A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands

  • STATUS
    Recruiting
  • End date
    Nov 23, 2023
  • participants needed
    185
  • sponsor
    Novartis Pharmaceuticals
Updated on 23 September 2022
cancer
systemic therapy
melanoma skin
BRAF
metastasis
pancreatic adenocarcinoma
pdr001
adenocarcinoma
mek inhibitor
squamous cell carcinoma of head and neck
immunomodulator
immunomodulators
immunologic adjuvant
malignant melanoma of skin

Summary

The primary purpose of this study is to find the recommended dose of LGK974 as a single agent and in combination with PDR001 that can be safely given to adult patients with selected solid malignancies that have progressed despite standard therapy or for which no effective standard therapy exists

Description

This open-label multicenter phase 1 dose escalation study will be the first to administer LGK974 as a single agent or in combination with PDR001 in humans.

The study will comprise of 2 parts: a dose escalation of LGK974 as a single agent, followed by a safety expansion in specific disease indications; and a dose escalation of LGK974 in combination with PDR001, followed by a safety expansion in cutaneous melanoma.

Details
Condition Pancreatic Cancer, BRAF Mutant Colorectal Cancer, Melanoma, Triple Negative Breast Cancer, Head and Neck Squamous Cell Cancer, Cervical Squamous Cell Cancer, Esophageal Squamous Cell Cancer, Lung Squamous Cell Cancer
Treatment PDR001, LGK974
Clinical Study IdentifierNCT01351103
SponsorNovartis Pharmaceuticals
Last Modified on23 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Diagnosis of locally advanced or metastatic cancer that has progressed despite standard
therapy or for which no effective standard therapy exists and histological confirmation of
one of the following diseases indicated below
Single Agent Dose escalation part:documented B-RAF mutant colorectal cancer or pancreatic
adenocarcinoma. In addition, tumors of any histological origin with documented genetic
alterations upstream in the Wnt signaling pathway are eligible with prior agreement with
Novartis
eligible with prior agreement with Novartis
Single Agent Dose expansion part: documented B-RAF mutant colorectal cancer with documented
RNF43 mutation and/or RSPO fusion or pancreatic adenocarcinoma with documented RNF43
mutation. In addition, patients with tumors of any histological origin with documented
genetic alterations upstream in the Wnt signaling pathway (e.g. RNF43 or RSPO fusion) are
LGK974 with PDR001: Dose escalation: patients with the following cancers that were
previously treated with anti-PD-1 therapy and whose best response on that therapy was
progressive disease (i.e. primary refractory): melanoma, lung SCC, HNSCC. Patients with
esophageal SCC, cervical SCC or TNBC who are either naïve or primary refractory to prior
anti-PD-1 therapy
LGK974 with PDR001: Dose expansion: patients with
cutaneous melanoma that was primary refractory to prior anti-PD-1 therapy, defined as
a best response of progressive disease or stable disease for <= 4 months, or disease
recurrence with the first 6 months of adjuvant therapy. Patients with BRAF V600-mutant
melanoma must have also received and been failed by prior systemic therapy with BRAF
V600 inhibitor, with or without a MEK inhibitor
Cutaneous melanoma with acquired resistance to prior anti-PD-1 therapy, defined as
progressive disease following response (PR or CR) or following stable disease for > 4
months. Patients with BRAF V600-mutant melanoma must have also received and been
failed by prior systemic therapy with a BRAF V600 inhibitor, with or without a MEK
inhibitor

Exclusion Criteria

Impaired cardiac function
Brain metastases that have not been adequately treated
Malignant disease other than that being treated in this study
Laboratory abnormalities as specified in the protocol
Osteoporosis, osteopenia
Bone fractures within the past year
Pathologic bone fracture
Other protocol-defined inclusion/exclusion criteria may apply
Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of LGK974 (e.g., ulcerative diseases, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
Active, known or suspected autoimmune disease or severe hypersensitivity reactions to
other monoclonal antibodies
Clear my responses

How to participate?

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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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