A Randomized Study of the Efficacy and Safety of Neoadjuvant Therapy With BCD-217 (Nurulimab + Prolgolimab) Versus Standard Adjuvant Therapy With Pembrolizumab in Patients With Resectable Stage III Skin Melanoma.
Overview
- Phase
- Phase 3
- Intervention
- BCD-217
- Conditions
- Melanoma Stage III
- Sponsor
- Biocad
- Enrollment
- 411
- Locations
- 36
- Primary Endpoint
- event free survival (EFS)
- Status
- Active, not recruiting
- Last Updated
- 9 months ago
Overview
Brief Summary
This study is an open-label, randomized, comparative phase III study, which will include subjects with resectable stage III skin melanoma (up to 3 resectable transient metastases are acceptable).
Detailed Description
In both study groups, adjuvant therapy is possible until melanoma progresses to unresectable stage III-IV, unacceptable toxicity, withdrawal of ICF or the end of the therapy period (12 months). In case of postoperative relapse of the disease, at the decision of the investigator and if the lesion is resectable, radical surgical treatment can be carried out (R0 - resection) in accordance with current clinical guidelines without withdrawing the patient from the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent and the subject's ability to comply with the requirements of the clinical study protocol;
- •Age ≥ 18 years at the time of signing the informed consent form;
- •Histologically or cytologically confirmed (documented results of relevant studies are available) resectable stage IIIB/C/D skin melanoma;
- •At least one clinically detectable lymph node accessible for biopsy and not more than three resectable in-transit metastases .
- •Clinically detectable lymph nodes include:
- •Palpable lymph nodes with pathologically confirmed melanoma
- •Non-palpable but enlarged (≥15 mm in smallest diameter, RECIST 1.1) lymph nodes with pathologically confirmed melanoma
- •Subject's consent to a biopsy;
- •Consent to the evaluation of the PD-L1 status and BRAF V600 mutation status ;
- •ECOG score 0-1;
Exclusion Criteria
- •Ocular melanoma;
- •Mucosal melanoma;
- •Distant metastases;
- •Impossibility of radical resection of the tumor, metastasis and/or involved lymph nodes;
- •Presence of only in-transit transit/satellite metastases without confirmed involvement of lymph nodes;
- •Prior therapy with checkpoint inhibitors (e.g. anti-CTLA-4 and/or anti-PD-1/PD-L1/PD-L2 products);
- •Prior therapy with BRAF and MEK protein kinase inhibitors;
- •Prior radiation therapy;
- •Inability to determine BRAF status;
- •Subjects with severe comorbidities, with life-threatening acute complications of the underlying disease at the time of signing the informed consent form;
Arms & Interventions
Subjects with pCR and pnCR (Group 1A)
Subjects will receive 2 cycles of BCD-217 neoadjuvant therapy, followed by index lymph node removal. Subjects with pathological complete (pCR) and near complete response (pnCR) (Group 1A): excision of the primary lesion (if not previously performed) without regional lymphadenectomy, followed by up to 12 months of anti-PD1 agent in the adjuvant setting.
Intervention: BCD-217
Subjects with pCR and pnCR (Group 1A)
Subjects will receive 2 cycles of BCD-217 neoadjuvant therapy, followed by index lymph node removal. Subjects with pathological complete (pCR) and near complete response (pnCR) (Group 1A): excision of the primary lesion (if not previously performed) without regional lymphadenectomy, followed by up to 12 months of anti-PD1 agent in the adjuvant setting.
Intervention: anti-PD1
Subjects with pCR and pnCR (Group 1A)
Subjects will receive 2 cycles of BCD-217 neoadjuvant therapy, followed by index lymph node removal. Subjects with pathological complete (pCR) and near complete response (pnCR) (Group 1A): excision of the primary lesion (if not previously performed) without regional lymphadenectomy, followed by up to 12 months of anti-PD1 agent in the adjuvant setting.
Intervention: Excision of the primary lesion
Subjects with a pPR or pNR to neoadjuvant therapy (Group 1B)
Subjects will receive 2 cycles of BCD-217 neoadjuvant therapy, followed by index lymph node removal. Subjects with a pathological partial response (pPR) or non-responders (pNR) to neoadjuvant therapy (Group 1B): excision of the primary lesion (if not performed earlier), regional lymphadenectomy, then up to 12 months of adjuvant therapy with anti-PD1 agent.
Intervention: BCD-217
Subjects with a pPR or pNR to neoadjuvant therapy (Group 1B)
Subjects will receive 2 cycles of BCD-217 neoadjuvant therapy, followed by index lymph node removal. Subjects with a pathological partial response (pPR) or non-responders (pNR) to neoadjuvant therapy (Group 1B): excision of the primary lesion (if not performed earlier), regional lymphadenectomy, then up to 12 months of adjuvant therapy with anti-PD1 agent.
Intervention: anti-PD1
Subjects with a pPR or pNR to neoadjuvant therapy (Group 1B)
Subjects will receive 2 cycles of BCD-217 neoadjuvant therapy, followed by index lymph node removal. Subjects with a pathological partial response (pPR) or non-responders (pNR) to neoadjuvant therapy (Group 1B): excision of the primary lesion (if not performed earlier), regional lymphadenectomy, then up to 12 months of adjuvant therapy with anti-PD1 agent.
Intervention: Excision of the primary lesion
Subjects with a pPR or pNR to neoadjuvant therapy (Group 1B)
Subjects will receive 2 cycles of BCD-217 neoadjuvant therapy, followed by index lymph node removal. Subjects with a pathological partial response (pPR) or non-responders (pNR) to neoadjuvant therapy (Group 1B): excision of the primary lesion (if not performed earlier), regional lymphadenectomy, then up to 12 months of adjuvant therapy with anti-PD1 agent.
Intervention: Regional lymphadenectomy
Control Group (Group 2)
Subjects start treatment with excision of the primary lesion (if not previously performed), regional lymphadenectomy followed by adjuvant therapy with anti-PD1 agent (up to 12 months). This approach is considered the standard therapy for patients in the target population.
Intervention: Excision of the primary lesion
Control Group (Group 2)
Subjects start treatment with excision of the primary lesion (if not previously performed), regional lymphadenectomy followed by adjuvant therapy with anti-PD1 agent (up to 12 months). This approach is considered the standard therapy for patients in the target population.
Intervention: Regional lymphadenectomy
Outcomes
Primary Outcomes
event free survival (EFS)
Time Frame: 24 months
Secondary Outcomes
- The proportion of subjects with immune-related adverse events of any severity(24 months)
- distant metastases-free survival (DMFS)(24 months)
- pathologic response rate (pRR)(24 months)
- The proportion of subjects with severe immune-related adverse events (grade 3 or higher according to CTCAE v.5.0)(24 months)
- The proportion of subjects with treatment-related adverse events;(24 months)
- overall survival (OS)(24 months)
- The proportion of subjects with SAEs(24 months)
- The proportion of subjects experiencing any grade 3 or higher adverse events(24 months)
- The proportion of subjects requiring treatment discontinuation due to AEs(24 months)
- The proportion of BAb and NAb positive subjects(24 months)