Study to evaluate the efficacy and safety of novel spartalizumab combinations in patients with previously treated unresectable or metastatic melanoma

Phase 1

• Conditions: nresectable or metastatic melanoma; MedDRA version: 20.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-000610-38-IT
• Lead Sponsor: OVARTIS PHARMA AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Study Completion: 2022-12-30
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 196

Inclusion Criteria

Key inclusion criteria for Arm 1,2,3,4:
•Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma using AJCC edition 8
•Previously treated for unresectable or metastatic melanoma:
•Subjects with V600BRAF wild-type disease must have received prior systemic therapy for unresectable or metastatic melanoma with anti-PD-1/PD-L1. Additionally, subjects may have received anti-CTLA-4 as a single agent or in combination with anti- PD-1/PD-L1, irrespective of the sequence. No additional systemic treatment is allowed for advanced or metastatic melanoma. A maximum of two prior lines of systemic therapies for unresectable or metastatic melanoma are allowed. The last dose of prior therapy (anti-PD-1, anti-PD-L1 or anti-CTLA-4) must have been received more than four weeks before randomization.
•Subjects with V600BRAF mutant disease must have received prior systemictherapy for unresectable or metastatic melanoma with anti-PD-1/PD-L1, and V600BRAF inhibitor. Additionally, subjects may have received anti-CTLA-4 as a single agent or in combination with anti-PD-1/PD-L1, or MEK inhibitor (in combination with V600BRAF inhibitor or as a single agent), irrespective of the sequence. No additional systemic treatment is allowed for advanced or metastatic melanoma . A maximum of three prior lines of systemic therapies for unresectable or metastatic melanoma are allowed.
The last dose of prior therapy must have been received more than 4 weeks (for anti- PD-1, anti-PD-L1 or anti-CTLA-4) or more than 2 weeks (for V600BRAF or MEK inhibitor) prior to randomization.
•All subjects (with V600BRAF wild-type disease and with V600BRAF mutant disease) must have documented disease progression as per RECIST v1.1 while on/after the last therapy received prior to study entry and while on/after treatment with anti-PD1/PD-L1. The last progression must have occured within 12 weeks prior to randomization in the study.
•ECOG performance status 0-2
•At least one measurable lesion per RECIST v1.1
•At least one lesion, suitable for sequential mandatory tumor biopsies (screening and on-treatment) in accordance with the biopsy guidelines specified in protocol. The same lesion must be biopsied sequentially.
•Screening tumor biopsy must fulfill the tissue quality criteria outlined in the protocol, as assessed by a local pathologist
Key inclusion criteria for Arm 1A:
•Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma according to AJCC Edition 8
•Previously treated for unresectable or metastatic melanoma
•ECOG performance status 0-1
•At least one measurable lesion per RECIST v1.1
•Subjects must have baseline tumor sample that is positive for LAG-3 per central assessment
Other inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion Criteria

•Subjects with uveal or mucosal melanoma
•Presence of clinically active or unstable brain metastasis at time of screening.
•Use of any live vaccines against infectious diseases within 3 months before randomization/enrolment.
•Active infection requiring systemic antibiotic therapy at time of randomization/enrolment.
•Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive médications within 14 days of
randomization/enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
•Active, known or suspected autoimmune disease or a documented history of autoimmune disease.
•Prior allogenic bone marrow or solid organ transplant
•History of known hypersensitivity to any of the investigational drugs used in this study
•Prior systemic therapy for unresectable or metastatic melanoma with any investigational agent, or with any other agent except anti-PD-1/PD-L1 and anti-CTLA-4 (and V600BRAF and MEK inhibitors if subject has V600BRAF mutant disease). Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months before the start of the study treatment
•Medical history or current diagnosis of myocarditis
•Cardiac Troponin T (or Troponin I) level > 2 x ULN at screening
Other exclusion criteria may apply.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified