Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion

Description

Summary

The primary purpose of this study is to evaluate the efficacy of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma

Official Title

A Randomized, Open-label, Phase II Open Platform Study Evaluating the Efficacy and Safety of Novel Spartalizumab (PDR001) Combinations in Previously Treated Unresectable or Metastatic Melanoma

Keywords

Melanoma Unresectable metastatic melanoma advanced melanoma spartalizumab PDR001 LAG525 capmatinib INC280 canakinumab ACZ885 ribociclib LEE011 immunotherapy platform study Antibodies, Monoclonal LAG525 + Spartalizumab (PDR001) Capmatinib (INC280) and Spartalizumab (PDR001) Canakinumab and Spartalizumab (PDR001) Ribociclib (LEE011) and Spartalizumab (PDR001)

Eligibility

For people ages 18 years and up

Key inclusion criteria:

  • 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 systemic therapy 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 exclusion criteria common to all combination arms:

  • Subjects with uveal or mucosal melanoma
  • Presence of clinically active or unstable brain metastasis at time of screening. Note: Subjects with previously unstable brain lesions who have been definitively treated with stereotactic radiation therapy, surgery or gamma knife therapy are eligible.
  • Subjects with brain lesions who are untreated (i.e. newly discovered brain lesions during screening) or received whole brain radiation must have documented stable disease as assessed by two consecutive assessments ≥ 4 weeks apart and have not required steroids for at least ≥ 4 weeks prior to randomization.
  • Use of any live vaccines against infectious diseases within 3 months before randomization.
  • Active infection requiring systemic antibiotic therapy at time of randomization.
  • Systemic chronic steroid therapy (˃ 10mg/day prednisone or equivalent) or any other immunosuppressive therapy administered within 7 days prior to randomization. Note: Local steroids such as topical, inhaled, nasal and ophthalmic steroids are allowed.
  • Active, known or suspected autoimmune disease or a documented history of autoimmune disease. Note: Subjects with vitiligo, controlled type I diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted.
  • 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 other agent except anti-PD-1/PD-L1 and anti-CTLA-4 (and V600BRAF and MEK inhibitors if subject has V600BRAF mutant disease).
  • Medical history or current diagnosis of myocarditis
  • Cardiac Troponin T (or Troponin I) level > 2 x ULN at screening

Locations

  • UCSF Medical Center accepting new patients
    San Francisco California 94143 United States
  • The Angeles Clinic and Research Institute accepting new patients
    Los Angeles California 90025 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT03484923
Phase
Phase 2
Study Type
Interventional
Last Updated