International Trial of the Efficacy and Safety of BCD-100 in Patients With Melanoma (MIRACULUM)

• ClinicalTrials.gov Identifier: NCT03269565
• Recruitment Status: Active, not recruiting
• First Posted: September 1, 2017
• Last Update Posted: September 18, 2020
• Sponsor: Biocad
• Information provided by (Responsible Party): Biocad

Tracking Information

• First Submitted Date: August 30, 2017
• First Posted Date: September 1, 2017
• Last Update Posted Date: September 18, 2020
• Actual Study Start Date: August 31, 2017
• Actual Primary Completion Date: August 29, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 31, 2017)

Overall response rate [ Time Frame: 1 year ]

Overall response rate (partial response+complete response rates) assessed according to irRECIST in an mITT population during BCD-100 therapy

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 31, 2017)

• One-year progression-free survival rate ; [ Time Frame: 1 year ]
  One-year progression-free survival rate during BCD-100 therapy;
• Percentage of patients with severe immune-related AEs [ Time Frame: 1 year ]
  Percentage of patients with severe immune-related AEs (CTCAE 4.03 Grade 3 or greater);

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: International Trial of the Efficacy and Safety of BCD-100 in Patients With Melanoma
• Official Title: An International Multicenter Open-label Randomized Trial of the Efficacy, Pharmacokinetics, Safety, and Immunogenicity of BCD-100 (JSC BIOCAD, Russia) as Monotherapy in Patients With Unresectable/Metastatic Melanoma.
• Brief Summary: An International Multicenter Open-label Randomized Trial of the Efficacy, Pharmacokinetics, Safety, and Immunogenicity of BCD-100 (JSC BIOCAD, Russia) as Monotherapy in Patients with Unresectable/Metastatic Melanoma.

Detailed Description

This trial has been designed as an international multicenter open-label Phase II trial.

The trial aims to investigate the efficacy, pharmacokinetics, safety, and immunogenicity of two dosage regimens of BCD-100 (JSC BIOCAD, Russia) as monotherapy in patients with unresectable/metastatic melanoma.

According to the design, the trial will include two arms of patients. Each of the trial arms will receive repeated doses of the test drug as monotherapy; BCD-100 will be administered using one of the following dosage regimens established in a Phase I trial:

• Monotherapy, BCD-100 1 mg/kg Q2W (IV infusion over 60 minutes; if a 60-minute infusion is tolerated well, all following doses can be administered over 30 minutes);
• Monotherapy, BCD-100 3 mg/kg Q3W (IV infusion over 60 minutes; if a 60-minute infusion is tolerated well, all following doses can be administered over 30 minutes).

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Melanoma

Intervention

Biological: BCD-100

Anti-PD-1 monoclonal antibody

Study Arms

• Experimental: Arm 1
  BCD-100 1 mg/kg Q2W;
  Intervention: Biological: BCD-100
• Experimental: Arm 2
  BCD-100 3 mg/kg Q3W.
  Intervention: Biological: BCD-100

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 31, 2017): 126
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2021
• Actual Primary Completion Date: August 29, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Signed Informed Consent Form and the subject's ability to follow the Protocol requirements;
2. Age: 18 years and older at the signing of the informed consent;
3. Histologically verified (documented) unresectable/metastatic melanoma;
4. Newly diagnosed advanced/metastatic melanoma or progressive disease during (or after) systemic chemotherapy ;
5. Available tissue blocks for histological examination or patient's agreement to give biopsy specimens for PD-L1 expression status ;
6. ECOG performance status of 0 or 1;
7. LDH less than or equal to 2×upper limit of normal;
8. At least one RESICT 1.1-defined measurable target lesion confirmed by an independent review;
9. All prior treatment-related toxicities/surgery-related adverse events must be less than or equal to Grade 2 according to CTCAE 4.03, except for chronic/permanent damage caused by an AE that does not affect the safety profile of the investigational therapy (e.g., alopecia);
10. Adequate organ system function ;
11. Life expectancy of at least 12 weeks from the screening.
12. Patients with reproductive potential must agree to practice acceptable methods of birth control throughout the entire trial period, starting from signing the informed consent and up to 12 weeks after the last dose of BCD-100.

