Advanced Cancer
Conditions
Interventions
The current study is a first-in-human (FIH) study with DCC-2618. The study will
consist of an Escalation Phase assessing increasing doses of single agent
DCC-2618 in patients with advanced malignanc
Sponsors
Deciphera Pharmaceuticals, LLC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria Patients must meet the following criteria to be eligible to enroll in the study: 1. Patients must have histologically confirmed solid tumors or hematologic malignancies. Eligible patients include the following: a. GIST patients must have a KIT or PDGFRA mutation and must have progressed on or had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients with a pre-existing resistance mutation to an approved line of therapy are eligible. For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V. b. Systemic mastocytosis (SM) patients must have a confirmed diagnosis (confirmed by a central independent pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria for SM (15) and must have documented KIT mutant disease. Patients with imatinib-sensitive KIT mutations must have progressed on or were intolerant to a tyrosine kinase inhibitor. Patients with advanced SM must present with at least 1 eligible C Finding (organ damage) as outlined in Table 3 of the 2013 International Working Group Myeloproliferative Neoplasms Research and Treatment (IWG MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5); please see below for MCL exception. Advanced SM includes: i. Aggressive SM (ASM), ii. SM-AHN, wherein the AHN does not require immediate alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include: low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, unclassifiable MDS, and HES/CEL. iii. MCL • Patients with histopathologically-confirmed MCL without a C finding are eligible. iv. Symptomatic SSM By definition, SSM patients must have at least 2 B-findings, and clinically significant symptom burden (eg, flushing, diarrhea, etc.) despite maximal treatment with approved agents to treat mediator symptoms, such as antihistamines and cromolyn sodium. v. Patients with hematologic malignancies featuring clonal expansion of eosinophils driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis confirmed by a central independent pathologist and are eligible if they have progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are eligible without prior imatinib therapy. c. Malignant glioma patients with genomic alterations potentially conferring sensitivity to DCC 2618 including, but not limited to, amplification and/or mutations of PDGFRA and/or KIT. i. Patients must not require use of enzyme-inducing antiepileptic drugs ii. Patients that require steroids must be on a stable dose for 2 weeks prior to the first dose of study drug. d. Other solid tumor patients that have alterations in genes encoding kinases that are targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2. Patients must have received approved treatments known to provide clinical benefit prior to study entry. e. Melanoma patients with mutations and/or amplification potentially conferring sensitivity to DCC-2618 including KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2 (KDR). i. Patients must have a h
Exclusion criteria
Exclusion criteria: Exclusion Criteria Patients meeting any of the following criteria will be excluded from the study: 1. GIST patients with wild type or unknown KIT or PDGFRA status 2. Patients with SM or other hematologic malignancies will be excluded if the following apply: a) SM patients with neutropenia accompanied by fever or infection, or thrombocytopenia associated with clinically significant bleeding. • Patients with an infection that is well controlled with antibiotics are eligible if there is an immediate need for treatment b) SM-AHN patients diagnosed with: i. SM with MDS (SM-MDS) who require treatment. ii. Patients requiring immediate treatment for AHN. c) Patients with leukemias, with the exception of MCL and CEL, that have progressed after imatinib. d) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a known target of DCC-2618. This includes, but is not limited to, fusions/mutations of fibroblast growth factor receptor 1 (FGFR1), Janus kinase 2 (JAK2), and Abelson murine leukemia viral oncogene (ABL). 3. Prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of DCC-2618. Patients receiving adjuvant cancer treatment are not eligible if those medications are potentially active against GIST or excluded per protocol. 4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to the administration of study drug, with the exception of hydroxyurea that is allowed to control white blood cell count. For prior therapies with a half-life longer than 3 days, the interval must be at least 28 days prior to the first administration of study drug. 5. New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure. 6. Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before start of study drug. 7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) within the 3 months before start of study drug. Patients with venous thrombotic events >=3 months before start of study drug on stable anticoagulation therapy are eligible. 8. Baseline prolongation of the rate-corrected QT interval based on repeated demonstration of QTcF >450 ms in males or >470 ms in females or history of long QT syndrome. 9. LVEF 4 weeks prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence. 11. Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks. 12. Malabsorption syndrome or other illness that could affect oral absorption. 13. Known human immunodeficiency vir
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Escalation Phase: The primary objectives are to: • Determine the safety and tolerability of oral DCC-2618 • Determine a maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of oral DCC-2618 Expansion Phase: The primary objectives are to: • Further evaluate the safety and tolerability of oral DCC-2618 • Determine the antitumor activity of DCC-2618 in all diseases under study | — |
Secondary
| Measure | Time frame |
|---|---|
| Escalation Phase: The secondary objectives are to: • Determine the pharmacokinetic (PK) profile of oral DCC-2618 • Document preliminary evidence of DCC-2618 antitumor activity Expansion Phase: The secondary objectives are to: • Determine the PK, including population PK, profile of oral DCC-2618 • Evaluate the safety and tolerability of the RP2D of oral DCC-2618 in a cohort of patients with moderate to severe renal impairment • Determine allele fraction of KIT and PDGFRA mutations in plasma cfDNA and compare it with mutation allele fraction in GIST tumor tissue and their association with prior treatment and study drug response | — |
Countries
Netherlands
Outcome results
None listed