab Monotherapy | Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) | 73 Percentage of participants |
| CMP-001 and Nivolumab | Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) | 44 Percentage of participants |
Secondary
Confirmed ORR in Non-injected Target Lesions by Investigator
Confirmed ORR, defined as the percentage of participants in the analysis set who had confirmed BOR of CR or PR based on RECIST vl.1 as assessed by Investigator.
Time frame: Up to approximately 39 months
Population: Number of participants analyzed included only participants in the ITT Analysis Set who had at least one non-injected target lesion, as assessed by Investigator, in the CMP-001 and Nivolumab reporting group, as prespecified by the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab Monotherapy | Confirmed ORR in Non-injected Target Lesions by Investigator | 56 Percentage of participants |
Secondary
Duration of Response (DOR) by BICR
DOR, defined as time from the date of first documented response (CR or PR) to the date of documented progressive disease (PD), based on RECIST vl.1 by BICR or death, whichever occurred first.
Time frame: Up to approximately 39 months
Population: Number of participants analyzed for DOR included only participants in the ITT Analysis Set who had a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) by BICR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Monotherapy | Duration of Response (DOR) by BICR | NA Months |
| CMP-001 and Nivolumab | Duration of Response (DOR) by BICR | NA Months |
Secondary
Duration of Response (DOR) by Investigator
DOR, defined as time from the date of first documented response (CR or PR) to the date of documented progressive disease (PD), based on RECIST vl.1 by Investigator or death, whichever occurred first.
Time frame: Up to approximately 39 months
Population: Number of participants analyzed for DOR included only participants in the ITT Analysis Set who had a confirmed BOR of CR or PR by Investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Monotherapy | Duration of Response (DOR) by Investigator | NA Months |
| CMP-001 and Nivolumab | Duration of Response (DOR) by Investigator | NA Months |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any Serious TEAE, and Any TEAE Leading to Discontinuation or Death
Number of participants with any treatment-emergent adverse event (TEAE), any serious TEAE, and any TEAE leading to discontinuation or death reported.
Time frame: Up to approximately 28 months (122 weeks)
Population: Safety Analysis Set (all participants who received at least 1 dose of study treatment)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nivolumab Monotherapy | Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any Serious TEAE, and Any TEAE Leading to Discontinuation or Death | Any TEAE | 11 Participants |
| Nivolumab Monotherapy | Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any Serious TEAE, and Any TEAE Leading to Discontinuation or Death | Any Serious TEAE | 5 Participants |
| Nivolumab Monotherapy | Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any Serious TEAE, and Any TEAE Leading to Discontinuation or Death | Any TEAE leading to death | 0 Participants |
| CMP-001 and Nivolumab | Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any Serious TEAE, and Any TEAE Leading to Discontinuation or Death | Any TEAE | 9 Participants |
| CMP-001 and Nivolumab | Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any Serious TEAE, and Any TEAE Leading to Discontinuation or Death | Any Serious TEAE | 2 Participants |
| CMP-001 and Nivolumab | Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any Serious TEAE, and Any TEAE Leading to Discontinuation or Death | Any TEAE leading to death | 0 Participants |
Secondary
Overall Survival (OS) by Investigator
OS, defined as the time from the date of randomization to the date of death from any cause.
Time frame: Up to approximately 40 months (174 weeks)
Population: ITT Analysis Set (includes all participants who were randomized)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Monotherapy | Overall Survival (OS) by Investigator | NA Months |
| CMP-001 and Nivolumab | Overall Survival (OS) by Investigator | 20.04 Months |
Secondary
Progression-free Survival (PFS) by BICR
PFS, defined as the time from the date of randomization to date of documented PD based on RECIST vl.1 by BICR or death, whichever occurred first.
Time frame: Up to approximately 39 months
Population: ITT Analysis Set (includes all participants who were randomized)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Monotherapy | Progression-free Survival (PFS) by BICR | NA Months |
| CMP-001 and Nivolumab | Progression-free Survival (PFS) by BICR | 14.85 Months |
Secondary
Progression-free Survival (PFS) by Investigator
PFS, defined as the time from the date of randomization to date of documented PD based on RECIST vl.1 by Investigator or death, whichever occurred first.
Time frame: Up to approximately 39 months
Population: ITT Analysis Set (includes all participants who were randomized)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Monotherapy | Progression-free Survival (PFS) by Investigator | NA Months |
| CMP-001 and Nivolumab | Progression-free Survival (PFS) by Investigator | 10.25 Months |
Secondary
Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Number of participants per NCI CTCAE version 5.0 Adverse Event Grade reported: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2 Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living; Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limited self-care activities of daily living; Grade 4 Life-threatening consequences: urgent intervention indicated; Grade 5 Death related to adverse event.
Time frame: Up to approximately 28 months (122 weeks)
Population: Safety Analysis Set (all participants who received at least 1 dose of study treatment)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nivolumab Monotherapy | Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Grade 2 Moderate | 1 Participants |
| Nivolumab Monotherapy | Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Grade 4 Life-threatening | 0 Participants |
| Nivolumab Monotherapy | Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Grade 3 Severe | 8 Participants |
| Nivolumab Monotherapy | Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Grade 5 Death | 0 Participants |
| Nivolumab Monotherapy | Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Grade 1 Mild | 2 Participants |
| CMP-001 and Nivolumab | Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Grade 5 Death | 0 Participants |
| CMP-001 and Nivolumab | Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Grade 1 Mild | 0 Participants |
| CMP-001 and Nivolumab | Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Grade 2 Moderate | 6 Participants |
| CMP-001 and Nivolumab | Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Grade 3 Severe | 3 Participants |
| CMP-001 and Nivolumab | Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Grade 4 Life-threatening | 0 Participants |
Secondary
Time to Response (TTR) by BICR
TTR, defined as the time from the date of randomization to the first time when criteria are first met for complete response (CR) or partial response (PR), whichever occurred first, per RECIST vl.1 by BICR.
Time frame: Up to approximately 39 months
Population: Number of participants analyzed for TTR included only participants in the ITT Analysis Set who had a confirmed best overall response (BOR) of CR or PR by BICR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Monotherapy | Time to Response (TTR) by BICR | 2.14 Months |
| CMP-001 and Nivolumab | Time to Response (TTR) by BICR | 2.27 Months |
Secondary
Time to Response (TTR) by Investigator
TTR, defined as the time from the date of randomization to the first time when criteria are first met for CR or PR, whichever occurred first, per RECIST vl.1 by Investigator.
Time frame: Up to approximately 39 months
Population: Number of participants analyzed for TTR included only participants in the ITT Analysis Set who had a confirmed BOR of CR or PR by Investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Monotherapy | Time to Response (TTR) by Investigator | 2.14 Months |
| CMP-001 and Nivolumab | Time to Response (TTR) by Investigator | 3.45 Months |