Exclusion Criteria:

1. Evidence of severe or concomitant diseases/life-threatening complications of the main condition (e.g., massive pleural, pericardial, or peritoneal effusion that requires medical intervention , pulmonary lymphangitis) at the signing of the informed consent;
2. Subjects with progressive/symptomatic brain metastases (e.g., brain edema, spinal cord compression) or brain metastases that need therapy with corticosteroids and/or anticonvulsants ;

3. Any concomitant disease observed at the screening that increases the risk of adverse events during the investigational therapy:

   • Grade III-IV stable angina, unstable angina, or a history of myocardial infarction within 6 months prior to signing the informed consent;
   • Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system;
   • Severe, resistant hypertension;
   • History of atopic asthma, angioedema;
   • Moderate to severe respiratory failure, Grade 3 to 4 chronic obstructive pulmonary disease;
   • Any other concomitant condition (e.g., metabolism, blood, hepatic, renal, pulmonary, neurological, endocrine, cardiac, infectious, or gastrointestinal disorder) that constitutes an unacceptable risk to the patient's health during the investigational therapy;
4. Systemic autoimmune diseases (including but not limited to SLE, Crohn's disease, ulcerative colitis, systemic scleroderma, inflammatory myopathy, mixed connective tissue disease, overlap syndrome, etc.) ;
5. Endocrine disorders that cannot be adequately controlled by hormone replacement therapy without any dose modification within 28 days prior to the start of the investigational therapy;
6. Patients who need therapy with corticosteroids or other immunosuppressants;

7. Blood disorders :

   • Neutrophils <1.5×109/L;
   • Platelets <100×109/L;
   • Hb <90 g/L;
8. Impaired renal function: creatinine ≥1.5×ULN;

9. Impaired liver function :

   • Bilirubin ≥1.5×ULN (≤50 μmol/L for patients with Gilbert's syndrome);
   • AST/ALT ≥2.5×ULN (5×ULN for patients with liver metastases);
   • ALP ≥5×ULN;
10. LDH >2×ULN;
11. Anti-cancer therapy (surgery, chemotherapy) within 28 days prior to the first dose of the investigational product; radiotherapy within 14 days prior to the first dose of the investigational product;
12. Prior treatment with anti-CTLA4 and/or anti-PD-1/PD-L1/PD-L2 agents;
13. Prior targeted therapy ;
14. Patients who have received more than two lines of systemic chemotherapy for unresectable or metastatic melanoma;
15. Concomitant cancer (except for cervical carcinoma in situ after radical surgery or basal cell/squamous cell carcinoma after radical surgery);
16. Any condition that prevents a patient from following the Protocol procedures (dementia, neurological or mental disorders, drug/alcohol abuse, etc.) ;
17. Simultaneous participation in other clinical trials , participation in other clinical trials within 30 days prior to the first dose of the investigational product;
18. Acute infection or the acute phase of chronic infection within 28 days prior the first dose of the investigational product;
19. Active HBV/HCV/HIV infection, active syphilis ;
20. Patients unable to receive an IV infusion of BCD-100;
21. Patients unable to receive an IV contrast agent;
22. Hypersensitivity to any of the components of BCD-100;
23. History of hypersensitivity to any therapeutic monoclonal antibody;
24. Pregnant or lactating female.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT03269565
• Other Study ID Numbers: BCD-100-2
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Biocad
• Study Sponsor: Biocad
• Collaborators: Not Provided

Investigators

• Study Director: Yulia N Linkova, MD, PhD; Director of Clinical Development Department, BIOCAD

• PRS Account: Biocad
• Verification Date: September 2020