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-DE
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-05-17
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 195

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:
- All subjects must have received anti-PD-1 checkpoint inhibitor
therapy (ie. pembrolizumab or nivolumab) either as monotherapy or in combination with ipilimumab as the last systemic therapy prior to
enrollment and must have confirmed disease progression as per RECIST v1.1 (confirmed on a subsequent scan, which can be the scan performed during screening) while on or after this therapy prior to enrollment.
- Subjects with V600BRAF wild-type disease must have received no
more than 2 prior systemic therapies including prior anti-PD-1/PD-L1
(as monotherapy or in combination with ipilimumab)
- Subjects with V600BRAF mutant disease must have received no more
than 3 prior systemic therapies including anti-PD-1/PD-L1 (as
monotherapy or in combination with ipilimumab), and V600BRAF
inhibitor (as monotherapy or in combination with a MEK inhibitor)
- The last dose of anti-PD-1 based therapy must ha

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/PDL1 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