Clinical Trial 23116

• Overview

  Study Title:

  IDE196 (Darovasertib) In Combination with Crizotinib Versus Investigators Choice of Treatment as First-Line Therapy In HLA-A2 Negative Metastatic Uveal Melanoma (Dar-Um-2)

  Objective:

  Primary Objectives To compare IDE196 + crizotinib to investigator s choice of treatment with respect to RECIST 1.1 as assessed by BICR To compare IDE196 + crizotinib to investigator s choice of treatment with respect to OS Secondary Objectives To evaluate the safety and tolerability of IDE196 in combination with crizotinib To assess optimal dose of IDE196 + crizotinib combination To compare IDE196 + crizotinib to investigator s choice of treatment with respect to PFS per RECIST 1.1 as assessed by Investigator To compare IDE196 + crizotinib to investigator s choice of treatment with respect to objective response and duration per RECIST 1.1 as assessed by BICR and Investigator assessment Change from baseline over time and between treatment strategies in EORTC QLQ-C30 and EuroQoL (EQ)-5D-5L scores

• Treatments

  Therapies:

  Immunotherapy; Therapy (NOS)

  Medications:

  BMS-936558 (Nivolumab); Crizotinib (); IDE196 (); Ipilimumab (); Nivolumab (Opdivo); Pembrolizumab (Keytruda); Xalkori (Crizotinib); Yervoy (Ipilimumab)

• Inclusion Criteria

  Inclusion Criteria:
  • Must be at least 18 years of age.
  • Is able to provide written, informed consent before initiation of any study related procedures, and is able, in the opinion of the Investigator, to comply with all the requirements of the study.
  • Has histological or cytological confirmed UM with metastatic disease.
  • HLA-A*02:01 negative.
  • Has a representative archival metastatic tumor specimen in paraffin blocks with an associated pathology report or a minimum of 16 formalin-fixed paraffin embedded (FFPE) slides is mandatory. If archival tissue block is exhausted or not available, then a tissue biopsy FFPE sample is required unless a biopsy is not medically feasible. Only tissue from a surgical resection or a core needle, punch, or excisional/incisional biopsy sample collection will be accepted. Fine needle aspiration (FNA) samples are not acceptable.
  • Has measurable disease per RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 10 mm with computer tomography (CT) or magnetic resonance imaging (MRI) scan. An enlarged lymph node must be greater than or equal to 15 mm in short axis to be a measurable lesion.
  • Able to be safely administered and absorb study therapy.
  • Has ECOG performance status 0 or 1.
  • Has a life expectancy of at least 3 months.
  • Has adequate organ function as defined by the protocol.
  • Women of childbearing potential who are sexually active with a non-sterilized male partner, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during study treatment (see Appendix 5, Section 14.5), and must agree to continue using such precautions for 6 months after the final dose of study treatment; cessation of birth control after this point should be discussed with a responsible physician. Highly effective methods of contraception are described in Appendix 5, Section 14.5.
  • Male participants must be surgically sterile or must agree to use double barrier contraception methods from enrollment through treatment and for 6 months following administration of the last dose of study treatment.
  • Additional criteria may apply

• Exclusion Criteria

  Exclusion Criteria:
  • Has received previous treatment with a PKC inhibitor (including prior treatment with IDE196), an inhibitor directly targeting MET, or an inhibitor directly targeting GNAQ/11.
  • Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
  • Has AEs from prior anti-cancer therapy that have not resolved to Grade 0-1 except for alopecia or anemia: A) Any ongoing diarrhea requires discussion with the Sponsor Medical Monitor. B) Endocrinopathies resulting from previous immunotherapy are considered part of medical history and not an AE. C) Stable Grade 2 neuropathy is allowed.
  • Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids within the prior 3 weeks to study Day 1. Participants with brain metastases are eligible if lesions have been treated with localized therapy and there is no evidence of progression for at least 4 weeks by MRI prior to the first dose of study drug.
  • Known acquired immunodeficiency syndrome (AIDS)-related illness.
  • Active adrenal insufficiency (eg. not stable on replacement therapy), active colitis, or active inflammatory bowel disease.
  • History of interstitial lung disease, active pneumonitis, or history of pneumonitis from prior therapies requiring corticosteroid treatment. However, history of grade 1 only pneumonitis OR prior radiation pneumonitis can be discussed with the Medical Monitor for consideration of inclusion.
  • History of syncope (except due to an acute medical condition [eg, hemorrhage] that is not likely to reoccur and with permission of the medical monitor) within 6 months of the first dose of study treatment. Any history of potential syncope should be clarified and verified if possible. All participants with prior history of syncope should be discussed with the Sponsor Medical Monitor.
  • Active infection requiring systemic antibiotic therapy. Participants requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of study drug.
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol. Testing for HBV or HCV status is not necessary unless clinically indicated or the participant has a history of HBV or HCV infection.
  • Major surgery within 2 weeks of the first dose of study drug (minimally invasive procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary).
  • Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass.
  • Use of hematopoietic colony-stimulating factors (CSF) (eg, granulocyte [G]-CSF, granulocyte-macrophage [GM]-CSF, macrophage [M]-CSF) within2 weeks prior to start of study drug. An erythroid-stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the participant is not red blood cell transfusion dependent.
  • Has congestive heart failure requiring treatment. For New York Heart Association Class 1, inclusion can be considered with discussion and agreement with the Medical Monitor
  • Additional criteria may apply

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