CMP-001 in Combination With Nivolumab in Subjects With Advanced Melanoma

Melanoma Clinical Trial

Official title:

A Multicenter, Open-label, Phase 2 Study of Intratumoral CMP-001 in Combination With Intravenous Nivolumab in Subjects With Refractory Unresectable or Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04698187
• Other study ID #: CMP-001-010
• Status: Completed
• Phase: Phase 2
• Start date: March 11, 2021
• Est. completion date: February 5, 2024

Study information

• Verified date: February 2024
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

CMP-001-010 is a Phase 2 study of CMP-001 intratumoral (IT) and nivolumab intravenous (IV) administered to participants with refractory unresectable or metastatic melanoma. The primary objective of the study is to determine confirmed objective response with CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. The secondary objectives are to: - To evaluate the safety and tolerability of CMP-001 administered by intratumoral (IT) injection in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. - To evaluate the efficacy of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. - To assess the pharmacokinetic (PK) profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. - To assess and describe the immunogenicity of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma.

Description:

Former Sponsor Checkmate Pharmaceuticals

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: February 5, 2024
• Est. primary completion date: February 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Subjects enrolled in the study must meet all of the following inclusion criteria to be eligible.

1. Histopathologically-confirmed diagnosis of malignant melanoma that is metastatic or unresectable at Screening.

2. Known BRAF mutation status; if BRAF V600 mutation positive, must have had prior treatment with a local Health Authority approved BRAF inhibitor, with or without mitogen-activated protein kinase inhibitor. Patients with BRAF V600 mutations who refuse a BRAF inhibitor will not be eligible.

3. Refractory to PD-1 blockade either as monotherapy or in combination with other

therapies, as defined by the following criteria:

1. Received treatment with a Food and Drug Administration approved PD-1 blocking antibody for 12 weeks or longer.

2. Have PD (according to RECIST v1.1) within 12 weeks of the last dose of a PD-1 blocking antibody, either as monotherapy or in combination with other agents. Evidence of confirmed PD must be established by investigator assessment at least 4 weeks after the initial date of PD. The second assessment may serve as the Baseline for this study if completed within 30 days before to the start of study treatment. NOTE: in subjects with histologically confirmed recurrence on or after adjuvant PD-1 blocking antibody, confirmatory imaging is not required.

4. Measurable disease, as defined by RECIST v1.1 and all 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. Documented disease progression in any lesion that was previously radiated in order to serve as a target lesion.

5. Able to provide tissue from a core or excisional biopsy (fine needle aspirate is not sufficient). A fresh tissue biopsy (within 90 days before the start of study treatment) is preferred but an archival sample is acceptable if no intervening therapy was received. Note: For tissue sampling details, please refer to the laboratory manual.

6. Adequate organ function based on most recent laboratory values within 3 weeks before

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 times the upper limit of normal (ULN) with the following exception: patients with Gilbert Disease total serum bilirubin = 3 times ULN
• aspartate aminotransferase and alanine aminotransferase = 3 times the ULN

3. Lactate dehydrogenase = 2 times the 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 times 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 times ULN, unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants

7. Age = 18 years at time of consent.

8. Eastern Cooperative Oncology Group Performance Status of 0 to 1 at Screening.

9. Capable of understanding and complying with protocol requirements.

10. Women of childbearing potential must have negative serum pregnancy test before dosing at W1D1 and be willing to use an adequate method of contraception from the time of consent until at least 150 days after last dose of study treatment.

11. 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 radiation therapy (or other nonsystemic therapy) within 2 weeks before first dose of study treatment on W1D1. Patients should have recovered (ie, Grade =1 or at baseline) from radiation-related toxicities.

3. Treatment with complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before start of study treatment. Refer to Section 4.4. for prohibited therapies.

4. Received systemic pharmacologic doses of corticosteroids =10 mg/day prednisone within 30 days before 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 before enrollment.

2. Replacement doses, topical, ophthalmologic, and inhalational steroids are permitted.

3. Stress-dose corticosteroids will be required in subjects with adrenal insufficiency

5. History of immune-related AE that required permanent discontinuation of PD-1 blocking antibody.

6. Not fully recovered from AEs (to Grade 1 or less [per CTCAE v5.0], with the exception of persistent adverse events or sequelae, eg, vitiligo, alopecia, hypothyroidism, diabetes mellitus, and adrenal and/or pituitary insufficiency) due to prior treatment. NOTE: Subjects previously treated with a CTLA-4-blocking antibody, subjects receiving corticosteroids with daily doses > 5 mg and = 10 mg of prednisone equivalent for 2 weeks, and subjects with clinical symptoms and/or laboratory findings suggesting risk for adrenal insufficiency should undergo diagnostic tests for adrenal insufficiency via local laboratory.

7. Active pneumonitis or history of noninfectious pneumonitis that required steroids.

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, or implanted or continuous use of a pacemaker or defibrillator.

9. Known history of immunodeficiency.

10. Known additional malignancy that is progressing or required active treatment within the past 3 years. Exceptions include cancers that have undergone potentially curative therapy, eg, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, 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, and thyroid cancer (except anaplastic), in situ breast cancer, 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. Active infection requiring systemic therapy.

15. Known or suspected active infection with severe acute respiratory syndrome coronavirus 2 virus.

16. Known or suspected active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus (testing is not required unless suspected).

17. Received a live virus/attenuated vaccination within 30 days before 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 before 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 study.

21. Participation in another clinical study of an investigational anticancer therapy or device within 30 days before first dose of study treatment on W1D1. 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. Received previous CMP-001 treatment.

25. Pregnant or breastfeeding 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 last dose of study treatment for women.

Related Conditions & MeSH terms

• Advanced Melanoma
• Melanoma
• Metastatic Melanoma
• Unresectable Melanoma

Intervention

Drug:
• CMP-001
Subjects will receive CMP-001 10 mg IT weekly for 7 doses after which CMP-001 will be administered every 3 weeks (Q3W).
• Nivolumab
Nivolumab 360 mg IV is administered Q3W.

Locations

Country	Name	City	State
United States	University Cancer & Blood Center	Athens	Georgia
United States	Emory University Winship Cancer Institute	Atlanta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	Sammons Cancer Center	Dallas	Texas
United States	University of Colorado- Denver	Denver	Colorado
United States	City of Hope National Medical Center, Robert Kang, MD	Duarte	California
United States	Duke University Cancer Institute	Durham	North Carolina
United States	Hartford Healthcare	Hartford	Connecticut
United States	University of Iowa	Iowa City	Iowa
United States	GenesisCare USA	Jacksonville	Florida
United States	UCLA Hematology-Oncology	Los Angeles	California
United States	University of Louisville Health Care	Louisville	Kentucky
United States	Columbia University Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Orlando Health	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of Utah- Huntsman Cancer Institute	Salt Lake City	Utah
United States	California Cancer Associates for Research & Excellence, Inc.	San Marcos	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine confirmed objective response (ORR) with CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma	Defined as proportion of subjects with confirmed complete or partial response based on RECIST v1.1, per blinded independent central review (BICR).	From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Secondary	Evaluate the safety and tolerability of CMP-001 administered by IT injection in combination with nivolumab	Based on adverse events, serious AEs, AEs leading to discontinuation or death, and severity of AEs per NCI CTCAE v5.0 in subjects with refractory unresectable or metastatic melanoma.	From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Secondary	Duration of response (DOR)	Time from the date of first documented response (CR or PR) to the date of documented progressive disease (PD), based on RECIST v1.1 by BICR.	From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Secondary	Treatment response in non-injected target lesions	Treatment response in non-injected target lesions based on RECIST v1.1 by BICR.	From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Secondary	Progression-free survival (PFS)	The time from date of first dose of study treatment to date of documented PD based on RECIST v1.1 by BICR or death, whichever occurs first.	From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)
Secondary	Overall survival (OS)	The time from date of first dose of study treatment to date of death.	From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)
Secondary	Immune objective response rate (iORR)	The proportion of subjects with a best overall response (BOR) of immune complete response (iCR) or immune partial response (iPR) based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IA.	From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)
Secondary	Immune duration of response (iDOR)	The time from the date of the first immune response (iCR or iPR) to the date of immune confirmed progressive disease (iCPD) by IA.	From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)
Secondary	Immune progression-free survival (iPFS)	The time from date of first dose of study drug to date of iCPD by IA or death, whichever occurs first.	From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)
Secondary	Assess the PK profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma for maximum observed serum concentration	Assess the PK profile for maximum observed serum concentration.	From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Secondary	Assess the PK profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma for area under the serum concentration-time curve from time zero to the last quantifiable time point	Assess the PK profile for area under the serum concentration-time curve from time zero to the last quantifiable time point.	From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Secondary	Assess the PK profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma for area under the serum concentration-time curve from time zero extrapolated to infinity	Assess the PK profile for area under the serum concentration-time curve from time zero extrapolated to infinity.	From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Secondary	Assess the PK profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma for a terminal elimination half-life	Assess the PK profile for terminal elimination half-life.	From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Secondary	Assess and describe the immunogenicity of CMP-001 in combination with nivolumab by detecting development of anti-Qbeta antibodies in subjects with refractory unresectable or metastatic melanoma	Detecting and describing development of anti-Qbeta antibodies in subjects with refractory unresectable or metastatic melanoma.	From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)